Conformational, structural, vibrational, electronic and quantum chemical investigations of cis-2-methoxycinnamic acid

Journal of Molecular Structure 1080 (2015) 122–136

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Conformational, structural, vibrational, electronic and quantum chemical investigations of cis-2-methoxycinnamic acid V. Arjunan a,⇑, R. Anitha b, M.K. Marchewka c, S. Mohan d, Haifeng Yang e a

Department of Chemistry, Arignar Anna Government Arts & Science College, Karaikal 609 605, India Department of Chemistry, Kanchi Mamunivar Centre for Post-Graduate Studies, Puducherry 605 008, India c Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Wroclaw, Poland d School of Sciences and Humanities, Vel Tech University, Avadi, Chennai 600 062, India e Department of Chemistry, Shanghai Normal University, Shanghai 200234, China b

h i g h l i g h t s

g r a p h i c a l a b s t r a c t

 Spectral properties of cis-2-

methoxycinnamic acid have been studied.  The more stable conformations of the molecule are determined.  The stable structure has C@O and C@C bond in s-cis orientation.  The barrier height between more and less stable conformer is 2.43 kcal mol1.  The MEP has the range +1.140e  102 to 1.140e  102.

a r t i c l e

i n f o

Article history: Received 25 July 2014 Received in revised form 26 September 2014 Accepted 26 September 2014 Available online 5 October 2014 Keywords: FTIR FT-Raman NMR cis-2-Methoxycinnamic acid DFT NBO

a b s t r a c t The Fourier transform infrared (FTIR) and FT-Raman spectra of cis-2-methoxycinnamic acid have been measured in the range 4000–400 and 4000–100 cm1, respectively. Complete vibrational assignment and analysis of the fundamental modes of the compound were carried out using the observed FTIR and FT-Raman data. The geometry was optimised without any symmetry constrains using the DFT/ B3LYP method utilising 6-311++G⁄⁄ and cc-pVTZ basis sets. The thermodynamic stability and chemical reactivity descriptors of the molecule have been determined. The exact environment of C and H of the molecule has been analysed by NMR spectroscopies through 1H and 13C NMR chemical shifts of the molecule. The energies of the frontier molecular orbitals have also been determined. Complete NBO analysis was also carried out to find out the intramolecular electronic interactions and their stabilisation energy. The vibrational frequencies which were determined experimentally are compared with those obtained theoretically from density functional theory (DFT) gradient calculations employing the B3LYP/6311++G⁄⁄ and cc-pVTZ methods. Ó 2014 Elsevier B.V. All rights reserved.

Introduction

⇑ Corresponding author. Tel.: +91 413 2211111, mobile: +91 9442992223; fax: +91 413 2251613. E-mail address: [email protected] (V. Arjunan). http://dx.doi.org/10.1016/j.molstruc.2014.09.083 0022-2860/Ó 2014 Elsevier B.V. All rights reserved.

Phenolic acid derivatives constitute a group of natural compounds present in human diet in significant amounts, which have long been known to display both antioxidant (through their radical scavenging activity) and prooxidant properties [1–3]. They are

V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136

involved in numerous metabolic reactions and are naturally occurring in many plant-derived food products, largely responsible for the browning process [4–6]. Apart from being widely used as antioxidant food additives [7,8], some of them were lately found to behave as inhibitors of deleterious oxidative processes; e.g. in the prevention of cardiovascular diseases and inflammatory processes [9,10], or even in cancer [11–17]. Cinnamic acid (3-phenyl-2-propenoic acid), possesses antibacterial, antifungal and parasite fighting abilities [18,19]. The derivatives of cinnamic acid are important pharmaceutical agents for high blood pressure and stroke prevention and possess antitumour activities [20]. The biochemical properties of polyphenolic secondary plant metabolites such as esters of cinnamic acids (caffeic, ferulic, p- and o-coumaric, sinapic acid) attract much attention in biology and medicine. These compounds show antiviral, antibacterial, vasoactive, antiinflammatory and other properties. Cinnamic acids play vital role in the synthesis of other important compounds. It posses antitumour activity against Sarcoma 180 as well as antimicrobial activity [21]. Cinnamic acid is a fragrance ingredient used in many fragrance compounds. It may be found in fragrances used in decorative cosmetics, fine fragrances, shampoos, toilet soaps and other toiletries as well as in non-cosmetic products such as household cleaners and detergents. The effect of alkali metals (Li ? Na ? K ? Rb ? Cs) on the electronic structure of cinnamic acid) was studied by FTIR, FT-Raman and NMR spectroscopic techniques [22]. The investigation of the polarised IR spectra of cinnamic acid and of its deuterium derivative crystals have been reported [23]. The IR and Raman spectra of the two polymorphic forms (58°- and 68°-forms) of cis-cinnamic acid were measured and the spectral differences discussed on the basis of the crystal structures of the two forms [24]. Hydrogen bonded networks of methoxy-substituted a-phenylcinnamic acids studied by spectroscopic and computational methods [25]. Infrared and Raman spectroscopies have been used to monitor the [2 + 2] photodimerisation reactions of a-trans-cinnamic acid and of a number of its derivatives [26]. Trimerisation of E- and Z-a-phenylcinnamic acid was investigated by semiempirical quantum chemical methods [27]. Various F-substituted E-2,3-diphenyl propenoic acid molecules were synthesised and their aggregation behaviour was studied by experimental (FT-IR spectroscopy) and computational (semiempirical and DFT) methods [28]. The molecular packing in p-hydroxycinnamic acid has been determined by singlecrystal X-ray analysis in order to establish the role played by hydrogen bonding in inhibiting esophase formation [29]. Owing to the complexity of the molecule, the normal coordinate analysis is carried out to obtain complete informations of the molecular motions involved in the normal modes of 8H5NQ and also to calculate the potential energy distribution of the vibrational modes of the compound utilising Wilson’s FG matrix method [30–32]. The normal coordinate calculations were performed with the program of Fuhrer et al. [33]. In the molecule of cis-2-methoxycinnamic acid the carboxylic group is separated from the aromatic ring by a double bond. It causes conjugation between the double bond and the p-electron system. In the present investigation owing to the biological significance and non-availability of the structural, electronic and spectral details of cis-2-methoxycinnamic acid (cis-2MCA) in the literature, we have undertaken the complete structural and spectroscopic investigations of the molecule.

