Vibrational studies of Thyroxine hormone: Comparative study with quantum chemical calculations

Accepted Manuscript Vibrational studies of Thyroxine hormone: Comparative study with quantum Chemical calculations

Mukunda Madhab Borah, Th.Gomti Devi PII:

S0022-2860(17)30996-1

DOI:

10.1016/j.molstruc.2017.07.063

Reference:

MOLSTR 24090

To appear in:

Journal of Molecular Structure

Received Date:

02 April 2017

Revised Date:

14 July 2017

Accepted Date:

20 July 2017

Please cite this article as: Mukunda Madhab Borah, Th.Gomti Devi, Vibrational studies of Thyroxine hormone: Comparative study with quantum Chemical calculations, Journal of Molecular Structure (2017), doi: 10.1016/j.molstruc.2017.07.063

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Raman and IR technique have been used to study the vibrational wave numbers. All the normal modes have been assigned and the scaled theoretical results found to be in a good agreement with the experimental findings. HOMOLUMO energy gap is also calculated in order to study the electrical properties of the biomolecule. The study is extended to calculate . the Natural Bond Orbital and different thermo-dynamical parameters.

ACCEPTED MANUSCRIPT Vibrational studies of Thyroxine hormone: Comparative study with quantum Chemical calculations Mukunda Madhab Borah and Th. Gomti Devi*

Molecular structure of Thyroxine

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Vibrational studies of Thyroxine hormone: Comparative study with quantum Chemical calculations Mukunda Madhab Borah and Th. Gomti Devi* Department of Physics North Eastern Regional Institute of Science and Technology Arunachal Pradesh, India-791109 Email: [email protected] Abstract: The FTIR and Raman techniques have been used to record spectra of Thyroxine. The stable geometrical parameters and vibrational wave numbers were calculated based on potential energy distribution (PED) using vibrational energy distribution analysis (VEDA) program. The vibrational energies are assigned to monomer, chain dimer and cyclic dimers of this molecule using the basis set B3LYP/LANL2DZ. The computational scaled frequencies are in good agreements with the experimental results. The study is extended to calculate the HOMO-LUMO energy gap, Molecular Electrostatic Potential (MEP) surface, hardness (η), chemical potential (μ), Global electrophilicity index (ω) and different thermo dynamical properties of Thyroxine in different states. The calculated HOMO-LUMO energies show the charge transfer occurs within the molecule. The calculated Natural bond orbital (NBO) analysis confirms the presence of intramolecular charge transfer as well as the hydrogen bonding interaction.

Keywords: Raman, FTIR, ab-initio, Thyroxine, PED, VEDA.

* Corresponding author. Tel: +91-360-2257401(extn.7056), fax: +91-360-2244307 E-mail:[email protected]

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1. Introduction: Thyroxin is one of the major hormones secreted by the thyroid gland. Disorders of the thyroid gland leads to severe mental disturbances such as depression, mood swings mental retardation etc. Thyroxine hormones have been used as an effective adjunct treatment for such disorders for the last decades [1-2]. Furthermore, thyroid hormones are essential for the development and maturation of the human brain and responsible for the synthesis of key enzymes required for neurotransmitter synthesis [3]. Thyroid hormones are produced by the thyroid gland in the presence of iodine and it is responsible for regulation of metabolism. The deficiency of iodine leads to decreased of the production of triiodothyronine (T3) and thyroxine (T4) and enlarges the thyroid tissue and causes simple goitre. Hyperthyroidism is the disease which is caused by the excessive secretion of thyroxin in the body while the deficient secretion of it is called hypothyroidism. L-Thyroxine is used to treat hypothyroidism. Hence it is necessary to have a detailed study of Thyroxine hormone so as to understand the properties and functionality of this molecule. However, there has been limited investigation of the thyroid system and they still remain a bit of mystery in functionality of this molecule. It is necessary to have a detailed spectroscopic study of this biomolecule to insight about its structural, vibrational and electrical properties. Various researchers have worked on different important bio-molecules [4-9]. R.M.S. Alvarez and et al. [4] record the FTIR spectrum as well as Raman spectra in the frequency range 150-4000 cm-1 of Thyroxine (T4), Phosphatidycholine (PC) and their mixtures. They had found that the modes localized in the aromatic β-ring and in the ether group as well as the C-I stretching modes of ring α was affected upon lipid interactions which indicate the

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interaction of Thyroxine with the Phosphatidycholine bilayer via penetration of the hydrophobic part of the molecule. The comparative analysis of IR and Raman spectra of 3, 5, 3/- triiodo-L Thyronine, 3,5 diiodo- L Thyronine and Throxine by R.M.S. Alvarez and et al. [5] in the crystalline state showed that the aromatic ring vibrations give rise to four medium and strong Raman bands in between 1530-1620 cm-1. All the 99 normal modes of vibrations are Raman and IR active in these three molecules. They obtained a strong and complex signal originates around 1600 cm-1 due to the vibrations of the (NH3+) and (CO2)- group whereas no C=O stretching band of protonated carboxyl groups could be detected. In this report, we have investigated the structural properties of biomolecule by using Raman and FTIR techniques. In order to correlate the experimental data, we have optimized Thyroxine at B3LYP/LANL2DZ level of theory using DFT method. Vibrational frequency assignments were carried out by using this method with a high degree of correlation with experimental data. 2. Materials and Methods: 2.1 Experimental: The materials are purchased from Sigma Aldrich, USA. The FTIR spectra of Thyroxine molecule with KBr were recorded in the region 4000-400 cm-1 by the thin pellet technique [10-12] with the Shimadzu IR affinity-1 spectrophotometer. The experimental Raman spectra of the sample were recorded using Horiba XPlora1 Micro-Raman system and 785 nm was used as the excitation source. 2.2 Computational methods:

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The theoretical calculation is performed by using Gaussian 09W software with the basis set B3LYP/ LANL2DZ, which is suitable for transition material. The theoretical frequencies are associated with some systematic error due to insufficient consideration of electron-correlation effects and the neglect of anharmonicity [13]. This error can be eliminated by multiplying the calculated frequency with scaling factor. The calculated vibrational frequencies are scaled by using the scaling factor 0.961 [14]. The vibrational frequency assignments of molecules are carried out by visualizing the movement of atoms in Gauss view Software and Potential Energy Distribution (PED) analysis [15-17]. The PED analysis is more accurate and enables to quantitatively describe the contribution of movement of a given group of atoms in a normal mode. The PED analysis require the construction of set of 3N-6 linearly independent internal coordinates, which represents stretching, in plane bending, out of plane bending and deformation motions of the functional groups or the chosen fragments of the molecule. The PED analysis is strongly depended on the introduced set of local coordinates. VEDA program [18] reads the input data automatically from the Gaussian program output files. Then, VEDA automatically proposes an introductory set of local mode coordinates and provides the contribution of PED. 3. Results and discussion: 3.1 Molecular Geometry: The optimized geometrical structure of Thyroxine monomer, chain dimer and cyclic dimers are calculated by DFT method with the basis set B3LYP/LANL2DZ and are shown in the fig.1a, fig.1b and fig.1c respectively. The calculated bond lengths of Thyroxine monomer, chain dimer and cyclic dimer are given in table 1a, table 1b and table 1c; while the bond angles

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are presented in table 2a, table2b and table2c respectively. Here the experimental bond lengths of Thyroxine and. 3,5,3/-triiodo-L-thyronine calculated by A. Camerman and et al. [19] were compared with the calculated bond lengths of Thyroxine monomer and shown in table 1a. The calculated C-C bond length in the benzene rings is found in between 1.401.42Å. The corresponding average experimental value of the C-C phenyl bond length is 1.40Å [19]. The C-C bond lengths in the side chain are calculated at 1.52-1.57Å in monomer, chain dimers well as cyclic dimer. The experimental side bond length of C9-C24, C24-C27 and C27C32 are found to be 1.52Å, 1.56Å and 1.54Å respectively [19]. The C-H bond lengths in the aromatic rings are calculated at about 1.08Å, whereas the C-H aliphatic bond length is found about 1.09-1.10Å, which are in good agreements with the earlier findings [20]. The C-I bond lengths are found in between 2.13-2.15Å, while in the earlier reported XRD data its average value is found to be 2.11Å [19]. The C-O bond length in monomer state is found in the range 1.39-1.41Å. The average phenyl C-O bond lengths in the XRD data have an average value of 1.41Å. All the C-O bond lengths in chain dimer are found in the same range as monomer except C32-O34 bond length, which is found to be 1.37Å. In cyclic dimer, it is calculated in the same range as monomer except C32-O34 and C67-O69 in the range 1.34Å owing to hydrogen bond interaction. The C=O bond length in monomer is found to be 1.24Å. In chain dimer the bond length of C32=O33 and C67=O68 are found to be 1.25Å and 1.24Å respectively, while in cyclic dimer it appears at 1.27Å. In the reported experimental data, the C=O bond length is found to be 1.24Å [19]]. The shift is due to the influence of intermolecular hydrogen bond in dimer molecules. The C-N bond length is obtained at 1.46-1.47Å. The C-N bond length is observed at 1.52Å [19] in the experimental values. Similarly the O-H bond length in monomer and chain dimer is found in between 0.98-1.00Å. In cyclic dimer it is calculated in between 0.98-1.04Å.

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The N-H bond lengths are calculated at 1.02Å in all the three states. All the calculated bond lengths are found to be coincident with the values found in literature [21-23]. In the interacting chain dimer, the hydrogen bond of the type O33----H58 and O57---H35 are found to be 1.88Å and 1.76Å respectively. In cyclic dimer, O33---H70 and O68---H35 bond lengths are at 1.53Å. The C-C-C inner bond angles in the ring are found to be about 1190 and the C-C-H and C-C-I outer bond angles in the rings are calculated same as C-C-C inner bond angles. The CC-N bond angle is calculated in between 1110-1130. These are close to the value found in literature [24-25]. 3.2 Frontier Molecular Orbital Analysis: The frontier molecular orbital i.e. Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are the main orbital taking part in chemical reaction [26]. It is an important concept in chemistry and molecular orbital theory is employed extensively to describe chemical behavior and stability of the molecules [27-28]. These can provide the nature of reactivity, structural and physical properties of the molecule [29-30]. A molecule with the higher value of highest occupied molecular orbital (HOMO) has a tendency to denote electrons to an acceptor molecule with lowest unoccupied molecular orbital [31-32]. The HOMO is π nature and localized within the ring, while LUMO is of π* nature is delocalized over the entire part of the molecule. Molecules with the large HOMO-LUMO gaps means a hard molecule and those with small HOMO-LUMO gaps are soft molecule [33]. The stability of a molecule can relate with its hardness. A molecule with less HOMO-LUMO gap is more reactive and the soft molecules are more polarizable than the hard ones because they need small energy

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for excitation [34]. Owing to the above reasons, the stability of a molecule can be affected by the factors of total energy, dipole moment and also the energy gap between HOMO-LUMO levels. The frontier molecular orbitals of Thyroxine monomer, chain dimer and cyclic dimers are given in fig.2a, fig.2b and fig.2c respectively. The HOMO energies, LUMO energies, hardness (η), chemical potential (μ), Global electro-philicity index (ω), Ionization energy (IE) and electron affinity (EA) of Thyroxine in all the three states are shown in table 3. The calculated HOMO-LUMO energy gap of the title molecule is 4.435 eV in the monomer state, whereas in chain dimer and cyclic dimer the corresponding value is 4.299eV and 4.408eV respectively. This reduced value in energy gap is due to chemical activity and the eventual charge transfer taking place within the molecule, which influences the biological activity of the molecule. 3.3 Molecular electrostatic potential: The Molecular Electrostatic Potential (MEP) surface provides a three dimensional visual method to understand the relative polarity of molecules [35]. MEP represents a point in the space around the molecule to provide an indication of net electrostatic effect produced at that point by total charge distribution of the molecule and correlates with dipole moments, chemical reactivity, electronegativity, partial charges etc. It is used to predict the behavior and reactivity of the molecules. MEP is very useful for the qualitative interpretation of the electrophilic and nucleophilic reactions for the study of biological recognition process and hydrogen bonding interactions [36]. The different values of the electrostatic potential on the surface of the molecule are represented by different colors. The red color indicates the region of most negative electrostatic potential, whereas the blue one indicates positive electrostatic potential and the yellow shows slightly electron rich region respectively. The green color represents the neutral

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site [37-39]. The MEP surface of Thyroxine monomer is presented in fig.3. We are getting green color of this molecule in different associated states which shows that this is a pure neutral molecule. 3.4 NBO analysis: The NBO analysis provides the detailed understanding of the nature of electronic conjugation between the bonds in molecule. It is a useful method for analyzing hybridization, conjugative interactions, covalency effects, H-bonding [40], Van Der Waals interactions and electron density transfer from filled lone pair orbital of one sub system and vacant orbital of another sub system [20]. The DFT method is used to probe the various second order interaction between the filled orbitals of one subsystem and empty orbitals of another subsystem [41-43]. The filled orbital corresponds to the Lewis structure while the unfilled orbital corresponds to non- Lewis structure and interaction between them measure the delocalization due to inter and intra-molecular interaction. The second order Fock matrix were carried out to evaluate the donor–acceptor interactions in the NBO analysis [45]. For each donor (i) and acceptor (j), the stabilization energy E(2) associated with the delocalization i→ j is estimated [44-45] as

E

( 2)

F (i, j ) 2  Eij  qi  j  i

Where qi is the donor orbital occupancy, i and j diagonal elements and F(i,j) is the off diagonal NBO Fock-matrix element. The larger value of E(2) indicates the more intense interaction between the electron donors and acceptor groups with greater extent to conjugate of the whole system. The larger the stabilization energy, the more is the stabilization of the molecule [20].

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In the present work, we have analyzed some of the electron donor orbital and electron acceptor orbital and the interacting stabilization energy by utilizing the second order perturbation analysis of Fock matrix. The various donor acceptor interactions with their stabilization energy for monomer, chain dimer and cyclic dimer are determined and listed in Table 4. Hyper conjugative interactions are formed by overlapping between the bonding σ and anti-bonding σ* as well as bonding π and anti-bonding π* orbitals of the ring, it causes intramolecular charge transfer (ICT) that stabilizes the molecular system [46]. A strong interaction has been observed between the lone electron pair of N29 and the neighbor σ*(C27-C32) anti-bonding orbital. The interaction between lone pair O33 and σ*(C27-C32), σ*(C32-O34) anti bonding orbital is very strong with the stabilization energy 15.85 kJ/mole and 34.32 kJ/mole respectively. The intermolecular interaction is formed because of the overlapping of the orbitals between the (C-C), (C-I), (C-O), (C-N) and (O-H) bonding and antibonding orbitals, which result the intra-molecular charge transfer and stabilization of the molecular system. From table 4 it can be clearly observed that there is a strong delocalization in electron density of the order 1.9e for conjugated single as well as double bond of Thyroxine molecule. The intra-molecular hyper conjugative interactions of σ (C1-C2) with σ*(C1-C6), σ*(C2-C3) leading to stabilization of 2kJ/mol. The conjugation of π (C9-C10) with the antibonding π*(C11-C12) and π*(C13-C14) are associated with a strong delocalization of 23.35 kJ/mole and 22.69 kJ/mole respectively. For the dimer states the second order perturbation analysis shows conjugation of lone pair with the anti-bonding orbitals. These interactions stabilize the chain as well as cyclic dimer.