123

Fig. 1. The structure and atom numbering scheme of cis-2-methoxycinnamic acid.

KBr pellet method on a Bruker IFS 66V spectrometer equipped with a Globar source, Ge/KBr beam splitter and a TGS detector in the range of 4000–400 cm1. The spectral resolution is 2 cm1. The FT-Raman spectra of the compound are also recorded in the range 4000–100 cm1 using the same instrument with FRA 106 Raman module equipped with Nd:YAG laser source operating at 1.064 lm with 200 mW powers. A liquid nitrogen cooled-Ge detector was used. The frequencies of all sharp bands are accurate to 2 cm1. The 1H (400 MHz; CDCl3) and 13C (100 MHz; CDCl3) nuclear magnetic resonance (NMR) spectra are recorded on a Bruker HC400 instrument. Chemical shifts for protons are reported in parts per million scales (d scale) downfield from tetramethylsilane.

Computational details The density functional theory (DFT) [34] with three parameter hybrid functional (B3) [35,36] for the exchange part and the Lee– Yang–Parr (LYP) correlation functional [37] have been utilised for the molecular geometry optimisation and then by computation of molecular structural parameters, vibrational frequencies, thermodynamic properties and energies of the optimised structure using the standard 6-311++G⁄⁄ and high level cc-pVTZ basis sets.

Experimental The compound cis-2MCA is purchased from Aldrich chemicals, U.S.A., and is used as such to record the FTIR, FT-Raman and NMR spectra. The FTIR spectrum of the compound is recorded by

Fig. 2. Potential energy profile of cis-2-methoxycinnamic acid showing the orientation of the ACH@CHACOOH group.

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V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136

Gaussian-09 [23] program, invoking gradient geometry optimisation [38]. The Raman scattering activities (Si) are converted to relative Raman intensities (Ii) using the following relationship derived from the basic theory of Raman scattering [39].

Ii ¼

Fig. 3. Potential energy profile of cis-2-methoxycinnamic acid showing the orientation of the ACOOH group.

f ðm0  mi Þ4 Si mi ½1  expðhcmi =kTÞ

where m0 is the exciting frequency (cm1), vi is the vibrational wavenumber of the ith normal mode, h, c and k are universal constants, and f is the suitably chosen common scaling factor for all the peak intensities. Isoelectronic molecular electrostatic potential surface (MEP) and electron density surface [40] are constructed using 6-311++G⁄⁄ and cc-pVTZ basis sets. The molecular electrostatic potential (MEP) at a point ‘r’ in the space around a molecule (in atomic units) can be expressed as:

VðrÞ ¼ The effects of electron correlation on the geometry optimisation have been taken into account. Theoretically the vibrational wavenumbers and their intensities are calculated in order to provide more information for the vibrational assignments of cis-2MCA. The quantum chemical calculations have been performed with

X A

Z  A   ! ! RA  r   

Z

!

q ðr0 Þdr0 !0 ! r  r   

where ZA is the charge on nucleus A, located at RA and q(r0 ) is the electronic density function for the molecule. The first and second terms represent the contributions to the potential due to nuclei

Fig. 4. The possible conformations of cis-2-methoxycinnamic acid.

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V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136 Table 1 Structural parameters of cis-2-methoxycinnamic acid (cis-2MCA) determined by B3LYP method with 6-311++G⁄⁄ and cc-pVTZ basis sets. Structural parameters

cis-2-Methoxycinnamic acid ⁄⁄

B3LYP/6-311++G Bond length (Å) C1AC2 C1AC6 C1AC16 C2AC3 C2AO7 C3AC4 C3AH9 C4AC5 C4AH10 C5AC6 C5AH11 C6AH12 O7AC8 C8AH13 C8AH14 C8AH15 H12AO19 C16@C17 C16AH22 C17AC18 C17AH23 C18@O19 C18AO20 O20AH21 R2 Bond angle (°) C2AC1AC6 C2AC1AC16 C6AC1AC16 C1AC2AC3 C1AC2AO7 C3AC2AO7 C2AC3AC4 C2AC3AH9 C4AC3AH9 C3AC4AC5 C3AC4AH10 C5AC4AH10 C4AC5AC6 C4AC5AH11 C6AC5AH11 C1AC6AC5 C1AC6AH12 C5AC6AH12 C2AO7AC8 O7AC8AH13 O7AC8AH14 O7AC8AH15 H13AC8AH14 H13AC8AH15 H14AC8AH15 C1AC16AC17 C1AC16AH22 C17AC16AH22 C16AC17AC18 C16AC17AH23 C18AC17AH23 C17AC18AO19 C17AC18AO20 O19AC18AO20 C18AO20AH21 Dihedral angle (°) C3AC2AO7AC8 C1AC2AO7AC8 C1AC16AC17AC18 H22AC16AC17AC18 C1AC16AC17AH23 C16AC17AC18AO19 C16AC17AC18AO20 C16AC17AC1AC2 C17AC18AO20AH21 a

1.42 1.40 1.46 1.39 1.36 1.39 1.08 1.39 1.08 1.39 1.08 1.08 1.42 1.09 1.09 1.09 2.03 1.35 1.08 1.47 1.08 1.21 1.36 0.97 0.995

B3LYP/cc-pVTZ 1.42 1.40 1.46 1.39 1.36 1.39 1.08 1.39 1.08 1.39 1.08 1.08 1.42 1.09 1.09 1.09 2.03 1.35 1.08 1.47 1.08 1.21 1.36 0.97 0.995

117.4 117.4 125.2 120.6 116.8 122.6 120.1 120.5 119.4 120.4 119.2 120.4 119.8 120.4 119.8 121.7 118.2 120.1 119.3 105.8 111.4 111.4 109.3 109.3 109.4 135.9 111.7 112.4 132.0 115.8 112.2 129.8 109.7 120.5 106.1

117.4 117.4 125.2 120.6 116.8 122.6 120.1 120.5 119.4 120.4 119.2 120.4 119.8 120.4 119.8 121.7 118.2 120.1 119.3 105.8 111.4 111.4 109.3 109.3 109.4 135.9 111.7 112.4 132.0 115.8 112.2 129.8 109.7 120.5 106.1

0.0 180.0 0.0 180.0 180.0 0.0 180.0 180.0 180.0

0.0 180.0 0.0 180.0 180.0 0.0 180.0 180.0 180.0

Values taken from Ref. [48].

Experimentala

1.404 1.402 1.463 1.391 1.394 1.080 1.395 1.080 1.393 1.080 1.080

1.345 1.080 1.469 1.080 1.245 1.309 1.010

118.6 119.0 122.4 120.4

120.4 119.3 120.2 119.7 120.6 119.8 120.0 120.9 119.1 120.8 120.8 118.4

and electrons, respectively. V(r) is the resultant electric potential at each point r, which is the net electrostatic effect produced at the point r by both the electrons and nuclei of the molecule. The molecular electrostatic potential (MEP) serves as a useful quantity to explain hydrogen bonding, reactivity and structure-activity relationship of biomolecules and drugs [41]. Structures resulting from the plot of electron density surface mapped with electrostatic potential surface depict the shape, size, charge density distribution and the site of chemical reactivity of a molecule. GaussView 5.0.8 visualisation program [42] has been utilised to construct the MEP surface, the shape of highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbitals. The 1H and 13C NMR isotropic shielding constants are calculated using the GIAO method [43,44] using the optimised parameters obtained from B3LYP/6-311++G⁄⁄ method. The effect of solvent on the theoretical NMR parameters is included using the PCM model. The isotropic shielding constant values are used to calculate the isotropic chemical shifts d with respect to tetramethylsilane (TMS) using the relation diso (X) = riso TMS (X)  riso (X), where diso is the isotropic chemical shift and riso is the isotropic shielding constant. Various reactivity and selectivity descriptors such as chemical hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local quantities employing natural population analysis (NPA) are calculated. Both the global and local reactivity descriptors are determined using finite difference approximation to reveal the reactivity of the molecule. The vertical ionisation potential (I), electron affinity (A) and the electron populations are determined on the basis of B3LYP/cc-pVTZ method. The energy calculations of the N-electron species are done using restricted B3LYP method while the energies of the N  1 and N + 1 electronic species were calculated using open shell restricted B3LYP method using B3LYP/cc-pVTZ optimised geometry of the Nelectron species. The site-selectivity of a chemical system, can be determined by using Fukui functions [45,46] which can be interpreted either as the change of electron density q(r) at each point r when the total number of electrons is changed or as the sensitivity of chemical potential (l) of a system to an external perturbation at a particular point r.

f ðrÞ ¼

    @ qðrÞ dl ¼ @N v ðrÞ dv ðrÞ N

Yang and Parr introduced local softness s(r) to predict the reactivity [46]. The s(r) describes the sensitivity of the chemical potential of the system to the local external perturbation and is obtained by simply multiplying Fukui function f(r) with global softness S. 126.1 114.2 119.7 122.2 120.2 117.7 120.2 116.5 123.3 110.1