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3.5 Mulliken charges: The calculation of Mulliken atomic charges has an important role in the application of quantum chemical calculations of molecular system. The Mulliken analysis is performed by default in Gaussian [47]. The calculation of atomic charges are involved a direct partitioning of the molecular wave function into atomic contributions following some arbitrary, orbital-based scheme proposed by Mulliken [48]. The atomic charges affect many properties such as dipole moment, electronic structure and polarizability of a molecule [49]. The charge distribution of Thyroxine monomer, chain dimer and cyclic dimer are calculated from Mulliken’s analysis at B3LYP/LANL2DZ level of theory. The calculated Mullikan’s charges for Thyroxine monomer, chain and cyclic dimers are presented in table 5. The result shows that the carbon atomic charges are to be found either positive or negative. From the above results it is clear that carbon atoms attached with oxygen, nitrogen and carbon atoms are positive however the other carbon atoms have more negative charges. All the charges of hydrogen and iodine atoms have positive values. The hydrogen atoms attached with the oxygen and nitrogen atoms have more positive charges than the other hydrogen atom. The Nitrogen atom processes highest negative charge in both monomer and dimer states. All the oxygen atoms are negatively charged. The charge of the Oxygen atom associated with the C=O bond is -0.247e in the monomer state. The negative charges of the Oxygen atom associated with the C=O bond increases to -0.327e, -0.257e (chain dimer) and 0.323e, -0.323e (cyclic dimer) due to hydrogen bond formation between the dimer molecules. Similarly we are observing increase in mulliken atomic charges from monomer to dimer state in carbon atom which is due to charge transfer between fragments of molecules under interaction.

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3.6 Energy parameters: Energy and dipole moments of Thyroxine are calculated and represented in table 6 for monomer, chain dimer and cyclic dimer on the basis of DFT calculations having basis set B3LYP/LANL2DZ respectively. Dipole moment plays an important role in understanding the nature of the chemical bond. The measure of the dipole moment helps in distinguishing polar and non-polar molecules. The greater the dipole moment indicates greater in the polarity of such molecules. In our present case the dipole moment of the Thyroxine molecule in the monomer state is found to be 3.685 Debye, while in chain and cyclic dimer the corresponding values are 7.260 Debye and 1.261 Debye respectively. The less value of the dipole moment in cyclic dimer may be due to the stable arrangement of the Hydrogen bond in the structure. The zero point vibrational energy is 147.271 kCal/mole in the monomer state, while in chain and cyclic dimer this energy is 295.481 kCal/mole and 295.712kCal/mole. The self-consistent field (Hartee) energy of Thyroxine monomer, chain dimer and cyclic dimer is found to be -979.228 Hartee, 1958.479 Hartee and

-1958.493 Hartee respectively. The higher value (numerical) of energy is

observed in the dimer state due to the interaction of two monomer molecules. We have also carried out binding energy calculations in the dimer states. The binding energy is the energy required to disassemble a whole molecular system into separate parts. The binding energy in the Hydrogen bonding systems can be explained by charge transfer, electrostatic effects and more partial covalent contributions. The binding (interaction) energy of Thyroxine chain dimer and cyclic dimer is found to be -14.433 kcal mol-1 and -23.218 kcal mol-1 respectively. We have observed the higher value of binding energy in the cyclic dimer; it may be due to the formation of strong Hydrogen bond in the cyclic dimer which stabilizes the whole system.

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3.7 Vibrational assignments: The detailed vibrational assignment of Thyroxine has been carried out with the help of normal coordinate analysis. The molecule Thyroxine has 35 atoms and possesses 99 normal modes of fundamental vibration. Each of chain dimer and cyclic dimer has 70 atoms and hence 204 normal modes of vibration. All the harmonic vibrational frequencies were calculated at B3LYP levels with LANL2DZ basis set. The experimental Raman and IR frequencies along with the theoretical wavenumbers for monomer, chain dimer and cyclic dimer are presented in table7a, table7b and table7c respectively. Comparison between the calculated and the observed vibrational spectra helps to understand the observed spectral features of the molecule. The theoretical and experimental Raman and IR spectra of Thyroxine are shown in fig. 4 and fig. 5 respectively. 3.7.1 C-H vibrations: The C-H stretching vibration is observed in between 3000-3100cm-1 for the aromatic benzene ring [25, 50-54]. This is the characteristic region for the ready identification of the C–H stretching vibration. In Thyroxine monomer these are calculated at 3127.09cm-1, 3126.13cm-1, 3118.44cm-1, 3096.34cm-1, 3013.70cm-1 and 2992.55cm-1 respectively. In chain dimer the C-H stretching vibrations are calculated in between 3130.94-2993.52cm-1, while in cyclic dimer these are calculated in between 3127.63cm-1-2994.54cm-1 respectively. In the recorded Raman spectra it is observed at 3154cm-1, whereas in the IR spectra it appears at 3050cm-1, which are in good agreement with the calculated frequencies. These vibrations are contributing exactly 99%, which is evident from the PED calculations. We have calculated some

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weak aliphatic C-H stretching vibrations. This is due to the reduction of negative charge on Carbon atoms, which leads to decrease in the dipole moment [55]. In our present study the CH2 symmetric stretching is calculated at 2942.58cm-1 in monomer with 99% PED contribution. In Thyroxine chain dimer the C-H symmetric stretching is calculated at 2945.75cm-1 and 2945.13cm-1 respectively. These are calculated at 2943.33cm-1 and 2943.25cm-1 in cyclic dimer. This peak arises at 2934cm-1 in the experimental Raman spectra, while it appears at 2887cm-1 in the recorded IR spectra. The CH2 asymmetric stretching is calculated at 3013.70cm-1 and 2992.55cm-1 in monomer. While in chain and cyclic dimer these are calculated at 3013.70cm-1, 3011.77cm-1, 2995.44cm-1, 2993.52cm-1 and 3012.59cm-1, 3012.50cm-1, 2994.57cm-1, 2994.54cm-1 respectively. It appears at 3050cm-1 in the recorded IR spectra. The C-H in plane bending vibrations appears in the range 1300-1000cm-1 [56-57]. In our title molecule the C-H in plane bending vibration is recorded at 1248cm-1, 1162cm-1 and 1120cm-1 in the Raman spectrum, while in the IR spectrum it is recorded at 1230cm-1, 1180cm-1 and 1143cm-1 respectively. Both the FTIR and Raman spectrum shows good correlation with the computed wavenumbers in all the three states as shown in the tables (table7a, table7b, table7c). The out of plane bending vibrations are generally appears in the range 1000-750 cm-1 [58-60]. In our title molecule the C-H out of plane bending vibration is recorded at 970 cm-1 and 916cm-1 in the experimental Raman spectra. In the IR spectra it is observed at 979cm-1. This shows a good agreement with the theoretical calculations, where the corresponding peaks are calculated at 959.08cm-1, 913.91cm-1, 899.50cm-1, 885.08cm-1, 881.24cm-1, 878.35cm-1 and 865.86cm-1 in the monomer state. In chain dimer the C-H out of plane bending vibration is

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calculated at 967.73cm-1, 911.99cm-1, 908.14cm-1, 907.18cm-1, 905.26cm-1, 888.92cm-1, 884.12cm-1, 878.35cm-1, 872.59cm-1, 868.74cm-1 and 863.94 respectively while in the chain dimer vibrations are calculated at 964.08cm-1, 913.51cm-1, 912.98cm-1, 905.83cm-1, 905.42cm-1, 887.48cm-1, 887.46cm-1, 877.62cm-1 and 877.60cm-1 respectively. 3.7.2 Amino group (NH2) vibrations: The NH stretching vibrations are generally observed in between 3300-3500cm-1 [61-63]. The position of the absorption in this region depends upon the degree of hydrogen bonding and upon the physical state of the sample. The NH2 symmetric stretching vibration in Thyroxine is calculated at 3409.63cm-1, with 99% of the PED contribution. In the chain dimer the same vibration is assigned at 3410.59cm-1 and 3406.74cm-1 respectively. In case of cyclic dimer the NH symmetric stretching is calculated at 3411.15cm-1 and 3411.08cm-1 respectively. All these vibrations are contributing exactly 99%, as presented at the table 7. The NH asymmetric stretching vibration is assigned at 3532cm-1 with 100% of the PED value in the monomer state. In chain and cyclic dimer these are calculated at 3530.71cm-1, 3526.87cm-1 and 3531.51cm-1 and 3531.44cm-1 respectively. The NH2 in plane bending vibration is calculated at 1621.21cm-1 in Thyroxine monomer, 1631.78cm-1 and 1624.09cm-1 in chain dimer and at 1625.28cm-1 and 1625.21cm-1 in the cyclic dimer respectively. This bending vibration is observed at 1630cm-1 in the FTIR spectrum. 3.7.3 C-I vibrations: Thyroxine monomer has four Iodine atoms in the two benzene rings. In the literature the C-I stretching vibrations are found to be in between 600-485cm-1 [64-70]. The C-I

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stretching vibrations are observed in between 680-670cm-1 in Thyroxine molecule. In the theoretically calculated frequencies it appears at 680.39cm-1 and 670.78cm-1 in the monomer state. In chain dimer it is calculated at 680.41cm-1, 680.21cm-1, 674.62cm-1 and 671.74cm-1 respectively. In the cyclic dimer the C-I stretching vibration appears at 680.41cm-1, 680.35cm-1, 675.67cm-1 and 664.68cm-1 respectively. In the experimental data of Raman it is observed at 676cm-1. According to PED analysis, the vibration bands are weak of the range 10-30%. 3.7.4 COOH vibrations: Molecule containing carbonyl group shows strong absorption band of C=O stretching vibration in the region of 1850-1550 cm-1 [71]. The C=O stretching vibration in Thyroxine monomer is calculated at 1644.27cm-1. In chain dimer this stretching vibration is assigned at 1642.35cm-1 and 1603.91cm-1, while in cyclic dimer it is calculated at 1617.98cm-1 and 1606.93cm-1 respectively. The drastic change in the frequency in cyclic dimer is due to the formation of hydrogen bonding. In the experimental IR and Raman spectra, it is recorded at 1630cm-1 and 1600cm-1 respectively. The C-O stretching vibration in the Thyroxine is calculated at 1467.50cm-1, 1319.45cm-1, 1313.69cm-1, 1254.10cm-1, 1221.43cm-1 and 1152.24cm-1 respectively. In chain dimer the C-O stretching vibration appears at 1372.31cm-1, 1365.58cm-1, 1313.69cm-1, 1312.73cm-1, 1274.29cm-1, 1255.07cm-1, 1253.14cm-1, 1245.46cm-1, 1221.43cm-1, 1219.51cm-1, 1200.29cm-1, 1151.86cm-1, 1151.79cm-1 and 1041.72cm-1 respectively, while in the cyclic dimer this vibration is calculated at 1315.21cm-1, 1315.13cm-1, 1272.06cm-1, 1266.99cm-1, 1252.87cm1,

1252.85cm-1, 1220.60cm-1, 1220.53cm-1, 1220.09cm-1, 1215.05cm-1, 1199.68cm-1, 1151.71cm-

1,

1151.66cm-1, 1108.73cm-1, 1024.09cm-1 and 1024.08cm-1 respectively. In the experimental

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Raman spectrum it is assigned at 1316cm-1, 1248cm-1 and 1162cm-1 respectively. In the FTIR spectrum the C-O stretching is recorded at 1309cm-1, 1230cm-1 and 1143cm-1 respectively. This shows that the experimentally observed frequencies agree with the theoretical findings. Their vibrations are found weak according to PED analysis. The O-H stretching vibration is generally observed in between 3700-3584cm-1 (100% in PED analysis). But, the formation of intermolecular hydrogen bonding lowers this vibration to 3500-3200cm-1 [72-73]. In monomer the O-H stretching is calculated at 3509.57cm-1 and 3496.12cm-1. In chain dimer it appears at 3499.00cm-1, 3495.16cm-1, 3246.26cm-1 and 3157.85cm-1 respectively. While in cyclic dimer the same vibration is assigned at 3495.43cm-1, 3495.41cm-1, 2695.31cm-1 and 2527.15cm-1 respectively. In the experimental IR spectra, this vibration is recorded at 3471cm-1. The O-H in plane bending vibration is calculated in the same range as the C-O stretching vibration. The O-H out of plane bending vibration lies in between 751-710cm-1 [74]. All the values are given in table 7. 3.7.5 Thyroxine ring vibrations: The aromatic ring stretching vibrations are generally observed in between 16001350cm-1 [75-80]. In B3LYP theoretical calculations the C=C ring stretching’s are calculated at 1571.24-1516.46cm-1, 1423.24-1367.50cm-1 and 1313.69-1278.13cm-1 as shown in table 7a. In chain dimer the C=C absorption takes place at 1571.14-1517.03cm-1, 1423.24-1401.14cm-1, 1366.54cm-1, 1365.58cm-1, 1313.69cm-1, 1312.73cm-1 and 1299.27-1274.29cm-1, while in cyclic dimer it appears at 1571.09-1516.73cm-1, 1422.86-1401.51cm-1, 1369.44cm-1, 1367.02cm-1, 1367.00cm-1 and 1312.30-1272.06cm-1 respectively. In the recorded Raman spectra, it appears at

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1498cm-1 and 1316cm-1; while in the experimental IR spectra it is assigned at 1309cm-1 respectively. The C-C-C in plane bending vibrations give rise weak bands across the low frequency region below 1000cm-1 with the weak bands [81-82]. In our theoretical calculations the peaks are calculated at 1023.46cm-1, 1013.86cm-1, 853.37cm-1, 811.08cm-1, 788.02cm-1, 680.39cm-1 and 670.78cm-1 respectively. In chain dimer the C-C-C in plane bending vibration appears at 1023.62cm-1, 1023.47cm-1, 1014.82cm-1, 1012.89cm-1, 883.16cm-1, 882.20cm-1, 854,33cm-1, 853.37cm-1, 789.94cm-1, 711.14cm-1, 707.30cm-1, 689.04cm-1, 680.41cm-1, 680.21cm-1, 674.62cm-1 and 671.74cm-1 respectively, while it is calculated at 1024.09cm-1, 1024.08cm-1, 1013.74cm-1, 1013.73cm-1, 881.82cm-1, 881.74cm-1, 855.13cm-1, 854.92cm-1, 790.14cm-1, 789.77cm-1, 694.01cm-1, 687.26cm-1, 680.41cm-1, 680.35cm-1, 675.67cm-1 and 664.68cm-1 in the Thyroxine cyclic dimer respectively. In the experimental Raman spectra the corresponding peak appears at 806cm-1 and 686cm-1, while in the IR spectra it is assigned at 854cm-1 and 781cm-1 respectively. The out of plane bending vibration occurs at lower wavenumber side in addition to in-plane bending vibrations. All the vibrations are presented in table 7; most vibrations are of medium band (20-50% PED analysis). 4. Conclusion: The optimized geometrical structure of Thyroxine were investigated and analyzed by using B3LYP/LANL2DZ level of theory. The FTIR and Raman spectra have been recorded and vibrational assignments were presented in monomer and dimer states. Most of the peak frequencies of both the techniques are comparable, although some frequencies are missing in FTIR and Raman spectra due to their active and inactive vibrational properties.The differences

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between the observed and computed wavenumbers of different vibrations are very less. The molecular geometry, Natural Bond Orbital (NBO), thermo dynamical parameters, HOMOLUMO energy gap and other related molecular properties were also discussed and reported. The Theoretically calculated bond lengths showed excellent agreements with the previously reported XRD values. The length of the hydrogen bond in cyclic and chain dimer is also reported. The HOMO- LUMO energy difference supports the charge transfer interaction within the molecule. The second order NBO calculation shows the intra and intermolecular charge transfer in Thyroxine monomer and dimer which results the stabilization of the whole molecular system. The values of the binding energy have also been calculated in the dimer states. We have observed the higher value of binding energy in the cyclic dimer than the chain dimer due to the formation of strong Hydrogen bond in the cyclic dimer. 5. Acknowledgements: The authors are grateful to FIST- DST, Delhi for instrumentation facilities in the Department of Physics, NERIST, Arunachal Pradesh, India. One author (M.M. Borah) is thankful to DST-INSPIRE, India for Inspire fellowship during the research work.