179.2 0.3 0.0 2.9 176.9 4.1 177.3

Table 2 The calculated thermodynamic parameters of cis-2-methoxycinnamic acid (cis-2MCA) by B3LYP method with 6-311++G⁄⁄ and cc-pVTZ basis sets. Thermodynamic parameters (298 K)

cis-2-Methoxycinnamic acid B3LYP/6311++G⁄⁄

SCF energy (Hartrees) 612.9195724 Total energy (thermal), Etotal (kcal mol1) 121.29 Vibrational energy, Evib (kcal mol1) 119.51 Zero point vibrational energy (kcal mol1) 113.83 Rotational constants (GHz) X Y Z

B3LYP/ccpVTZ 612.9710537 121.54 119.76 114.11

1.45 0.46 0.35

1.46 0.46 0.35

3.17 1.17 0.00 3.37

2.85 1.24 0.00 3.12

Dipole moment (Debye)

lx ly lz ltotal

Species Observed wavenumber (cm1) FTIR A0 A0 A0 A0 A0 A0 A0 A00 A0 A0

1455 s 1433 vs 1377 m 1312 s 1291 s 1263 vs 1246 vs 1221 s 1178 m 1169 m 1151 m 1107 s 1050 m 1023 s 946 s 859 vw 837 m 793 m

752 vs 730 m 682 w

3080 w 3051 w 3022 w

2950 vw 2889 vw

Unscaled (cm1) Scaled (cm1) IR intensity Raman activity 3757 3229 3214 3189 3189 3170 3169 3132 3070 3011

1771 1648 vs 1658 1602 m 1636 1611 1493 w 1524 1507 1499 1496 1489 1472 1309 m 1381 1329 1261 m 1320 1252 m 1299 1237 m 1274 1212 1181 m 1203 1192 1174 1129 vw 1144 1124 1063 w 1083 1046 w 1058 1041 1012 s 1020 967 w 982 933 851 m 882 839 m 848 826 783 w 791 769 vw 778 757 vw 778 740 687 vw 712

3437 3126 3083 3062 3047 3025 3012 2974 2953 2892

1698 1639 1602 1574 1493 1477 1455 1433 1377 1384 1312 1291 1263 1252 1236 1187 1177 1168 1150 1128 1106 1062 1045 1022 1011 966 913 858 836 792 782 768 756 728 685

99.32 43.63 8.00 16.60 8.13 5.24 0.58 17.91 32.47 59.87

184.64 226.11 114.70 0.64 33.54 56.33 13.44 7.54 77.68 56.51 55.62 23.67 31.94 14.67 226.77 10.27 8.08 7.21 1.13 469.24 307.75 12.03 57.90 0.04 0.81 1.94 2.81 1.08 47.49 8.84 1.31 21.93 57.13 0.58 10.31

20.78 7.49 16.01 24.66 12.00 13.67 2.24 12.99 8.95 21.71

5.88 48.68 100 1.56 10.20 0.47 1.55 1.56 5.89 0.84 26.58 2.32 2.58 1.26 6.73 4.53 1.06 4.57 0.20 1.31 8.90 3.88 2.08 0.61 0.01 0.00 0.54 0.03 0.11 1.36 0.12 1.73 0.01 0.60 0.20

Depolarisation ratio Assignment %PED

Unscaled (cm1) Scaled (cm1) IR intensity Raman activity 0.75 0.75 0.75 0.75 0.71 0.46 0.75 0.75 0.75 0.10

0.75 0.23 0.75 0.16 0.75 0.71 0.66 0.75 0.75 0.12 0.75 0.08 0.75 0.32 0.75 0.75 0.50 0.75 0.75 0.75 0.21 0.11 0.24 0.45 0.75 0.37 0.72 0.22 0.19 0.65 0.55 0.44 0.31 0.39 0.36

3774 3227 3210 3188 3188 3169 3169 3136 3073 3011

1764 1654 1633 1608 1518 1503 1493 1493 1483 1467 1378 1327 1312 1295 1269 1209 1199 1188 1167 1141 1120 1079 1053 1038 1016 970 931 872 841 822 786 775 773 738 708

3430 3120 3073 3056 3041 3019 3006 2969 2948 2887

1696 1637 1597 1572 1489 1468 1453 1431 1375 1345 1307 1289 1259 1250 1235 1180 1176 1167 1149 1127 1105 1061 1044 1021 1010 944 907 849 835 791 781 767 750 728 680

110.42 40.54 7.85 6.20 15.92 4.55 1.24 17.99 32.41 62.59

219.10 248.92 121.00 1.78 30.54 63.16 9.52 21.76 85.51 58.03 54.99 19.62 33.06 11.86 230.92 8.89 9.43 4.90 0.73 509.73 343.07 12.42 57.04 0.28 2.34 2.35 1.57 2.87 49.65 9.71 11.96 19.26 57.86 0.72 11.89

17.71 6.77 14.87 31.57 1.01 11.63 2.03 12.03 8.06 20.29

7.11 50.64 100 2.06 9.03 0.56 1.57 0.90 6.64 0.80 26.16 3.36 0.95 1.23 7.68 4.50 1.63 3.74 0.30 1.35 8.94 4.61 1.94 0.63 0.00 0.03 0.53 0.01 0.02 1.16 0.07 2.00 0.07 0.53 0.09

0.75 0.75 0.75 0.75 0.70 0.45 0.75 0.75 0.75 0.09

mOAH mCAH mCAH mCAH m@CAH m@CAH mCAH maCH3 maCH3 msCH3

87mOH 85mCH 82mCH 80mCH 84mCH 87mCH 81mCH 80mCH 81mCH 89mCH

0.75 0.26 0.09 0.75 0.26 0.69 0.75 0.65 0.75 0.11 0.75 0.05 0.75 0.35 0.75 0.75 0.54 0.75 0.75 0.75 0.19 0.08 0.26 0.51 0.75 0.32 0.58 0.19 0.15 0.61 0.72 0.44 0.29 0.43 0.38

2  1433 2  1312 2  1377 2  1291 2  1023 2  946 mC@O mC@C mCAC mCAC mCAC daCH3 daCH3 dsCH3 b@CAH mCAC b@CAH mCAC bOAH mCAC mCAO(CH3) mCAC mCAC mOA(CH3) xCH3 mCAO(H) bCAH bCAH sCH3 c@CAH bCAH bCAH bC@C cCAH c@CAH RB cCAH bC@O cCAH bCCC cCAH

85mCO 85mCC 85mCC 85mCC 85mCC 75dCH3 72dCH3 80dCH3 77bCH 71mCC 73bCH 75mCC 67bOH + 16bC@O 79mCC 74mCO 72mCC 75mCC 76mOC 60xCH3 + 25sCH3 73mCO 62bCH + 12bCCC 60bCH + 15bCCC 57sCH3 + 22xCH3 62cCH + 14cC@O 63bCH + 17bCCC 66bCH + 14bCCC 59bCC + 16bCH 52cCH + 18cCCC 55bCH + 18bCC 78bCCC 45cCH + 21cCCC 70bC@O + 13bCH 49cCH + 24cCCC 49bCCC + 16bCH 51cCH + 19cCCC

V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136

A0 A0 A0 A0 A0 A0 A00 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A00 A0 A0 A0 A0 A00 A0 A0 A0 A00 A00 A0 A00 A0 A00 A0 A00

3433 w 3123 w 3076 m 3059 m 3044 m 3029 m 3009 m 2971 m 2940 m 2876 m 2804 m 2733 w 2678 m 2583 m 2022 vw 1875 vw 1698 vs 1639 vs 1599 s 1574 m 1491 s

FTR

Depolarisation ratio B3LYP/6-311++G⁄⁄ calculated wavenumber

B3LYP/cc-pVTZ calculated wavenumber

126

Table 3 The observed FTIR, FT-Raman and calculated frequencies using B3LYP method with 6-311++G⁄⁄ and cc-pVTZ basis sets along with their relative intensities and probable assignments of cis-2-methoxycinnamic acid.a

V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136

127

69cC@O + 20cCC 61cOH + 18cC@O bCCC 47bCCC + 21bCH bCAOH 45bCO + 25bCH bO-C(H3) 52bOC + 26bCC bCAC 47bCC + 21bCH bCAOC(H3) 47bCO + 25bCCC bCAC 49bCC + 18bCH cCAOC(H3) 42cCO + 23cCCC cCCC 47cCCC + 19cCH cCCC 46cCCC + 21cCH cCCC 45cCCC + 25cCH cCCC 49cCCC + 29cCH cCCC 44cCCC + 24cCH cCAC 45cCC + 27cCH cOAC(H3) 46cOC + 23cCCC cCAO(H) 49cCO + 24cCH cCAC 43cCC + 29cCH

Both s(r) and f(r) contain the same information. The local softness values are generally used in predicting the reactivities such as electrophilic, nucleophilic and free radical reactions, and regioselectivity.

sðrÞ ¼



@ qðrÞ @l

 v ðrÞ

cC@O cOAH

sðrÞ ¼ f ðrÞS where S is the global softness which is inversely related to global hardness (g). Results and discussion

m – stretching; b – in-plane bending; d – deformation; q – rocking; c – out of plane bending; x – wagging and s – twisting/torsion. a

360 w 336 w 306 w 268 vw 223 w 194 w 162 w 124 vs

570 w 549 vw 519 m 491 m 577 w 538 w 514 m

477 m

610 m

A00 A00 A0 A0 A0 A0 A0 A0 A00 A00 A00 A00 A00 A00 A00 A00 A00 A00

603 m

612 598 589 543 531 480 469 370 331 278 260 227 196 141 134 91 45 15

601 584 575 536 517 489 475 358 334 304 266 220 191 159 121 85 42 12

71.97 1.16 43.55 0.16 26.47 17.23 2.57 2.97 0.91 0.15 2.52 0.06 2.40 1.17 0.71 4.23 2.16 0.05

1.01 2.50 0.19 0.08 0.09 0.01 0.26 0.33 0.98 0.07 0.18 0.10 0.68 0.20 0.25 0.04 0.00 0.13

0.75 0.33 0.45 0.37 0.56 0.35 0.23 0.32 0.03 0.75 0.51 0.61 0.63 0.19 0.27 0.19 0.19 0.28