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Figure Caption: Fig. 1a --------- Molecular structure of Thyroxine monomer Fig. 1b --------- Molecular structure of Thyroxine chain dimer Fig. 1c --------- Molecular structure of Thyroxine cyclic dimer Fig. 2a --------- Frontier molecular orbital diagram of Thyroxine monomer Fig. 2b --------- Frontier molecular orbital diagram of Thyroxine chain dimer Fig. 2c --------- Frontier molecular orbital diagram of Thyroxine cyclic dimer Fig. 3 -------- The total electron density mapped with electrostatic potential surface of Thyroxine monomer Fig.4a --------Raman spectrum of Thyroxine (0-1400cm-1) Fig.4b --------Raman spectrum of Thyroxine (1400-4000cm-1) Fig.5 --------IR spectrum of Thyroxine Table 1a ---- Calculated bond length of Thyroxine monomer Table 1b ---- Calculated bond length of Thyroxine chain dimer Table 1c ---- Calculated bond length of Thyroxine cyclic dimer Table 2a ---- Calculated bond angles of Thyroxine monomer Table 2b ---- Calculated bond angles of Thyroxine chain dimer Table 2c ---- Calculated bond angles of Thyroxine cyclic dimer Table 3 ---- Electrical parameters of Thyroxine Table 4 ---- Second Order perturbation theory analysis of Fock matrix in NBO basis for Thyroxine Table 5 ---- Mullikan’s atomic charges for optimized geometry of Thyroxine Table 6 ---- The Thermo dynamical parameter of Thyroxine

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Table 7a---- The experimental and theoretical peak frequencies of vibrational frequencies assigned for Thyroxine monomer Table 7b---- The experimental and theoretical peak frequencies of vibrational frequencies assigned for Thyroxine chain dimer Table 7c---- The experimental and theoretical peak frequencies of vibrational frequencies assigned for Thyroxine cyclic dimer

Fig. 1a

Fig. 1b

Fig. 1c.

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ELUMO = -1.796eV

LUMO

EHOMO- ELUMO=4.435eV

EHOMO =-6.231

HOMO Fig. 2a.

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ELUMO = -1.877eV

EHOMO- ELUMO=4.299eV

LUMO

EHOMO = -6.177eV

HOMO Fig. 2b.

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ELUMO = -1.850eV

EHOMO- ELUMO=4.408eV LUMO

EHOMO = -6.258eV

HOMO Fig. 2c.

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Fig. 3

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Raman Intensity/Arbitr. Unit

Thyroxine cyclic dimer(The.)

Thyroxine chain dimer (The.)

Thyroxine Monomer (The.)

Thyroxine Raman (Expt.)

200

400

600

800

1000 -1

Wavenumber/cm Fig. 4a

1200

1400

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Raman Intensity/Arbitr. Unit

Thyroxine chain dimer (The.)

Thyroxine cyclic dimer(The.)

Thyroxine Monomer (The.)

Thyroxine Raman (Expt.)

1500

2000

2500

3000 -1

Wavenumber/cm Fig. 4b

3500

4000

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Absorbance/Arbitr. Unit

Thyroxine cyclic dimer(The.)

Thyroxine Chain dimer(The.)

Thyroxine Monomer(The.)

Thyroxine IR(Expt.)

500

1000

1500

2000

2500

3000 -1

Wavenumber/cm Fig. 5

3500

4000

ACCEPTED MANUSCRIPT Highlights: > Raman band of Thyroxine was recorded by using Horiba Raman setup. > The FT-IR spectra of Thyroxine were recorded by using with KBr pellet technique. > Experimental results have been compared with the theoretical calculations. > The contribution of PED(%) were calculated by using VEDA program. > The optimized parameters, band gap, MEP, Mulliken’s charge, NBO and thermo dynamical Properties have been reported

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1aTable

Sl. No.

Bond

Bond Length(Å) DFT

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

C1-C2 C2-C3 C3-C4 C4-C5 C5-C6 C6-C1 C11-C12 C12-C13 C13-C14 C14-C9 C9-C10 C10-C11 C9-C24 C24-C27 C27-C32 C1-H7 C5-H8 C10-H15

1.40 1.41 1.42 1.40 1.40 1.40 1.41 1.41 1.40 1.41 1.41 1.41 1.52 1.56 1.53 1.08 1.08 1.09

1a

Sl. No.

Bond

XRD[19]

1.26 1.47 1.39 1.42 1.38 1.38 1.49 1.35 1.49 1.45 1.52 1.56 1.54

Bond Length(Å) DFT

19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

C14-H16 C24-H25 C24-H26 C27-H28 C2-I19 C4-I18 C11-I21 C13-I20 C3-O22 C6-O17 C12-O17 C32-O34 C32=O33 C27-N29 O22-H23 O34-H35 N29-H30 N29-H31

1.08 1.10 1.10 1.09 2.13 2.15 2.13 2.13 1.39 1.41 1.40 1.39 1.24 1.47 0.98 1.00 1.02 1.02

1a. The optimized geometrical parameter (selected bond lengths) of Thyroxine

XRD[19]

2.15 2.06 2.11 1.34 1.41 1.41 1.28 1.24 1.52

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1bTable

Sl. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Bond C1-C2 C2-C3 C3-C4 C4-C5 C5-C6 C6-C1 C11-C12 C12-C13 C13-C14 C14-C9 C9-C10 C10-C11 C9-C24 C24-C27 C27-C32 C36-C37 C37-C38 C38-C39 C39-C40 C40-C41 C41-C36 C44-C45 C45-C46 C46-C47 C47-C48

Bond Length(Å) 1.40 1.41 1.42 1.40 1.40 1.40 1.41 1.41 1.40 1.41 1.41 1.41 1.52 1.57 1.53 1.40 1.41 1.42 1.40 1.40 1.40 1.41 1.41 1.41 1.41

Sl. No. 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50

Bond C48-C49 C49-C44 C44-C59 C59-C62 C62-C67 C1-H7 C5-H8 C10-H15 C14-H16 C24-H25 C24-H26 C27-H28 C36-H42 C40-H43 C45-H50 C49-H51 C59-H60 C59-H61 C62-H63 C2-I19 C4-I18 C11-I21 C13-I20 C37-I54 C39-I53

1b Bond Length(Å) 1.40 1.41 1.52 1.57 1.54 1.08 1.08 1.09 1.08 1.10 1.10 1.09 1.08 1.08 1.09 1.08 1.10 1.10 1.10 2.13 2.15 2.13 2.13 2.13 2.14

Sl. No. 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74

Bond C46-I56 C48-I55 C3-O22 C6-O17 C12-O17 C32-O34 C32=O33 C38-O57 C41-O52 C47-O52 C67-O69 C67=O68 C27-N29 C62-N64 O22-H23 O34-H35 O57-H58 O69-H70 N29-H30 N29-H31 N64-H65 N64-H66 O33-H58 O57-H35

1b. The optimized geometrical parameter (selected bond lengths) of Thyroxine chain dimer

Bond Length(Å) 2.13 2.13 1.39 1.41 1.40 1.37 1.25 1.39 1.41 1.40 1.39 1.24 1.47 1.46 0.98 1.00 1.00 0.98 1.02 1.02 1.02 1.02 1.88 1.76

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1cTable

Sl. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Bond C1-C2 C2-C3 C3-C4 C4-C5 C5-C6 C6-C1 C11-C12 C12-C13 C13-C14 C14-C9 C9-C10 C10-C11 C9-C24 C24-C27 C27-C32 C36-C37 C37-C38 C38-C39 C39-C40 C40-C41 C41-C36 C44-C45 C45-C46 C46-C47 C47-C48

Bond Length(Å) 1.40 1.41 1.42 1.40 1.40 1.40 1.41 1.41 1.40 1.41 1.41 1.41 1.52 1.57 1.53 1.40 1.41 1.42 1.40 1.40 1.40 1.41 1.41 1.41 1.41

Sl. No. 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50

Bond C48-C49 C49-C44 C44-C59 C59-C62 C62-C67 C1-H7 C5-H8 C10-H15 C14-H16 C24-H25 C24-H26 C27-H28 C36-H42 C40-H43 C45-H50 C49-H51 C59-H60 C59-H61 C62-H63 C2-I19 C4-I18 C11-I21 C13-I20 C37-I54 C39-I53

1c Bond Length(Å) 1.40 1.41 1.52 1.57 1.53 1.08 1.08 1.09 1.08 1.10 1.10 1.09 1.08 1.08 1.09 1.08 1.10 1.10 1.09 2.13 2.15 2.13 2.13 2.13 2.15

Sl. No. 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74

Bond C46-I56 C48-I55 C3-O22 C6-O17 C12-O17 C32-O34 C32=O33 C38-O57 C41-O52 C47-O52 C67-O69 C67=O68 C27-N29 C62-N64 O22-H23 O34-H35 O57-H58 O69-H70 N29-H30 N29-H31 N64-H65 N64-H66 O33-H70 O68-H35

1c. The optimized geometrical parameter (selected bond lengths) of Thyroxine cyclic dimer

Bond Length(Å) 2.13 2.13 1.39 1.41 1.40 1.34 1.27 1.39 1.41 1.40 1.34 1.27 1.46 1.46 0.98 1.04 0.98 1.04 1.02 1.02 1.02 1.02 1.53 1.53

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2aTable

Sl. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Bond

Angle

C1-C2-C3 C2-C3-C4 C3-C4-C5 C4-C5-C6 C5-C6-C1 C6-C1-C2 C9-C10-C11 C10-C11-C12 C11-C12-C13 C12-C13-C14 C13-C14-C9 C14-C9-C10 C10-C9-C24 C14-C9-C24 C9-C24-C27 C24-C27-C32 C2-C1-H7 C6-C1-H7

121.09 118.10 121.54 118.88 121.12 119.27 120.77 120.32 118.95 120.66 120.43 118.85 119.91 121.24 113.39 108.71 120.17 120.56

Sl. No. 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

Bond C6-C5-H8 C4-C5-H8 C9-C14-H16 C13-C14-H16 C9-C10-H15 C11-C10-H15 C9-C24-H25 C9-C24-H26 C27-C24-H25 C27-C24-H26 C24-C27-H28 C32-C27-H28 C1-C2-I19 C3-C2-I19 C3-C4-I18 C5-C4-I18 C10-C11-I21 C12-C11-I21

2a Angle 119.09 122.03 118.74 120.80 119.68 119.55 109.06 110.91 108.82 107.49 108.83 105.91 119.33 119.58 119.51 118.95 119.37 120.30

Sl. No. 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54

2a. Calculated bond angles of Thyroxine monomer

Bond C12-C13-I20 C14-C13-I20 C2-C3-O22 C4-C3-O22 C1-C6-O17 C5-C6-O17 C11-C12-O17 C13-C12-O17 C27-C32=O33 C27-C32-O34 C6-O17-C12 C24-C27-N29 C32-C27-N29 C27-N29-H30 C27-N29-H31 O33=C32-O34 C3-O22-H23 C32-O34-H35

Angle 120.11 119.22 117.85 124.05 123.55 115.33 120.36 120.49 126.78 111.27 120.55 111.36 112.97 114.15 115.25 121.95 112.40 111.22

ACCEPTED MANUSCRIPT

2bTable

Sl. Bond Angle No. 1 C1-C2-C3 121.13 2 C2-C3-C4 118.09 3 C3-C4-C5 121.51 4 C4-C5-C6 118.94 5 C5-C6-C1 121.11 6 C6-C1-C2 119.22 7 C9-C10-C11 120.77 8 C10-C11-C12 120.31 9 C11-C12-C13 118.96 10 C12-C13-C14 120.63 11 C13-C14-C9 120.47 12 C14-C9-C10 118.85 13 C10-C9-C24 120.05 14 C14-C9-C24 121.10 15 C9-C24-C27 112.80 16 C24-C27-C32 107.99 17 C36-C37-C38 121.36 18 C37-C38-C39 118.25 19 C38-C39-C40 120.99 20 C39-C40-C41 119.37 21 C40-C41-C36 121.02 22 C41-C36-C37 119.01 23 C44-C45-C46 120.74 24 C45-C46-C47 120.27 25 C46-C47-C48 119.03 26 C47-C48-C49 120.60 27 C48-C49-C44 120.44 28 C49-C44-C45 118.91 29 C45-C44-C59 120.02 30 C49-C44-C59 121.07 31 C44-C59-C62 112.68 32 C59-C62-C67 108.30 33 C2-C1-H7 120.18 34 C6-C1-H7 120.60 35 C6-C5-H8 119.02 36 C4-C5-H8 122.05 37 C9-C14-H16 118.89

Sl. No. 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74

2b

Bond C13-C14-H16 C9-C10-H15 C11-C10-H15 C9-C24-H25 C9-C24-H26 C27-C24-H25 C27-C24-H26 C24-C27-H28 C32-C27-H28 C37-C36-H42 C41-C36-H42 C39-C40-H43 C41-C40-H43 C44-C45-H50 C46-C45-H50 C44-C49-H51 C48-C49-H51 C44-C59-H60 C44-C59-H61 C62-C59-H60 C62-C59-H61 C59-C62-H63 C67-C62-H63 C1-C2-I19 C3-C2-I19 C3-C4-I18 C5-C4-I18 C10-C11-I21 C12-C11-I21 C12-C13-I20 C14-C13-I20 C36-C37-I54 C38-C37-I54 C38-C39-I53 C40-C39-I53 C45-C46-I56 C47-C46-I56

Angle 120.62 119.63 119.61 109.31 110.96 108.84 107.45 108.48 106.27 120.35 120.64 121.70 118.93 119.65 119.62 118.78 120.76 109.52 110.56 108.74 107.41 107.81 107.37 119.34 119.52 119.57 118.92 119.29 120.39 120.17 119.20 118.80 119.84 120.38 118.63 119.40 120.32

2b. Calculated bond angles of Thyroxine chain dimer

Sl. No. 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110

Bond C47-C48-I55 C49-C48-I55 C2-C3-O22 C4-C3-O22 C1-C6-O17 C5-C6-O17 C11-C12-O17 C13-C12-O17 C27-C32=O33 C27-C32-O34 C6-O17-C12 C37-C38-O57 C39-C38-O57 C36-C41-O52 C40-C41-O52 C46-C47-O52 C48-C47-O52 C62-C67=O68 C62-C67-O69 C41-O52-C47 C24-C27-N29 C32-C27-N29 C59-C62-N64 C67-C62-N64 C27-N29-H30 C27-N29-H31 C62-N64-H65 C62-N64-H66 O33=C32-O34 O68=C67-O69 C3-O22-H23 C32-O34-H35 C38-O57-H58 C67-O69-H70 O33-H58-O57 O57-H35-O34

Angle 120.15 119.25 117.87 124.04 123.69 115.20 120.44 120.37 124.39 112.82 120.74 118.15 123.60 123.61 115.36 120.39 120.36 125.74 111.89 120.66 111.32 113.37 111.84 111.85 113.78 115.12 113.71 115.12 122.78 122.35 112.37 112.58 118.64 111.40 130.93 146.62

ACCEPTED MANUSCRIPT

2cTable

Sl. Bond Angle No. 1 C1-C2-C3 121.11 2 C2-C3-C4 118.08 3 C3-C4-C5 121.51 4 C4-C5-C6 118.93 5 C5-C6-C1 121.11 6 C6-C1-C2 119.25 7 C9-C10-C11 120.74 8 C10-C11-C12 120.30 9 C11-C12-C13 118.97 10 C12-C13-C14 120.65 11 C13-C14-C9 120.41 12 C14-C9-C10 118.91 13 C10-C9-C24 119.98 14 C14-C9-C24 121.11 15 C9-C24-C27 112.99 16 C24-C27-C32 107.65 17 C36-C37-C38 121.11 18 C37-C38-C39 118.08 19 C38-C39-C40 121.51 20 C39-C40-C41 118.93 21 C40-C41-C36 121.11 22 C41-C36-C37 119.25 23 C44-C45-C46 120.74 24 C45-C46-C47 120.30 25 C46-C47-C48 118.97 26 C47-C48-C49 120.65 27 C48-C49-C44 120.41 28 C49-C44-C45 118.91 29 C45-C44-C59 119.98 30 C49-C44-C59 121.11 31 C44-C59-C62 112.98 32 C59-C62-C67 107.65 33 C2-C1-H7 120.12 34 C6-C1-H7 120.63 35 C6-C5-H8 119.03 36 C4-C5-H8 122.03 37 C9-C14-H16 118.80

Sl. No. 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74

2c

Bond C13-C14-H16 C9-C10-H15 C11-C10-H15 C9-C24-H25 C9-C24-H26 C27-C24-H25 C27-C24-H26 C24-C27-H28 C32-C27-H28 C37-C36-H42 C41-C36-H42 C39-C40-H43 C41-C40-H43 C44-C45-H50 C46-C45-H50 C44-C49-H51 C48-C49-H51 C44-C59-H60 C44-C59-H61 C62-C59-H60 C62-C59-H61 C59-C62-H63 C67-C62-H63 C1-C2-I19 C3-C2-I19 C3-C4-I18 C5-C4-I18 C10-C11-I21 C12-C11-I21 C12-C13-I20 C14-C13-I20 C36-C37-I54 C38-C37-I54 C38-C39-I53 C40-C39-I53 C45-C46-I56 C47-C46-I56

Angle 120.76 119.67 119.60 109.19 110.84 108.93 107.34 108.38 106.31 120.12 120.63 122.03 119.03 119.67 119.60 118.80 120.76 109.19 110.84 108.93 107.34 108.37 106.31 119.26 119.62 119.60 118.89 119.36 120.32 120.13 119.21 119.26 119.62 119.60 118.89 119.36 120.32

2c. Calculated bond angles of Thyroxine cyclic dimer

Sl. No. 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110

Bond C47-C48-I55 C49-C48-I55 C2-C3-O22 C4-C3-O22 C1-C6-O17 C5-C6-O17 C11-C12-O17 C13-C12-O17 C27-C32=O33 C27-C32-O34 C6-O17-C12 C37-C38-O57 C39-C38-O57 C36-C41-O52 C40-C41-O52 C46-C47-O52 C48-C47-O52 C62-C67=O68 C62-C67-O69 C41-O52-C47 C24-C27-N29 C32-C27-N29 C59-C62-N64 C67-C62-N64 C27-N29-H30 C27-N29-H31 C62-N64-H65 C62-N64-H66 O33=C32-O34 O68=C67-O69 C3-O22-H23 C32-O34-H35 C38-O57-H58 C67-O69-H70 O33-H70-O69 O34-H35-O68

Angle 120.13 119.21 117.86 124.06 123.66 115.23 120.41 120.40 122.29 114.47 120.64 117.86 124.06 123.66 115.23 120.41 120.40 122.29 114.48 120.64 111.46 113.37 111.46 113.51 113.94 115.24 113.94 115.24 123.21 123.21 112.43 114.74 112.43 114.74 173.13 173.13

ACCEPTED MANUSCRIPT

3Table

Parameters ELUMO EHOMO EHOMO- ELUMO Hardness(η)= 1/2(ELUMO- EHOMO) chemical potential(μ) 1/2(EHOMO+ELUMO) Global electrophilicity index(ω) μ2/2 η IE = -EHOMO EA=-ELUMO

3

Monomer Hartee eV -0.066 -1.796 -0.229 -6.231 0.163 4.435 0.081 2.204

Chain dimer Hartee eV -0.069 -1.877 -0.227 -6.177 0.158 4.299 0.079 2.150

Cyclic dimer Hartee eV -0.068 -1.850 -0.230 -6.258 0.162 4.408 0.081 2.204

-0.148

-4.027

-0.148

-4.027

-0.149

-4.054

0.134

3.646

0.139

3.782

0.137

3.728

0.229 0.066

6.231 1.796

0.227 0.069

6.177 1.877

0.230 0.068

6.258 1.850

3. Electrical properties of Thyroxine

4Table

4

Donor (i)

ED (i) (e)

Energy (i) (a.u)

Acceptor (j)

ED (j) (e)

Energy (j) (a.u)

E(2) (kJ/mol)

E(j)–E(i) (kcal/mol)

Fij (a.u)

σ(C1-C2) σ(C1-C2) σ(C1-C2) σ(C1-C2) σ(C1-C6) σ(C1-C6) σ(C2-C3) σ(C4-I18) σ(C6-O17) π(C9-C10) π(C9-C10) π(C11-C12) σ(C12-O17) σ(C27-N29) n1(C6) n1(O17) n2(O17) n2(I18) n1(N29) n2(O33) n2(O33) * π (C11-C12)

1.97462 1.97462 1.97462 1.97462 1.97017 1.97017 1.96478 1.96688 1.97777 1.64636 1.64636 1.69153 1.98535 1.98414 1.03167 1.93224 1.88344 1.95825 1.93186 1.85877 1.85877 0.42783

-0.73357 -0.73357 -0.73357 -0.73357 -0.72418 -0.72418 -0.73652 -0.51679 -0.86068 -0.26793 -0.26793 -0.29741 -0.88374 -0.74479 -0.14114 -0.54709 -0.33459 -0.28758 -0.28390 -0.29636 -0.29636 -0.01227

σ*(C1-C6) σ*(C2-C3) σ*(C6-O17) σ*(C3-O22) σ*(C1-C2) σ*(C2-I19) σ*(O22-H23) σ*(C2-C3) σ*(C1-C2) π*(C11-C12) π*(C13-C14) π*(C9-C10) σ*(C10-C11) σ*(C32-O33) π*(C1-C2) σ*(C1-C6) σ*(C11-C12) σ*(C4-C5) σ*(C27-C32) σ*(C27-C32) σ*(C32-O34) π*(C9-C10)

0.03203 0.04139 0.04165 0.02759 0.02051 0.03511 0.02566 0.04139 0.04139 0.42783 0.36194 0.33828 0.02293 0.02209 0.40495 0.03203 0.04700 0.02019 0.08118 0.08118 0.11031 0.33828 \

0.51595 0.49486 0.26682 0.27193 0.52198 0.03511 0.36881 0.49486 0.52198 -0.01227 0.00568 0.01557 0.50922 0.47879 0.00267 0.51595 0.49267 0.51392 0.32175 0.32175 0.23202 0.01557

2.44 2.19 5.46 3.53 2.79 4.37 2.70 6.47 2.41 23.35 22.69 19.20 2.38 1.61 78.03 6.80 7.22 2.53 10.52 15.85 34.32 113.86

1.25 1.23 1.00 1.01 1.25 0.75 1.11 1.01 1.38 0.26 0.27 0.31 1.39 1.22 0.14 1.06 0.53 0.80 0.61 0.62 0.53 0.03

0.049 0.046 0.066 0.053 0.053 0.051 0.049 0.072 0.052 0.070 0.070 0.070 0.052 0.040 0.112 0.077 0.061 0.040 0.071 0.090 0.121 0.081

Chain Dimer From Monomer2 n2(I53) 1.96228 n2(I54) 1.97164 n1(O57) 1.93960 n1(O57) 1.93960

-0.28033 -0.27614 -0.57209 -0.57209

σ*(C32-O33) σ*(C32-O34) σ*(C27-C32) σ*(C32-O34)

0.02699 0.08679 0.07660 0.08679

Monomer1 0.45368 0.27750 0.33094 0.27750

0.07 0.08 0.17 0.13

0.73 0.55 0.90 0.85

0.006 0.006 0.011 0.009

Monomer1 0.31793 0.30020 0.41870 0.06910

0.06 0.09 0.06 0.07

0.75 0.73 0.99 0.28

0.006 0.007 0.007 0.004

Cyclic Dimer From Monomer2 n2(O68) 1.84734 n2(O68) 1.84734 n1(O69) 1.96714 n2(O69) 1.75171

-0.42913 -0.42913 -0.56821 -0.35218

σ*(C27-C32) σ*(C32-O34) σ*(C32-O33) π*(C32-O33)

0.07543 0.07263 0.03500 0.28363

4. Second Order perturbation theory analysis of Fock matrix in NBO basis for Thyroxine

E(2) means energy of hyper conjugative interaction (stabilization energy). E(j)–E(i) is the energy difference between donor and acceptor i and j NBO orbitals. F(i, j) is the Fork matrix element between i and j NBO orbitals.

5Table

Monomer Atom with Mulliken IUPAC atomic Numbering charges C1 -0.247 C2 -0.452 C3 0.578 C4 -0.465 C5 -0.347 C6 0.393 H7 0.272 H8 0.276 C9 0.530 C10 -0.413 C11 -0.467 C12 0.561 C13 -0.478 C14 -0.313 H15 0.253 H16 0.297 O17 -0.334 I18 0.127 I19 0.145 I20 0.138 I21 0.144 O22 -0.438 H23 0.356 C24 -0.526 H25 0.204 H26 0.221 C27 -0.120 H28 0.252

Atom with IUPAC Numbering C1 C2 C3 C4 C5 C6 H7 H8 C9 C10 C11 C12 C13 C14 H15 H16 O17 I18 I19 I20 I21 O22 H23 C24 H25 H26 C27 H28

Chain dimer Mulliken Atom with atomic IUPAC charges Numbering -0.248 C36 -0.451 C37 0.578 C38 -0.464 C39 -0.347 C40 0.394 C41 0.272 H42 0.276 H43 0.530 C44 -0.398 C45 -0.469 C46 0.557 C47 -0.479 C48 -0.306 C49 0.255 H50 0.286 H51 -0.335 O52 0.125 I53 0.145 I54 0.136 I55 0.141 I56 -0.438 O57 0.356 H58 -0.539 C59 0.207 H60 0.220 H61 -0.129 C62 0.251 H63

5

Mulliken atomic charges -0.248 -0.481 0.690 -0.496 -0.336 0.395 0.273 0.277 0.519 -0.400 -0.470 0.558 -0.480 -0.305 0.256 0.292 -0.333 0.155 0.128 0.140 0.143 -0.583 0.423 -0.529 0.221 0.212 -0.118 0.250

Atom with IUPAC Numbering C1 C2 C3 C4 C5 C6 H7 H8 C9 C10 C11 C12 C13 C14 H15 H16 O17 I18 I19 I20 I21 O22 H23 C24 H25 H26 C27 H28

Cyclic dimer Mullike Atom with n atomic IUPAC charges Numbering -0.198 C36 -0.504 C37 0.603 C38 -0.561 C39 -0.310 C40 0.375 C41 0.267 H42 0.265 H43 0.595 C44 -0.363 C45 -0.528 C46 0.586 C47 -0.544 C48 -0.271 C49 0.249 H50 0.244 H51 -0.316 O52 0.162 I53 0.163 I54 0.163 I55 0.163 I56 -0.426 O57 0.347 H58 -0.602 C59 0.233 H60 0.207 H61 -0.135 C62 0.247 H63

Mulliken atomic charges -0.198 -0.504 0.603 -0.561 -0.310 0.375 0.267 0.265 0.595 -0.363 -0.528 0.586 -0.544 -0.271 0.249 0.244 -0.316 0.162 0.163 0.163 0.163 -0.426 0.347 -0.602 0.233 0.207 -0.135 0.247

N29 H30 H31 C32 O33 O34 H35

-0.607 0.293 0.289 0.195 -0.247 -0.464 0.394

N29 H30 H31 C32 O33 O34 H35

-0.607 0.297 0.286 0.231 -0.327 -0.465 0.450

N64 H65 H66 C67 O68 O69 H70

-0.608 0.294 0.288 0.190 -0.257 -0.449 0.392

N29 H30 H31 C32 O33 O34 H35

5. Mullikan’s atomic charges for optimized geometry of Thyroxine

-0.529 0.259 0.292 0.205 -0.323 -0.442 0.428

N64 H65 H66 C67 O68 O69 H70

-0.529 0.259 0.292 0.205 -0.323 -0.442 0.428

ACCEPTED MANUSCRIPT

6Table

Parameters SCF energy (Hartee) Total energy (thermal), Etotal (kCal mol-1) Zero –point vibrational energy (kCal mol-1) Rotational temperature (Kelvin)

6

Monomer -979.228 163.143

Chain dimer -1958.479 328.306

Cyclic dimer -1958.493 328.120

147.271

295.481

295.712

0.005 0.002 0.002 0.001 0.002 0.001 A 0.100 A 0.041 A Rotational constants (GHz) B 0.038 B 0.004 B C 0.038 C 0.004 C μx -3.306 μx -7.103 μx Dipole moment (Debye) μy -1.442 μy 1.202 μy μz 0.757 μz 0.900 μz μTotal 3.685 μTotal 7.260 μTotal Binding Energy of Thyroxine chain dimer = -14.433kcal mol-1 Binding Energy of Thyroxine cyclic dimer = -23.218 kcal mol-1 6. The Thermo dynamical parameter of Thyroxine

0.002 0.001 0.001 0.046 0.003 0.003 0.001 0.004 -1.261 1.261

7aTable

Mode

DFT

Raman

FTIR

(Wavenumber)

(Expt.)