597 592 587 537 530 474 467 365 330 273 259 223 196 142 134 85 44 19

601 575 575 536 512 489 475 358 334 304 266 221 192 160 122 78 38 14

1.71 80.45 43.28 0.31 27.73 22.15 2.83 3.22 1.11 0.29 2.72 0.06 2.20 1.08 0.90 5.00 2.20 0.06

2.44 0.48 0.26 0.01 0.11 0.03 0.26 0.28 1.05 0.02 0.19 0.11 0.63 0.18 0.16 0.05 0.00 0.09

0.39 0.75 0.11 0.39 0.55 0.36 0.21 0.35 0.03 0.75 0.50 0.66 0.63 0.09 0.25 0.18 0.17 0.25

Analysis of the potential energy profile The optimised structure of the compound cis-2MCA and the scheme of numbering the atoms is shown in Fig. 1. Molecular geometry is a sensitive indicator of intra and intermolecular interactions. Conformational analysis of the compound cis-2MCA is carried out by using B3LYP/6-31G⁄⁄ method to determine the exact orientations of the ACH@CHACOOH and ACOOH groups. Vibrational spectra and molecular structure are interconnected via molecular potential energy surfaces. The more stable structure is the geometry at equilibrium where the potential energy surface is minimum. All possible geometry of the conformers are optimised to find out the energetically and thermodynamically most stable configuration of the compound. The orientation of the acrylic acid chain relative to the aromatic ring is defined by dihedral (C17AC16AC1AC2). The initial value of the dihedral angle C2AC1AC16AC17 is set to zero and for every 10° the energies of the conformers are determined. The acrylyl group exhibits free rotation about C1AC16 bond to the phenyl ring. The potential energy surfaces of cis-2MCA obtained by the rotation of the acrylyl group with the dihedral angle C2AC1AC16AC17 is presented in Fig. 2. The conformer (I) with a (C17AC16AC1AC2) dihedral equal to 180° is found to be more favoured relative to the one (IV) with (C17AC16AC1AC2) = 0°, possibly due to both delocalisation and steric repulsion effects between the methoxy and acrylic acid groups. The variation in energy with rotation of the acrylyl group with respect to the phenyl ring found a single minimum corresponds to the structure of the molecule (I). The conformer (I) is 6.60 kcal mol1 more stable than the conformer with tilted structure (II). The exact dihedral angle (C17AC16AC1AC2) of the conformer (II) is 4.6° and is non-planar with respect to the phenyl ring. This is due to the repulsion between the ACOOH and AOCH3 groups. If the distance between these two groups increases the stability also increases. The conformer (II) with the dihedral angle (C17AC16AC1AC2) of 50° is 3.35 kcal mol1 more stable than (IV) and 3.25 kcal mol1 less stable than the conformer (I). After fixing the orientation of the ACH@CHACOOH group, the orientation of the ACOOH group has been determined by rotating the acid group along C17AC18 bond using the dihedral angle C16AC17AC18AO20. Potential energy profile of cis-2MCA acid showing the orientation of the ACOOH group is shown in Fig. 3. Vibrational frequencies, coordinates and interstices are reflecting the potential energy surface. In other words, potential energy surface which accurately predicts the stable geometry and equally precisely determine the vibrational spectra simultaneously. The pictorial representation of the possible conformers of cis-2MCA are given in Fig. 4. The orientation of the carboxylic moiety relative to the linear chain C@C bond is determined by the dihedral angle (O19AC18AC17AC16). The dihedral angle is equal to 0° or 180°, the former defining a cis- and the later is for trans- orientation,

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Fig. 6. Correlation of the experimental and theoretical scaled wavenumbers of cis2-methoxycinnamic acid.

conformer (a). The conformer (b) is non planar in which the ACH@CHACOOH group is moving away with respect to the plane of the phenyl ring. The barrier heights between the more stable conformer (a) and the less stable excited state conformers (c) and (d) are 5.39 and 5.82 kcal mol1, respectively.

Fig. 5. FTIR, FT-Raman and theoretical spectra of cis-2-methoxycinnamic acid.

respectively. In this molecule the dihedral angle (O19AC18AC17AC16; 0°) confirmed the s-cis configuration of the carboxylic carbonyl (C@O) and the side chain double bond (C16@C17). Similarly the dihedral angle (C18AC17AC16AC1; 0°) shows the cis-orientation of the carboxylic carbonyl and the aromatic ring with respect to the linear chain double bond (C16@C17). All these facts are evidences for the planar geometry of the compound. This may be explained by the strong stabilisation due to p-electron delocalisation, which is considerably more effective for a linear zig–zag like unsaturated chain, coplanar with the aromatic ring. There are four possible conformers for cis-2MCA. In cis-2MCA the s-cis orientation (a) of the carbonyl group (C@O) and the C@C bond appears as the only stable structure, lying about 2.43 kcal mol1 below the corresponding s-trans configuration (b). In the most stable conformer (a) the dihedral angle O19AC18AC17AC16 is found to be 180°. In the stable structure (a), the ACH@CHACOOH group is planar with respect to the phenyl ring. The dihedral angle O19AC18AC17AC16 with 0° give the structure (b) and is 2.43 kcal mol1 less stable than the stable