(Expt.)

7a

Vibrational Assignments

1

3531.68

υas(N29H2)100

2

3509.57

υ(O34-H)100

3

3496.12

4

3409.63

5

3127.09

6

3126.13

υ(C14-H) (ring1)99

7

3118.44

υ(C1-H) (ring1)99

8

3096.34

υ(C10-H) (ring2)99

9

3013.70

10

2992.55

11

2942.58

2934

2887

υs(C24H2)99

12

1644.27

1600

1630

υ(C32=O)82

13

1621.21

β(N29H2)84, τ(H30-N29-C27-C24), τ(H31-N29-C27-C24)13

14

1571.24

υ(C=C) (ring1)56

15

1553.94

υ(C=C) (ring2)45

16

1538.56

υ(C=C) (ring1)49

17

1516.46

3471

υ(O22-H)100 υs(N29H2)99 υ(C5-H) (ring1)99

3154

3050

υ(C27-H)88, υas(C24H2)12 υ(C27-H)12, υas(C24H2)88

1498

υ(C=C) (ring2)54

1440

β(C24H2)84

18

1456.88

19

1423.24

υ(C=C) (ring1)19

20

1402.10

υ(C=C) (ring2)19

21

1370.39

υ(C=C) (ring2)15

22

1367.50

υ(C=C) (ring1), υ(C3-O)29

23

1353.09

β(H30-N29-C27)14, β(H28-C27-N29)28

24

1319.45

υ(C12-O)25

25

1313.69

26

1295.43

υ(C=C) (ring2)31, β(H35-O34-C32)11

27

1278.13

υ(C=C) (ring2)53

28

1254.10

29

1242.57

β(H30-N29-C27)21, β(N29-C27-C24)13

30

1237.77

β(H35-O34-C32)14

31

1221.43

32

1200.29

υ(C3-O)10, υ(C9-C24)12, β(H8-C5-C6)17

33

1193.56

β(H15-C10-C11)47

34

1183.95

35

1152.24

1162

36

1116.68

1120

37

1112.84

β(H23-O22-C3)45

38

1086.89

υ(C27-N), υ(C24-C27)67

39

1056.14

1316

1309

υ(C3-O)39, β(H7-C1-C2)20

1248

1230

1054

υ(C=C) (ring1)50, β(H23-O22-C3)23, υ(C3-O22)10

υ(C12-O)21, υ(C6-O)10, β(H7-C1-C2)14

1180

υ(C9-C24)11, β(H16-C14-C13)45

1143

υ(C6-O)26, β(H7-C1-C2)15, β(H8-C5-C6)14 β(H30-N29-C27)26, β(H25-C24-C9)22

β(H35-O34-C32)39

40

1023.46

β(C10- C11-C12), β(C11- C12-C13), β(C12- C13-C14)57

41

1013.86

β(H8-C5-C6)13, β(C2- C1-C6), β(C4- C5-C6)42

42

959.08

970

43

913.91

916

44

899.50

τ(H15-C10-C11-C12)48

45

885.08

τ(H7-C1-C2-C3)25, τ(H8-C5-C6-C1)63

46

881.24

υ(C6-O)11, τ(H7-C1-C2-C3)53, τ(H8-C5-C6- C1)84

47

878.35

γ(C1-C5-O17-C6)13, τ(H7-C1-C2-C3)53, τ(H8-C5-C6-C1)71

48

865.86

υ(C27-N), υ(C24-C27)42, τ(H25-C24-C9-C10)23, τ(H26-C24-C9-C10), τ(H28-

979

υ(C27-N), υ(C24-C27)17, β(H30-N29-C27)20, τ(H7-C1-C2-C3)10 τ(H15-C10-C11-C12)12, τ(H16-C14-C13-C12)68

C27-C32- O34)25, τ(H25-C24-C9-C10)16 49

853.37

50

811.08

51

788.02

52

755.35

854

υ(C9-C24)11, β(C11- C12-C13), β(C12- C13-C14)15 β(C2- C1-C6)25

806 781

υ(C3-O)10, υ(C32-C27)10, β(C2- C1-C6), β(C4- C5-C6)10, β(C5-C6-O17)13 β(C6- O17-C12)14, τ(C9-C10-C11-C12), τ(C10-C11-C12-C13), τ(C11-C12-C13-

770

C14), γ(I20- C12-C14-C13), γ(I21-C10-C12-C11)39 53

717.87

54

716.91

β(N29-C27-C32)10, τ(O33-C27-O34-C32) 37 707

τ(C2-C1-C6-C5), τ(C3-C2-C1-C6), τ(C4-C5-C6- C17), γ(O22-C2-C4-C3), γ(I18-C3-O5-C4)66 τ(O33-C27-O34-C32) 13

55

695.76

56

680.39

57

670.78

υ(C4-I), υ(C2-I)12, β(C1- C2-C3)10, β(C2- C1-C6), β(C4- C5-C6)38

58

640.03

τ(H30-N29-C27-C24), τ(H31-N29-C27-C24)59

676

υ(C13-I)13, υ(C11-I)14, β(C10- C11-C12)14, β(C12- C13-C14)45

59

607.35

γ(C24-C10-C14-C9)18

60

596.78

β(O33=C32-O34), β(C1-C6-O17)18 , γ(C32-C24-N29-C27)10

61

567.95

τ(H35-O34-C32-C27), γ(C1-C5-O17-C6), τ(C9-C10-C11-C12), τ(C10-C11-C12C13), τ(C11- C12-C13-C14), γ(O17-C11-C13-C12), γ(I20-C12-C14-C13), γ(I21C10-C12-C11)76

62

567.95

63

551.61

γ(C1-C5-O17-C6)42 557

β(O34- C32-C27)13, β(C1- C2-I19), β(C2- C3-O22), β(C5- C4-I18), β(C10C11-I12)16, τ(H35-O34-C32-C27)82

64

β(O33=C32-O34), β(C1-C6-O17)10, β(O17- C12-C13)20, β(C10- C11-I12),

514.14

β(C14- C13- I20)13 β(O33=C32-O34), β(C1-C6-O17)16, β(O17- C12-C13)23

65

503.56

504

66

494.92

τ(C9-C10-C11-C12), γ(I20-C12-C14-C13)46

67

492.03

β(C1- C2-I19), β(C2- C3-O22), β(C5- C4-I18), β(C10- C11-I12)21, τ(C9-C10C11-C12), γ(I20-C12-C14-C13)11 τ(C2-C1-C6-C5), τ(C4-C5-C6-O17), γ(I18-C5- C3-C4)67

68

485.30

69

467.05

70

376.71

71

356.53

τ(H23-O22-C3-C4), τ(C3-C2-C1-C6), γ(O22-C4-C2-C3)34

72

351.73

τ(H23-O22-C3-C4), τ(C3-C2-C1-C6), γ(O22-C4-C2-C3)40

73

348.84

τ(H23-O22-C3-C4), τ(C3-C2-C1-C6), γ(O22-C2-C4-C3)58

74

330.58

β(C1- C2-I19), β(C2- C3-O22), β(C5- C4-I18), β(C10- C11-I12)10

438 411

334

β(C24- C9-C14)13, β(N29-C27-C24)11

β(C10- C11-C12)14, β(C12- C13-C14)10, τ(H30-N29-C27-C24), τ(H31-N29C27-C24)13

75

323.86

76

275.81

β(N29-C27-C24)10, τ(H31-N29-C27-C24)14 270

β(O34- C32-C27)12, β(N29-C27-C24)12, τ(H30-N29-C27-C24), τ(H31-N29C27-C24)48

77

256.59

β(O34- C32-C27)17, τ(H30-N29-C27-C24), τ(H31-N29-C27-C24)26

78

246.98

β(O34- C32-C27)10, β(N29-C27-C32)13

79

236.41

β(O22- C3-C2), β(I19- C2-C1), β(I18- C4-C5), β(I20- C14-C13)45

80

228.72

β(O17- C12-C13)18, β(C10- C11-I12), β(C14- C13-I20)12, τ(C2-C1-C6-C5), τ(C4-C5-C6-O17)11

81

207.58

β(C1- C2-I19), β(C5- C4-I18), β(C10- C11-I12), β(C14- C13-I20)11

82

178.75

τ(C14-C13-C12-C11), γ(I20-C12-C14-C13), γ(I21-C10-C12-C11)11

83

175.86

τ(C2-C1-C6-C5), τ(C3-C2-C1-C6), τ(C4-C5-C6-C17), γ(O22-C2-C4-C3), γ(I18-C3-O5- C4)76 τ(C9-C10-C11-C12)15, τ(C11-C12-C13-C14), γ(I21-C10-C12-C11)66

84

168.18

85

159.53

86

143.19

β(N29-C27-C32)16, γ(C32-C24-N29-C27)12,

87

119.16

β(C10- C11-I12), β(C14- C13-I20)13, τ(C2-C1-C6-C5), τ(C4-C5-C6-O17)52

88

110.52

β(O22- C3-C2), β(I19- C2-C1), β(I18- C4-C5), β(I20- C14-C13)11

89

97.06

β(C1- C2-I19), β(C5- C4-I18), β(C10- C11-I12), β(C14- C13-I20)57

90

72.08

τ(C2-C1-C6-C5)25, τ(C3-C2-C1-C6), γ(I19-C1-C3-C2), γ(I18-C5-C3-C4),

156

β(C24- C9-C14)14, β(C10- C11-I12), β(C14- C13-I20)16

γ(I22-C2-C4- C3)62 91

69.19

β(C5- C4-I18), β(C10- C11-I12), β(C14- C13-I20)68

92

61.50

β(C27- C24-C9), β(C24- C9-C14)24, τ(C14-C13-C12-C11), γ(I20-C12-C14-C13),

γ(I21-C10- C12-C11)11, γ(C24-C10-C14-C9)24 93

40.36

β(C6- O17-C12)16, τ(C14-C13-C12-C11), γ(I20-C12-C14-C13), γ(I21-C10-C12C11)41

94

39.40

γ(C9-C24-C27-N29), γ(C24-C27-C32-O34)50

95

33.64

γ(C9-C24-C27-N29), γ(C24-C27-C32-O34)75

96

15.38

β(C6- O17-C12)15, τ(C27-C24-C9-C10)13, τ(C10-C11-C12-C13), γ(O17-C11C13-C12)39

97

13.45

τ(C6-O17-C12-C11)60, τ(C27-C24-C9-C10)45

98

10.57

τ(C6-O17-C12-C11)17

99

7.69

τ(C5-C6-O17-C12)77 7a. The experimental and theoretical peak frequencies of vibrational frequencies assigned for Thyroxine monomer

υ-stretching, υ - symmetric stretching, υ - asymmetric stretching, τ- torsion, β- in plane bending, γ- out of plane bending s as

7bTable

Mode

DFT

Raman FTIR

(Wavenumber)

(Expt.) (Expt.)

7b

Vibrational Assignments

1

3530.71

υas(N29H2)99

2

3526.87

υas(N64H2)98

3

3499.00

υ(O69-H)100

4

3495.16

υ(O22-H)100

5

3410.59

υs(N29H2)99

6

3406.74

υs(N64H2)98

7

3246.26

8

3157.85

9

3130.94

υ(C14-H) (ring2)99

10

3127.71

υ(C49-H) (ring4)98

11

3127.64

υ(C40-H) (ring3)98

12

3126.13

υ(C5-H) (ring1)99

13

3121.33

υ(C36-H) (ring3)99

14

3118.44

υ(C1-H) (ring1)99

15

3096.34

υ(C45-H) (ring4)99

16

3095.38

υ(C10-H) (ring2)99

17

3013.70

18

3011.77

υas(C59H2)82, υ(C62-H)14

19

2995.44

υas(C24H2)81, υ(C27-H)19

3235

υ(O57-H)93 υ(O34-H)89

3154

3050

υas(C24H2)19, υ(C27-H)80

20

2993.52

υas(C59H2)11, υ(C62-H)85

21

2945.75

υs(C59H2)93

22

2945.13

23

1642.35

24

1631.78

25

1624.09

26

1603.91

27

1571.14

υ(C=C) (ring3)56

28

1570.89

υ(C=C) (ring1)57

29

1553.80

υ(C=C) (ring2)53

30

1553.55

υ(C=C) (ring4)56

31

1538.56

υ(C=C) (ring1)55

32

1534.72

υ(C=C) (ring3)55

33

1517.38

υ(C=C) (ring4)56

34

1517.03

35

1460.72

36

1458.80

37

1423.24

υ(C=C) (ring1)31

38

1422.28

υ(C=C) (ring3)34

39

1402.10

υ(C=C) (ring2)55

40

1401.14

υ(C=C) (ring4)60

41

1372.31

υ(C32-O34)13, β(H35-O34-C32), β(O34-H35-O57), β(H35-O57-C38)26, β(H28-C27-N29)13

2934

2887

υs(C24H2)99 υ(C67=O)73

1630

υ(C67=O)11, β(N64H2)72, τ(H65-N64-C62-C59)29, τ(H66-N64-C62-C59)11 β(N29H2)82,τ(H30-N29-C27-C24),τ(H31-N29-C27-C24)14 υ(C32=O)66