Structural properties Initially the conformational analysis of the compound has been carried out and predicted the stable structure with B3LYP/6-31G⁄⁄ method. Then the geometry has been optimised with higher basis sets like 6-311++G⁄⁄ and cc-pVTZ to get more reliable data. The optimised structural parameters numbering the bond length and bond angle for the thermodynamically preferred geometry of cis2MCA determined by B3LYP/6-311++G⁄⁄ and B3LYP/cc-pVTZ methods are presented in Table 1. For correlation of the theoretical values with that of the experimental data, only B3LYP/cc-pVTZ method has been considered, because the energy of the molecule determined by this method is low and thus the geometry is considered to be more stable. The C16@C17 double bond distance of cis-2MCA (1.351 Å) is shorter than the aromatic carbon–carbon bonds (1.386–1.424 Å). The C1AC16 bond length of cis-2MCA (1.456 Å) is consistent with the average aromatic vinyl bond lengths [47]. In the aromatic ring, the C1AC2 (1.42 Å) and C1AC6 (1.40 Å) bond lengths of cis-2MCA is longer than the other bonds. This shows the path of delocalisation of the p-electrons and is due to the high electron withdrawing nature of C16@C17 double bond. The delocalisation of the p-electrons is also induced by the electron donating nature of

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V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136 Table 4 The experimental and calculated 1H and acid.

13

C isotropic chemical shifts (diso, ppm) with respect to TMS and isotropic magnetic shielding tensors (riso) of cis-2-methoxycinnamic

Assignment

riso (1H)

Cal. (diso)

Expt. (d)

Assignment

riso (13C)

Cal. (diso)

Expt. (d)

H9 H10 H11 H12 H13 H14 H15 H21 H22 H23

24.64 24.01 24.45 21.39 27.52 27.93 27.93 25.72 23.01 25.60

7.3289 7.9589 7.5189 10.5789 4.4489 4.0389 4.0389 6.2489 8.9589 6.3689

6.87 7.28 6.89 7.52 3.81 3.81 3.81 11.2 7.25 6.96

C1 C2 C3 C4 C5 C6 C8 C16 C17 C18

55.20 16.59 71.28 44.58 59.94 43.43 127.95 35.71 68.14 10.84

129.3321 167.9421 113.2521 139.9521 124.5921 141.1021 56.5821 148.8221 116.3921 173.6921

123.73 157.26 110.38 130.96 120.03 130.75 55.31 141.45 119.02 172.15

Fig. 7.

13

C NMR spectrum of cis-2-methoxycinnamic acid.

the methoxy group. The theoretical values of cis-2MCA is correlated with the experimental data of trans-cinnamic acid [48]. The regression analysis for the bond lengths of the optimised structure is carried out and the R2 value is same for both the basis sets indicating that these methods are equally reliable and precise. In the benzene ring, the internal carbon angles are more than 120°, where the electron donating substituents are attached and it is less than 120°, where the electron withdrawing groups present [49]. In the present investigation, the bond angle C1AC2AC3 (120°) while and C2AC1AC16 (117.4°) reveals that the electron donating and electron withdrawing nature of methoxy group and the C16@C17 double bond, respectively. The deviations in the bond angles and dihedral angles are due to the cis and trans configuration. The thermodynamic parameters of the compound total thermal energy, vibrational energy contribution to the total energy, the rotational constants and the dipole moment values obtained from B3LYP method with 6-311++G⁄⁄ and cc-pVTZ basis sets are presented in Table 2. The energy of the compound cis-2MCA determined by B3LYP/cc-pVTZ method are 612.9711 Hartrees. The total dipole moments of the molecule determined by B3LYP/ccpVTZ method are 3.12 D. Vibrational analysis The geometry of cis-2MCA molecule possesses Cs point group symmetry. The normal vibrations are active both in IR and Raman

Fig. 8. 1H NMR spectrum of cis-2-methoxycinnamic acid.

and are distributed as 43 in-plane vibrations of A0 species and 20 out of plane vibrations of A00 species. i.e. Cvib = 41A0 + 22A00 . A detailed vibrational analysis has been carried out and assignments of the observed fundamental bands have been proposed on the basis of peak positions, the relative intensities and the available literatures. To compensate the mechanical anharmonicity and to get better agreement between the computed and experimental frequencies scale factors for different types of fundamental vibrations are used [50]. In the present investigation, the linear scaling equation method has been used [51–57] that minimises the residual separating experimental and theoretically predicted vibrational frequencies. The scaling equation y = 1.002x  2.9293 and