1600

1498

υ(C=C) (ring2)75 β(C59H2)80 1440

β(C24H2)82

42

1369.42

β(H63-C62-N64)27

43

1368.46

β(H28-C27-N29)25

44

1366.54

υ(C=C) (ring1)18

45

1365.58

υ(C=C) (ring3), υ(C38-O57)22

46

1364.62

β(H63-C62-N64)28

47

1351.17

β(H30-N29-C27)13, β(H28-C27-N29)46

48

1313.69

υ(C=C) (ring1), υ(C3-O22)21, β(H23-O22-C3)10

49

1312.73

50

1307.92

β(C59H2)10

51

1299.27

υ(C=C) (ring3)69

52

1289.66

υ(C=C) (ring4)37

53

1284.86

υ(C=C) (ring2)60, β(H25-C24-C9)10,

54

1274.29

υ(C=C) (ring4)21, υ(C62-C67), υ(C67-O69)13, β(H70-O69-C67)18

55

1255.07

υ(C3-O22)15

56

1253.14

57

1246.42

β(H65-N64-C62)21

58

1245.46

υ(C38-O57)52, β(H42-C36-C41)11

59

1240.65

β(H30-N29-C27)24, γ(N29-C24-C32-C27)11

60

1221.43

61

1219.51

υ(C47-O52)15, β(H58-O57-H35)12, β(H42-C36-C41)16

62

1214.70

β(H70-O69-C67)17, β(N64-C62-C59)10

63

1201.25

υ(C44-C59)15, β(H43-C40-C41)12

1316

1309

υ(C=C) (ring1), υ(C3-O22)22, β(H23-O22-C3)10

υ(C3-O22)65, β(H7-C1-C6), β(H8-C5-C6)12

1248

1230

υ(C6-O17), υ(C12-O17)45, β(H8-C5-C6)13

64

1200.29

υ(C3-O22)16, υ(C6-O17), υ(C12-O17)10, υ(C9-C24)13, β(H8-C5-C6)17

65

1194.52

β(H50-C45-C46)41

66

1193.56

β(H15-C10-C9)36

67

1186.84

β(H16-C14-C9)37

68

1184.91

69

1178.19

70

1151.86

71

1151.79

72

1114.76

73

1111.88

β(H23-O22-C3)48

74

1106.55

υ(C62-N64)22, β(H30-N29-C27)11, β(H25-C24-C9)13

75

1106.16

υ(C62-N64)25, β(H30-N29-C27)10, β(H25-C24-C9)12

76

1091.70

υ(C27-N29)33, β(H58-O57-H35)13

77

1088.81

υ(C27-N29)23, υ(C24-C27)12, β(H58-O57-H35)13

78

1041.72

79

1023.62

β(C9-C10-C11), β(C9-C14-C13), β(C10-C9-C14)45

80

1023.47

υ(C47-O52)10, β(C44-C45-C46), β(C44-C49-C48), β(C45-C44-C49)46

81

1014.82

β(H43-C40-C41)11, β(C41-C36-C37), β(C39-C40-C41)45

82

1012.89

β(H7-C1-C6), β(H8-C5-C6)16, β(C1-C6-C5), β(C2-C1-C6), β(C4-C5-C6)43

83

967.73

84

961.00

85

911.99

1180

υ(C44-C59)10, β(H51-C49-C48)47 υ(C32-O34)18, υ(C27-C32)12 υ(C6-O17), υ(C12-O17)21, υ(C41-O52)10, β(H7-C1-C6), β(H8-C5-C6)12

1162 1143

β(H65-N64-C62)28, β(H60-C59-C44)31

1120

υ(C62-C67), υ(C67-O69)44, β(H70-O69-C67)36

1054

970

υ(C6-O17), υ(C12-O17)12, υ(C41-O52)17, β(H43-C40-C41)13

979

υ(C62-C59)20, υ(C27-N)12, τ(H60-C59-C44-C45), τ(H61-C59-C44-C45)18 υ(C24-C27)12, β(H30-N29-C27)15

916

τ(H51-C49-C48-C47)47

86

908.14

τ(H50-C45-C46-C47)58, τ(H51-C49-C48-C47)14

87

907.18

τ(H15-C10-C9-C24)49, τ(C11-C10-C9-C14), τ(C10-C9-C14-C13), γ(I20-C12-C14-C13)11

88

905.26

τ(H15-C10-C9-C24), τ(H16-C14-C9-C24)90

89

888.92

τ(H7-C1-C6-C5)76, τ(H8-C5-C6-C1)12

90

884.12

τ(H42-C36-C41-C40)12, τ(H43-C40-C41-C36)72

91

883.16

β(C45-C44-C49)10

92

882.20

β(C10-C9-C14)15

93

878.35

τ(H8-C5-C6-C1)66, γ(C1-C5-O17-C6), τ(C1-C6-C5-C4), τ(C3-C2-C1-C6), γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)12

94

877.39

τ(H35-O34-C32-C27), τ(C32-O34-H35-O57)84

95

872.59

τ(H42-C36-C41-C40)62, γ(C40-C36-O52-C41), τ(C36-C37-C38-O57), τ(C39-C40-C41-C36), γ(I54C36-C38-C37)24, γ(I53-C38-C40-C39)14

96

868.74

υ(C62-N64)10, υ(C62-C59)12, τ(H60-C59-C44-C45), τ(H61-C59-C44-C45)18

97

863.94

υ(C27-N29)13, υ(C24-C27)20, τ(H25-C24-C9-C10), τ(H28-C27-C32-O33)15

98

854.33

99

853.37

β(C2- C1-C6), β(C4- C5-C6)25

100

831.26

υ(C62-C67)19

101

828.38

υ(C27-C32)18

102

789.94

103

788.02

104

755.35

105

753.42

854

β(C1-C6-C5), β(C4-C5-C6), β(C36-C41-C40), β(C37-C36-C41),25

806 781 770

υ(C32-C27)10, β(C2- C1-C6), β(C4- C5-C6)15

β(C1-C6-C5)14 β(C47-O52-C41)16, τ(C44-C45-C46-C47)36 β(C6-O17-C12)14, γ(O17-C11-C13-C12), τ(C9-C10-C11-C12)40

106

717.03

τ(C3-C2-C1-C6), γ(O22-C2-C4-C3), γ(I18-C3-C5-C4)82

107

716.75

τ(C41-C36-C37-C38)46, γ(I54-C36-C38-C37), γ(I53-C38-C40-C39), τ(C39-C40-C41-C36), τ(C36C37-C38-O57), γ(C40-C36-O52-C41)20 β(C3-C2-C1)10, γ(O33-C27-O34-C32)14

108

711.14

109

707.30

110

692.88

γ(O33-C27-O34-C32)20

111

689.04

β(C37-C36-C41)15, γ(O68-C62-O69-C67)26

112

680.41

υ(C46-I56)11, υ(C48-I55)10, β(C44-C45-C46), β(C44-C49-C48)49

113

680.21

υ(C11-I21)12, υ(C13-I20)11, β(C9-C14-C13), β(C12-C11-C10)51

114

674.62

115

671.74

υ(C39-I53), υ(C37-I54)13, β(C37-C36-C41)24, γ(O68-C62-O69-C67)14

116

665.97

τ(H65-N64-C62-C59)29, τ(H66-N64-C62-C59)57

117

657.32

τ(H30-N29-C27-C24),τ(H31-N29-C27-C24)31, τ(H58-O57-H35-O34), τ(C32-O34-H35-O57)14

118

651.56

τ(H58-O57-H35-O34), τ(C32-O34-H35-O57)72

119

623.69

β(O33=C32-O34)19, τ(H30-N29-C27-C24),τ(H31-N29-C27-C24)26

120

616.00

υ(C62-C67)10, β(O68=C67-O69)27

121

603.51

τ(H70-O69-C67-C62)19

122

601.59

τ(H70-O69-C67-C62)10, γ(C24-C10-C14-C9)14

123

572.76

β(C37-C38-O57)18, τ(H70-O69-C67-C62)10

124

569.29

β(C62-C67-O69), β(C67-C62-N64)10, τ(H70-O69-C67-C62)39

125

569.24

γ(C1-C5-O17-C6), τ(C3-C2-C1-C6), γ(O22-C2-C4-C3)51

126

565.07

γ(C40-C36-O52-C41), τ(C36-C37-C38-O57), τ(C39-C40-C41-C36), γ(I54-C36-C38-C37), γ(I53-C38-

707

676

β(C45-C44-C49)10, γ(O68-C62-O69-C67)10

υ(C2-I19)14, υ(C4-I18)10, β(C1-C2-C6), β(C4-C5-C6)26

C40-C39)46 β(C5-C6-O17)11

127

559.30

128

522.78

β(C37-C38-O57)24

129

515.10

β(O33=C32-O34)16

130

507.88

β(C46-C47-O52), β(I56-C46-C45)73

131

507.19

132

496.84

β(C4-C3-O22)38

133

493.95

τ(C45-C44-C49-C48), τ(C46-C45-C44-C49),γ(I55-C47-C49-C48), γ(I56-C45-C47-C46)76

134

492.99

β(C4-C3-O22), τ(C11-C10-C9-C14), τ(C10-C9-C14-C13), γ(I20-C12-C14-C13)44, τ(C9-C10-C11-

557

β(O17-C12-C13), β(I20-C13-C14), β(I21-C11-C10)63

504

C12)12 135

487.23

τ(C37-C36-C41-O52), γ(I53-C38-C40-C39)67

136

486.27

τ(C2-C1-C6-C5), τ(C4-C5-C6-C1), γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)84

137

483.38

γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)44

138

469.93

γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)28

139

467.05

140

385.36

141

384.40

β(C13-C12-O17), β(C24-C27-N29)33

142

364.22

τ(C36-C37-C38-O57)29, τ(O52-C41-C36-C37)10

143

357.49

τ(C2-C1-C6-C5), γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(O22-C2-C4-C3)22, γ(C1-C5-O17-C6)47

144

355.57

γ(C36-C37-O38-C57), γ(C37-C36-O41-C52)55

145

350.76

β(C5-C6-O17)10, τ(C2-C1-C6-C5), γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(O22-C2-C4-C3)22,

β(O68=C67-O69)14, β(N64-C62-C59)13, β(C62-C67-O69), β(C67-C62-N64)23

438 411

β(N64-C62-C59)13, β(C62-C67-O69), β(C67-C62-N64)10

γ(C1-C5-O17-C6)21

τ(H23-O22-C3-C2)85

146

345.96

147

337.31

148

331.54

β(C13-C12-O17), β(C24-C27-N29)19

149

329.62

τ(H30-N29-C27-C24), τ(H31-N29- C27-C24)13

150

328.66

β(C13-C12-O17), β(C24-C27-N29)15

151

305.60

υ(O57-H35)11, β(O34-C32-C27)13, γ(N29-C24-C32-C27)16

152

274.85

153

266.20

β(O34-C32-C27)13

154

249.86

τ(H30-N29-C27-C24),τ(H31-N29-C27-C24)10

155

248.90

τ(H30-N29-C27-C24),τ(H31-N29-C27-C24)57

156

247.94

β(O34- C32-C27)10, β(N29-C27-C32)18

157

236.41

β(C4-C3-O22), β(I19-C2-C1)14, , β(I18-C4-C5)35

158

231.60

β(C45-C46-I56), β(C46-C47-O52), β(C49-C48-I55)31, τ(C36-C37-C38-O57), τ(C37-C36-C41-O52)11

159

228.72

β(C13-C12-O17), β(C24-C27-N29)14, τ(C2-C1-C6-C5), γ(I18-C3-C5-C4)11

160

219.11

β(C1- C2-I19), β(C5- C4-I18), β(C10- C11-I12), β(C14- C13-I20)15

161

209.50

β(C14-C13-I20), β(C13-C12-O17), β(C10-C11-I21)12

162

194.12

τ(H65-N64-C62-C59)29, τ(H66-N64-C62-C59)77

163

185.47

τ(C14-C13-C12-C11), γ(I20-C12-C14-C13), γ(I21-C10-C12-C11)28

164

184.51

τ(C39-C40-C41-C36)15, τ(O52-C41-C36-C37)13

165

177.10

τ(C1-C6-C5-C4), τ(C2-C1-C6-C5), γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)85

166

177.05

τ(C36-C41-C40-C39), τ(C37-C36-C41-O52),

334

270

β(C24-C27-N29), β(C59-C62-N64)21

β(O69-C67-C62)35, β(C67-C62-N64)41, γ(C67-C59-N64-C62)10

γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)60

167

τ(C45-C44-C49-C48), τ(C46-C45-C44-C49)

172.02

γ(I55-C47-C49-C48), γ(I56-C45-C47-C46)76 168

171.06

τ(C45-C44-C49-C48), τ(C46-C45-C44-C49)50, γ(I20-C12-C14-C13)24, γ(I21-C10-C12-C11)47,

169

166.25

γ(I20-C12-C14-C13)24, γ(I21-C10-C12-C11)25

170

165.29

β(I56-C46-C45)11

171

159.53

172

142.23

β(O69-C67-C62)35, β(C67-C62-N64)12, β(I56-C46-C45)18

173

125.89

β(C45-C46-I56), β(C46-C47-O52), β(C49-C48-I55)14, τ(C36-C37-C38-O57), τ(C37-C36-C41-O52)26

174

122.05

β(H35-O34-C32), β(H35-O57-C38), β(O34-H35-O57)11

175

119.16

τ(C2-C1-C6-C5), γ(I18-C3-C5-C4)34

176

113.40

β(I19-C2-C1)14, β(I18-C4-C5)10

177

110.52

υ(O57-H35)13, β(I54-C37-C36)22

178

99.94

β(C45-C46-I56), β(C40-C39-I53), β(C49-C48-I55)50

179

98.98

β(I19-C2-C1), β(I18-C4-C5), β(I21-C11-C10), β(I53-C39-C40), β(I56-C46-C45), β(I55-C48-C49)52

180

90.33

τ(H35-O34-C32-C27), τ(C32-O34-H35-O57)10, γ(I54-C36-C38-C37), γ(I53-C38-C40-C39), τ(C39-

156

β(I20-C13-C14), β(I21-C11-C10)33

C40-C41-C36), τ(C36-C37-C38-O57), γ(C40-C36-O52-C41)23 181

73.04

γ(I54-C36-C38-C37), γ(I53-C38-C40-C39), τ(C39-C40-C41-C36), τ(C36-C37-C38-O57), γ(C40-C36O52-C41)21

182

72.08

γ(C1-C5-O17-C6), τ(C1-C6-C5-C4), τ(C3-C2-C1-C6), γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)68

183

69.19

β(C45-C46-I56), β(C40-C39-I53), β(C49-C48-I55)63

184

68.23

β(C5-C6-O17), β(I20-C13-C14), β(I21-C11-C10), β(I18-C4-C5)73

185

61.50

β(C62-C59-C44)22, γ(C59-C45-C49-C44)28

186

46.13

τ(O69-C67-C62-C59)58

187

44.21

β(I54-C37-C36)11, γ(I56-C45-C47-C46)22

188

42.28

τ(O34-C32-C27-C24)50

189

40.36

τ(C11-C10-C9-C14), τ(C10-C9-C14-C13), γ(I20-C12-C14-C13)24, γ(I21-C10-C12-C11)52

190

34.60

β(I56-C46-C45)14, τ(N64-C62-C59-C44), τ(N64-C62-C59-C44), τ(C45-C44-C59-C62)49

191

33.64

β(C6-O17-C12)10, τ(H35-O34-C32-C27), τ(C32-O34-H35-O57)12

192

31.71

β(H35-O57-C38)26, τ(C32-C27-C24-C9)16

193

25.95

υ(O57-H35)10, β(H35-O57-C38)10, τ(H35-O57-C38-C37), τ(C27-C24-C9-C10), τ(C24-C27-C32C34)10

194

19.22

τ(C45-C44-C59-C62), τ(N64-C62-C59-C44)64

195

18.26

τ(H35-O57-C38-C37), τ(C27-C24-C9-C10), τ(C24-C27-C32-C34)21

196

14.42

τ(C45-C46-C47-O52)12, τ(C46-C47-O52-C41)29

197

13.45

τ(C45-C46-C47-O52)13, τ(C46-C47-O52-C41)27, τ(C6-O17-C12-C11)25

198

11.53

τ(C6-O17-C12-C11)40

199

9.61

τ(C47-O52-C41-C36)33

200

8.65

τ(C5-C6-O17-C12)77

201

7.69

τ(H35-O34-C32-C27), τ(C32-O34-H35-O57)11, τ(C47-O52-C41-C36)36

202

4.80

β(H35-O57-C38)19, τ(C32-C27-C24-C9)37

203

2.88

τ(C38-O57-H35-O34)10, τ(H35-O57-C38-C37), τ(C10-C9-C24-C27), τ(O34-C32-C27-C24)63

204

1.92

τ(C38-O57-H35-O34)50 7b. The experimental and theoretical peak frequencies assigned for Thyroxine chain dimer υ-stretching, υ - symmetric stretching, υ - asymmetric stretching, τ- torsion, β- in plane bending, γ- out of plane bending s as

M2cTable

Mode

DFT

Raman

FTIR

(Wavenumber)

(Expt.)

(Expt.)

2c

Vibrational Assignments

1

3531.51

υas(N64H2)99

2

3531.44

υas(N29H2)99

3

3495.43

υ(O22-H), υ(O57-H)100 In-phase

4

3495.41

5

3411.15

υs(N64H2)99

6

3411.08

υs(N29H2)99

7

3127.63

8

3127.61

υ(C-H) (ring1), υ(C-H) (ring3)94 Out of phase

9

3127.57

υ(C-H) (ring4)88

10

3127.56

υ(C-H) (ring2)93

11

3121.31

υ(C-H) (ring3)97

12

3121.30

υ(C-H) (ring1)97

13

3094.64

υ(C-H) (ring2)90

14

3094.63

υ(C-H) (ring4)90

15

3012.59

υ(C27-H), υ(C62-H)82 Out of phase, υas(C59H2)10

16

3012.50

17

2994.57

υ(C27-H), υ(C62-H)11 In-phase, υas(C59H2)80

18

2994.54

υ(C27-H), υ(C62-H)11 Out of phase, υas(C24H2)81

19

2943.33

υs(C24H2), υs(C59H2)95 In-phase

3471

3154

υ(O22-H), υ(O57-H)100 Out of phase

υ(C-H) (ring1), υ(C-H) (ring3)84 In-phase

3050

υ(C27-H), υ(C62-H)82 In-phase, υas(C24H2)10

2934

2887

υs(C24H2), υs(C59H2)95 Out of phase

20

2943.25

21

2695.31

υ(O34-H), υ(O69-H)98 Out of phase

22

2527.15

υ(O34-H), υ(O69-H)85 Out of phase

23

1625.28

1630

β(N29H2), β(N64H2)83 Out of phase, τ(H30-N29-C27-C24), τ(H31-N29-C27C24), τ(H65-C64-C62-C59), τ(H66-C64-C62-C59)14

24

β(N29H2), β(N64H2)83 In-phase, τ(H30-N29-C27-C24), τ(H31-N29-C27-C24),

1625.21

τ(H65-C64-C62-C59), τ(H66-C64-C62-C59)14 υ(C27-C32), υ(C32=O), υ(C67=O)46 In- phase

25

1586.64

1600

26

1575.77

υ(C32=O), υ(C67=O)72 Out of phase

27

1571.09

υ(C=C) (ring1),υ(C=C) (ring3)48

28

1570.81

υ(C=C) (ring1),υ(C=C) (ring3)56

29

1553.82

υ(C=C) (ring2), υ(C=C) (ring4)55

30

1553.69

υ(C=C) (ring2), υ(C=C) (ring4)56

31

1538.38

υ(C=C) (ring1), υ(C=C) (ring3)57

32

1538.36

υ(C=C) (ring1), υ(C=C) (ring3)59

33

1516.75

υ(C=C) (ring2), υ(C=C) (ring4)67

34

1516.73

35

1457.96

36

1457.64

β(C24H2), β(C59H2)82 Out of phase

37

1426.14

β(H35-O34-C32), β(H70-O69-C67)22

38

1422.86

υ(C=C) (ring1), υ(C=C) (ring3)27

39

1422.78

υ(C=C) (ring1), υ(C=C) (ring3)30

1498

υ(C=C) (ring2), υ(C=C) (ring4)54 1440

β(C24H2), β(C59H2)82 In-phase

40

1402.02

υ(C=C) (ring2), υ(C=C) (ring4)23

41

1401.51

υ(C=C) (ring2), υ(C=C) (ring4)10

42

1396.35

β(H28-C27-N29), β(H63-C62-N64)16, υ(C27-C32), υ(C62-C67)25

43

1369.44

υ(C=C) (ring2), υ(C=C) (ring4)16

44

1369.30

β(H28-C27-N29)28

45

1367.02

υ(C=C) (ring1), υ(C=C) (ring3)23

46

1367.00

υ(C=C) (ring1), υ(C=C) (ring3)11

47

1348.65

β(H28-C27-N29), β(H63-C62-N64)62, β(H30-N29-C27), β(H65-N64-C62)15

48

1345.48

β(H28-C27-N29), β(H63-C62-N64)44, β(H30-C29-N27), β(H65-C64-N62)14

49

1315.21

υ(C3-O22)28

50

1315.13

υ(C32-O)25

51

1312.30

52

1312.25

53

1286.30

υ(C=C) (ring2), υ(C=C) (ring4)47

54

1285.43

υ(C=C) (ring2), υ(C=C) (ring4)45

55

1272.06

υ(C=C) (ring2), υ(C=C) (ring4)11, β(H35-O34-C32), β(H70-O69-C67)12,

υ(C=C) (ring1), υ(C=C) (ring3)54, β(H23-O22-C3), β(H58-O57-C38)17

1316 1309

υ(C=C) (ring1), υ(C=C) (ring3)46, β(H23-O22-C3), β(H58-O57-C38)25

υ(C32-O), υ(C67-O)15 56

1266.99

υ(C32-O), υ(C67-O)17

57

1252.87

β(H7-C1-C6), β(H42-C36-C41)18, υ(C6-O), υ(C3-O), υ(C41-O), υ(C38-O)57

58

1252.85

59

1244.72

β(H25-C24-C9), β(H60-C59-C44)10

60

1244.39

β(H30-C29-N27), β(H65-C64-N62)23, β(H30-N29-C27), β(H65-N64-C62)21

1248

β(H7-C1-C6), β(H42-C36-C41)17, υ(C6-O), υ(C3-O), υ(C41-O), υ(C38-O)51

61

1220.60

1230

υ(C3-O), υ(C41-O)15, β(H7-C1-C6), β(H42-C36-C41)13, β(H23-O22-C3), β(H58-O57-C38)10

62

1220.53

υ(C6-O), υ(C3-O), υ(C41-O), υ(C38-O)11, υ(C12-O), υ(C47-O)13

63

1220.09

υ(C12-O), υ(C47-O)13

64

1215.05

υ(C32-O), υ(C67-O)21

65

1199.68

υ(C6-O17), υ(C41-O52)10, β(H8-C5-C6)15, υ(C9-C24), υ(C44-C59)14

66

1199.58

β(H8-C5-C6), β(H43-C40-C41)16, υ(C9-C24), υ(C44-C59)14

67

1194.22

β(H15-C10-C11), β(H50-C45-C46)44

68

1194.18

β(H15-C10-C11), β(H50-C45-C46)42

69

1185.26

υ(C9-C24), υ(C44-C59)10, β(H16-C14-C13), β(H51-C49-C48)48

70

1185.22

71

1151.71

72

1151.66

73

1133.25

1180

υ(C9-C24), υ(C44-C59)10, β(H16-C14-C13), β(H51-C49-C48)46 β(H8-C5-C6), β(H43-C40-C41)15, υ(C6-O), υ(C3-O), υ(C41-O), υ(C38-O)28

1162 1143

β(H8-C5-C6), β(H43-C40-C41)14, υ(C6-O), υ(C3-O), υ(C41-O), υ(C38-O)33 τ(H35-O34-C32-C27), τ(C32-O33-H70-O69), τ(C67-O69-H70-O33)40, τ(H35O34-C32-C27), τ(C32-O33-H70-O69), τ(C67-O69-H70-O33)36

1120

β(H30-N29-C27), β(H65-N64-C62)29, β(H25-C24-C9), β(H60-C59-C44)29

74

1110.85

75

1109.56

β(H23-O22-C3), β(H58-O57-C38)47

76

1109.53

β(H23-O22-C3), β(H58-O57-C38)27

77

1108.73

β(H25-C24-C9), β(H60-C59-C44)31, υ(C6-O), υ(C3-O), υ(C41-O), υ(C38O)12, β(H30-C29-N27), β(H65-C64-N62)26, β(H23-O22-C3), β(H58-O57C38)46

78

1098.08

υ(C27-N), υ(C62-N)39, τ(H35-O34-C32-C27)10, υ(C27-C24), υ(C62-C59)10

79

1090.24

υ(C27-C24), υ(C62-C59),υ(C27-N), υ(C62-N)59

80

1086.92

υ(C27-N), υ(C62-N)18, τ(H35-O34-C32-C27)19, τ(H70-O33-C32-C27), τ(H70O69-C67-C62)20, τ(H35-O34-C32-C27), τ(C32-O33-H70-O69), τ(C67-O69-H70O33)14

81

1024.09

υ(C12-O), υ(C47-O)11, β(C9-C10-C11), β(C9-C14-C13), β(C10-C9-C14),

1054

β(C44-C45-C46), β(C44-C49-C48), β(C45-C44-C49)59 82

υ(C12-O), υ(C47-O)11, β(C9-C10-C11), β(C9-C14-C13), β(C10-C9-C14),

1024.08

β(C44-C45-C46), β(C44-C49-C48), β(C45-C44-C49)44 83

β(H8-C5-C6), β(H43-C40-C41)11, β(C1-C6-C5), β(C2-C1-C6), β(C4-C5-C6),

1013.74

β(C36-C41-C40), β(C37-C36-C41), β(C39-C40-C41)74 84

β(H8-C5-C6), β(H43-C40-C41)11, β(C2-C1-C6), β(C4-C5-C6), β(C36-C41-

1013.73

C40), β(C37-C36-C41)25 85

964.08

970

979

β(H30-C29-N27), β(H65-C64-N62)12, υ(C27-C24), υ(C62-C59),υ(C27-N), υ(C62-N)15, τ(H7-C1-C2-C3)20 β(H30-N29-C27), β(H65-N64-C62)12, υ(C27-C24), υ(C62-C59)19

86

962.48

87

913.51

88

912.98

τ(H16-C14-C13-C12)24, τ(H51-C49-C48-C47)34

89

905.83

τ(H50-C45-C46-C47)29, τ(H15-C10-C11-C12)28, τ(C9-C10-C11-C12), τ(C44-

916

τ(H16-C14-C13-C12)31, τ(H51-C49-C48-C47)21

C45-C46-C47)11 90

905.42

τ(H50-C45-C46-C47)29, τ(H15-C10-C11-C12)29

91

887.48

τ(H42-C36-C41-C40)56,τ(H7-C1-C6-C5)19, τ(H43-C40-C41-C36)11

92

887.46

τ(H42-C36-C41-C40)19, τ(H7-C1-C6-C5)56, τ(H8-C5-C6-C1)11

93

881.82

β(C10-C9-C14),β(C44-C49-C48), β(C45-C44-C49)11

94

881.74

β(C9-C10-C11), β(C9-C14-C13), β(C10-C9-C14), β(C44-C45-C46), β(C44-C49C48), β(C45-C44-C49)11

95

τ(H43-C40-C41-C36)47, τ(H8-C5-C6-C1)18, γ(C1-C5-O17-C6), γ(C36-C40-

877.62

O52-C41)12 96

τ(H43-C40-C41-C36)18, τ(H8-C5-C6-C1)47, γ(C1-C5-O17-C6), γ(C36-C40-

877.60

O52-C41)12 97

865.62

υ(C27-C24), υ(C62-C59), υ(C27-N), υ(C62-N)55

98

865.18

υ(C27-N), υ(C62-N)13

99

855.13

υ(C32-C27)10, β(C2- C1-C6), β(C4- C5-C6)25

100

854.92

101

839.47

υ(C27-C32), υ(C62-C67)23

102

838.84

υ(C27-C32), υ(C62-C67)19

103

790.14

854

υ(C32-C27)18, β(C2- C1-C6), β(C4- C5-C6)12

β(C2-C1-C6), β(C1-C6-C5), β(C4-C5-C6), β(C36-C41-C40), β(C37-C36-C41),

806

β(C39-C40-C41)34 104

789.77

105

754.68

781 770

β(C1-C6-C5), β(C36-C41-C40)17 γ(O17-C11-C13-C12), γ(O52-C46-C48-C47)26, β(C6-O17-C12), β(C41-O52C47)12

106

754.67

γ(O17-C11-C13-C12), γ(O52-C46-C48-C47)25, β(C6-O17-C12), β(C41-O52C47)12

107

717.29

τ(C3-C2-C1-C6), τ(C38-C37-C36-C41), γ(O57-C37-C38-C38), γ(O22-C2-C4C3)64, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(I53-C38-C40-C39), γ(I54-C36-C38-

C37)10 108

717.28

γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)10

109

716.34

γ(O34-C27-O33-C32)11

110

713.54

111

699.28

γ(O34-C27-O33-C32)11, γ(O68-C62-O69-C32)12

112

694.01

β(C2-C1-C6), β(C4-C5-C6), β(C36-C41-C40), β(C37-C36-C41)15

113

687.26

β(C2-C1-C6), β(C4-C5-C6), β(C37-C36-C41), β(C39-C40-C41)17, β(O33-C32-

707

γ(O34-C27-O33-C32)11

O34)11 114

υ(C13-I), υ(C48-I)20, β(C9-C10-C11), β(C9-C14-C13), β(C44-C45-C46),

680.41

β(C44-C49-C48)44 115

680.35

676

υ(C11-I), υ(C46-I)22, β(C9-C10-C11), β(C9-C14-C13), β(C44-C45-C46), β(C44-C49-C48)46

116

675.67

υ(C39-I53), υ(C37-I54)13, β(C37-C36-C41), β(C39-C40-C41)24

117

664.68

υ(C2-I19), υ(C4-I18)10, β(C2-C1-C6), β(C4-C5-C6)15

118

662.02

τ(H30-N29-C27-C24), τ(H31-N29-C27-C24)20

119

627.80

τ(H30-N29-C27-C24), τ(H31-N29-C27-C24)25

120

625.26

β(O33-C32-O34)15, β(O68-C67-O69)10, τ(H30-N29-C27-C24), τ(H31-N29-C27C24)

121

604.20

γ(C24-C10-C14-C9), τ(H70-O69-C67-C62)15

122

600.74

γ(C24-C10-C14-C9), τ(H70-O69-C67-C62)20

123

568.74

τ(C3-C2-C1-C6), τ(C38-C37-C36-C41), γ(O57-C37-C38-C38), γ(O22-C2-C4C3)37

124

τ(C2-C1-C6-C5), τ(C37-C36-C41-C40)10, γ(C1-C5-O17-C6), γ(C36-C40-O52-

568.52

C41)28, γ(C1-C5-O17-C6), γ(C36-C40-O52-C41)27 125

β(C4-C3-O22), β(C39-C38-O57)11, β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-

564.36

I20), β(C40-C39-I53), β(C45-C46-I56), β(C49-C48-I55), β(C5-C6-O17), β(C40C41-O52)14 126

559.87

127

528.32

557

β(C4-C3-O22), β(C39-C38-O57)13, β(C5-C6-O17), β(C40-C41-O52)13 υ(C27-C32), υ(C62-C67)12, β(O68-C67-O69)16, β(C10-C11-I21), β(C14-C13I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12-O17), β(C27-C32-O33), β(C48-C47-O52), β(C62-C67-O69)

128

υ(C27-C32), υ(C62-C67), υ(C32-O33), υ(C67-O68)11, β(O68-C67-O69)13,

526.01

β(C27-C32-O33), β(C62-C67-O69)17 129

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12-

509.04

O17), β(C14-C9-C24), β(C48-C47-O52), β(C49-C44-C59)62 130

508.63

504

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12O17), β(C48-C47-O52)64

131

497.42

β(C4-C3-O22), β(C39-C38-O57)30

132

497.19

β(C4-C3-O22), β(C39-C38-O57)30

133

494.45

γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47C46)47

134

494.25

γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47C46)41

135

485.67

τ(C2-C1-C6-C5), τ(C37-C36-C41-C40)13, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2),

γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)50 136

τ(C1-C6-C5-C4)12, τ(C36-C41-C40-C39)13, τ(C2-C1-C6-C5), τ(C37-C36-C41-

485.66

C40)13, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(I53-C38-C40-C39), γ(I54-C36C38-C37)49 137

472.78

γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)44

138

472.15

γ(I18-C3-C5-C4), γ(I19-C1-C3-C2)48

139

401.66

140

399.41

β(C24-C27-N29), β(C59-C62-N64)31

141

360.48

γ(N29-C24-C32-C27), γ(N64-C59-C67-C62)10, β(C5-C4-I18) β(C10-C11-I21),

411

β(C24-C27-N29), β(C59-C62-N64)29

β(C14-C13-I20), β(C40-C39-I53), β(C45-C46-I56), β(C49-C48-I55), β(C5-C6O17), β(C40-C41-O52)14 142

357.40

τ(C3-C2-C1-C6), τ(C38-C37-C36-C41), γ(O57-C37-C38-C38), γ(O22-C2-C4C3)57, γ(C1-C5-O17-C6), γ(C36-C40-O52-C41)16

143

356.50

γ(C1-C5-O17-C6), γ(C36-C40-O52-C41)18

144

351.69

τ(C3-C2-C1-C6), τ(C38-C37-C36-C41), γ(O57-C37-C38-C38), γ(O22-C2-C4C3)11, β(C5-C6-O17), β(C40-C41-O52)11, τ(H23-O22-C3-C2), τ(H58-O57C38-C37)14

145

347.68

τ(H23-O22-C3-C2), τ(H58-O57-C38-C37)88

146

347.12

τ(H23-O22-C3-C2), τ(H58-O57-C38-C37)78

147

343.01

τ(C3-C2-C1-C6), τ(C38-C37-C36-C41), γ(O57-C37-C38-C38), γ(O22-C2-C4C3)13

334

β(C24-C27-N29), β(C59-C62-N64)12

148

334.40

149

330.26

β(C13-C12-O17), β(C24-C27-N29)18

150

329.87

τ(H30-N29-C27-C24), τ(H31-N29- C27-C24)34

151

327.64

β(C24-C27-N29), β(C59-C62-N64)18

152

285.47

β(C27-C32-O33), β(C62-C67-O69)37, γ(N29-C24-C32-C27), γ(N64-C59-C67C62)25 270

β(C67-C62-N64)41, γ(C67-C59-N64-C62)15

153

257.08

154

256.86

τ(H30-N29-C27-C24), τ(H31-N29-C27-C24)67

155

253.85

β(C9-C24-C27), β(C44-C59-C62)10

156

250.23

τ(H30-N29-C27-C24),τ(H31-N29-C27-C24)21

157

237.76

β(C4-C3-O22), β(C39-C38-O57)20

158

236.72

β(C4-C3-O22), β(C39-C38-O57)17, β(C1-C2-I19), β(C5-C4-I18) β(C10-C11I21), β(C14-C13-I20), β(C36-C37-I54), β(C40-C39-I53) β(C45-C46-I56), β(C49C48-I55)55

159

229.16

β(C9-C10-C11), β(C9-C14-C13), β(C44-C45-C46), β(C44-C49-C48)10, β(C10C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12-O17), β(C14-C9-C24), β(C48-C47-O52), β(C49-C44-C59)18

160

228.74

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12O17), β(C48-C47-O52)25

161

215.37

β(C13-C12-O17), β(C10-C11-I21)26

162

213.28

β(C14-C13-I20), β(C13-C12-O17)20

163

198.21

υ(O33-H70)20

164

191.91

τ(H65-N64-C62-C59)29, τ(H66-N64-C62-C59)24

165

184.78

γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47C46)15

166

τ(C2-C1-C6-C5), τ(C37-C36-C41-C40)34, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2),

176.85

γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)44 167

τ(C1-C6-C5-C4)14,τ(C36-C41-C40-C39)14, γ(I18-C3-C5-C4), γ(I19-C1-C3-

176.84

C2), γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)44 168

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12-

172.81

O17), β(C27-C32-O33), β(C14-C9-C24), β(C48-C47-O52), β(C62-C67-O69), β(C49-C44-C59)13, γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49C48), γ(I56-C45-C47-C46)13 169

γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47-

170.12

C46)32 170

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12-

167.75

O17), β(C27-C32-O33), β(C48-C47-O52), β(C62-C67-O69), β(C49-C44-C59)14, γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47C46)27 171

165.63

156

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12O17), β(C48-C47-O52), β(C49-C44-C59)15

172

165.15

γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47C46)14

173

137.40

β(H35-O34-C32), β(H70-O69-C67)14, β(H70-O33-C32)21

174

125.05

β(C1-C2-I19), β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-I20), β(C36-C37-I54), β(C40-C39-I53) β(C45-C46-I56), β(C49-C48-I55)16

175

119.80

τ(C2-C1-C6-C5), τ(C37-C36-C41-C40)13, γ(C1-C5-O17-C6), γ(C36-C40-O52C41)18, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(I53-C38-C40-C39), γ(I54-C36C38-C37)16

176

117.50

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12O17), β(C14-C9-C24), β(C48-C47-O52), β(C49-C44-C59)25, γ(C1-C5-O17-C6), γ(C36-C40-O52-C41)17, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(I53-C38-C40C39), γ(I54-C36-C38-C37)16, τ(C2-C1-C6-C5), τ(C37-C36-C41-C40)13

177

113.26

β(C1-C2-I19), β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-I20), β(C36-C37-I54), β(C40-C39-I53) β(C45-C46-I56), β(C49-C48-I55) β(C5-C6-O17), β(C40-C41O52)35

178

107.33

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12O17), β(C27-C32-O33), β(C14-C9-C24), β(C48-C47-O52), β(C62-C67-O69)39

179

101.83

τ(H35-O34-C32-C27), τ(C32-O33-H70-O69), τ(C67-O69-H70-O33)40,τ(H70-O33C32-C27), τ(H70-O69-C67-C62)14, β(C1-C2-I19), β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-I20), β(C36-C37-I54), β(C40-C39-I53) β(C45-C46-I56), β(C49-C48I55)19

180

100.62

τ(H35-O34-C32-C27), τ(C32-O33-H70-O69), τ(C67-O69-H70-O33)18, β(C1-C2I19), β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-I20), β(C36-C37-I54), β(C40C39-I53) β(C45-C46-I56), β(C49-C48-I55)44

181

100.00

β(C1-C2-I19), β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-I20), β(C36-C37-I54),

β(C40-C39-I53) β(C45-C46-I56), β(C49-C48-I55)57 182

88.02

β(C1-C2-I19), β(C5-C4-I18) β(C10-C11-I21), β(C14-C13-I20), β(C36-C37-I54), β(C40-C39-I53) β(C45-C46-I56), β(C49-C48-I55)13

183

75.01

τ(H70-O33-C32-C27), τ(H70-O69-C67-C62)16

184

71.88

τ(C3-C2-C1-C6), τ(C38-C37-C36-C41)17, γ(O57-C37-C38-C38), γ(O22-C2-C4C3)34, τ(C2-C1-C6-C5), τ(C37-C36-C41-C40)17, γ(I18-C3-C5-C4), γ(I19-C1C3-C2), γ(I53-C38-C40-C39), γ(I54-C36-C38-C37)39

185

71.87

τ(C36-C41-C40-C39)10, γ(I18-C3-C5-C4), γ(I19-C1-C3-C2), γ(I53-C38-C40C39), γ(I54-C36-C38-C37)39

186

68.53

β(C5-C4-I18), β(C10-C11-I21), β(C14-C13-I20), β(C40-C39-I53), β(C45-C46I56), β(C49-C48-I55), β(C5-C6-O17), β(C40-C41-O52)65

187

68.49

β(C5-C4-I18), β(C10-C11-I21), β(C14-C13-I20), β(C40-C39-I53), β(C45-C46I56), β(C49-C48-I55)65

188

46.95

β(C6-O17-C12), β(C41-O52-C47)12, τ(H70-O33-C32-C27), τ(H70-O69-C67C62)16

189

42.15

γ(I20-C12-C14-C13), γ(I21-C10-C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47C46)27

190

40.75

τ(C9-C10-C11-C12), τ(C44-C45-C46-C47)19, γ(I20-C12-C14-C13), γ(I21-C10C12-C11), γ(I55-C47-C49-C48), γ(I56-C45-C47-C46)30

191

37.36

β(C6-O17-C12), β(C41-O52-C47)15

192

34.04

τ(C9-C24-C27-C32), τ(C10-C9-C24-C27), τ(C44-C59-C62-C67), τ(C49-C44-C59C62), τ(C24-C27-C32-O33), τ(C59-C62-C67-O69)70

193

29.63

β(C10-C11-I21), β(C14-C13-I20), β(C45-C46-I56), β(C49-C48-I55), β(C13-C12O17), β(C14-C9-C24), β(C48-C47-O52), β(C49-C44-C59)12, τ(C24-C27-C32O33), τ(C59-C62-C67-O69)12, τ(C9-C24-C27-C32), τ(C44-C59-C62-C67)13, τ(C10-C9-C24-C27), τ(C49-C44-C59-C62)24

194

20.85

β(C6-O17-C12), β(C41-O52-C47)11, τ(C24-C27-C32-O33), τ(C59-C62-C67O69)25, τ(C9-C24-C27-C32), τ(C44-C59-C62-C67)25

195

19.49

τ(C9-C24-C27-C32), τ(C10-C9-C24-C27), τ(C44-C59-C62-C67), τ(C49-C44-C59C62), τ(C24-C27-C32-O33), τ(C59-C62-C67-O69)55

196

13.36

τ(C6-O17-C12-C11), τ(C41-O52-C47-C46)58

197

12.90

τ(C6-O17-C12-C11), τ(C41-O52-C47-C46)53

198

10.55

γ(O17-C11-C13-C12), γ(O52-C46-C48-C47)10, τ(C9-C24-C27-C32), τ(C44-C59C62-C67)22, τ(C6-O17-C12-C11), τ(C41-O52-C47-C46)10, τ(C5-C6-O17-C12), τ(C40-C41-O52-C47)13

199

10.29

β(C6-O17-C12), β(C41-O52-C47)10, τ(C6-O17-C12-C11), τ(C41-O52-C47C46)17, τ(C5-C6-O17-C12), τ(C40-C41-O52-C47)12

200

7.56

τ(C5-C6-O17-C12), τ(C40-C41-O52-C47)67

201

7.01

τ(C5-C6-O17-C12), τ(C40-C41-O52-C47)64

202

4.22

τ(C24-C27-C32-O33), τ(C59-C62-C67-O69)13, τ(C9-C24-C27-C32), τ(C10-C9C24-C27), τ(C44-C59-C62-C67), τ(C49-C44-C59-C62)

203

3.70

τ(H70-O33-C32-C27), τ(H70-O69-C67-C62)25, τ(H35-O34-C32-C27), τ(C32O33-H70-O69), τ(C67-O69-H70-O33)12

204

2.13

τ(H70-O33-C32-C27), τ(H70-O69-C67-C62)18, τ(C24-C27-C32-O33), τ(C59-C62-

C67-O69)16, τ(C10-C9-C24-C27), τ(C49-C44-C59-C62)33 7c. The experimental and theoretical peak frequencies assigned for Thyroxine cyclic dimer