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y = 0.9998x  1.9035 are used to produce the scaled wavenumbers of cis-2MCA with cc-pVTZ and 6-311++G⁄⁄ basis sets, respectively. The RMS deviation between the experimental and observed wavenumbers are 1.8 and 2.5 for cis-2MCA using B3LYP method with ccpVTZ and 6-311++G⁄⁄ basis sets, respectively. The determined regression coefficients for both the methods are equal to one. The calculated harmonic vibrational frequencies and the observed FTIR and FT-Raman frequencies for various modes of vibrations are presented in Table 3. The observed FTIR and FT-Raman spectra along with the theoretically simulated spectra of cis-2-methoxycinnamic acid are shown in Fig. 5. CAC vibrations The bands which indicate aromatic properties of benzene derivatives mainly occur within the range of 1640–1200 cm1. The actual positions of these modes are determined not so much by the nature of the substituents but by the form of substitution around the ring [58,59]. The medium to strong lines observed in the infrared spectrum of cis-2MCA at 1599, 1574, 1491, 1291 and 1246 cm1 are assigned to the CAC stretching vibrations. The FTIR modes observed at 730 and 577 cm1 are assigned to the CCC inplane bending vibrations. The CCC out of plane bending modes of cis-2MCA are attributed to the Raman frequencies observed at 306, 268, 223, 194 and 162 cm1 [60–62]. The bands in the 1634–1642 cm1 region are assigned to the m(C@C) vibration. In this compound, the C@C of acrylic acid group appears at 1639 cm1 in IR and 1648 cm1 in Raman spectra. All the other CAC fundamental modes are represented in Table 3.

Fig. 9. The total electron density mapped with electrostatic potential surface of cis2-methoxycinnamic acid.

CAH vibrations The aromatic organic compounds always have stretching vibrations in the region 3000–3100 cm1 which is the characteristic region for the ready identification of CAH stretching vibrations. These vibrations are not found to be affected due to the nature and position of the substituents. The FTIR band observed at 3123, 3076, 3059 and 3009 cm1 and Raman bands at 3080 and 3051 cm1 are assigned to CAH stretching vibrations of cis2MCA. The stretching frequencies of olefenic hydrogen present in the acrylic acid part of cis-2MCA is found in the IR spectrum at 3044 and 3029 cm1. The @CAH in-plane bending modes are observed at 1377 and 1312 cm1, whereas the @CAH out of plane bending vibrations are assigned to 1023 and 837 cm1. The aromatic CAH in-plane bending modes of benzene and its derivatives are observed in the region 1300–1000 cm1. The peaks seen at 1107 and 946 cm1 in IR and the modes at 1063, 1012 and 967 cm1 in Raman are the corresponding aromatic CAH in-plane bending vibrations of cis-2MCA. The CAH out of plane bending mode of benzene derivatives are observed in the region 1100– 600 cm1. The aromatic CAH out of plane bending vibrations of cis-2MCA are seen in the infrared spectrum at 859, 752 and 682 cm1. The corresponding frequencies of cis-2MCA in Raman spectrum are observed at 851, 783, 757 and 687 cm1.

Fig. 10. The contour map of electrostatic potential of cis-2-methoxycinnamic acid.

Methoxy group vibrations The OCH3 group frequencies make a significant contribution to cis-2MCA. The asymmetric stretching and asymmetric deformation modes of the CH3 group would be expected to be depolarised for A00 symmetry species. The ms(CH3) frequency of cis-2MCA are established at 2876 cm1 in the infrared and 2889 cm1 in Raman, respectively and ma(CH3) are assigned at 2971 and 2940 cm1 in the IR and 2950 cm1 in Raman spectra. These assignments are substantiated by the reported literatures [63,64]. The in-plane methyl hydrogen deformation modes are also well established.

Fig. 11. The electrostatic potential surface of cis-2-methoxycinnamic acid.

V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136

131

Fig. 12. Frontier molecular orbitals of cis-2-methoxycinnamic acid.

Table 5 The calculated molecular orbital energies and global reactivity properties of cis-2methoxycinnamic acid (cis-2MCA) by B3LYP/cc-pVTZ method. Thermodynamic parameters (298 K)

cis-2-Methoxycinnamic acid B3LYP/cc-pVTZ

ELUMO+1 (eV) ELUMO (eV) EHOMO (eV) EHOMO1 (eV) ELUMO  EHOMO (eV) Ionisation potential, I (eV) Electron affinity, A (eV) Electronegativity (v) Chemical potential (l) Electrophilicity (x) Hardness (g) Softness (S)

0.1060 2.0196 6.2287 6.8342 4.2091 7.9548 0.3064 4.1306 4.1306 3.8242 2.2307 0.1308

The asymmetrical methyl deformational mode of cis-2MCA is obtained at 1455 cm1 in IR spectrum. The symmetrical methyl deformation mode of cis-2MCA is found at 1433 cm1 in IR. The methyl wagging mode of cis-2MCA is obtained at 1151 cm1 in FTIR spectrum. The vibrational assignments of the fundamental modes are also supported by GaussView molecular visualisation program [42]. Carboxylic acid (ACOOH) group vibrations In the molecule of cinnamic acid the carboxylic group is separated from the aromatic ring by a double bond. It causes

conjugation between the AC@CA bond and the p-electron system. Unassociated hydroxyl groups absorbs strongly in the region 3670–3580 cm1. The band due to the free hydroxyl group is sharp and its intensity increases. The stretching mode of hydroxyl group for cis-2MCA compound is appearing at 3433 cm1. Another strong band appears around 1700 cm1 (1700–1680 cm1 for aromatic acids) due to C@O stretching. The C@O and the CAO stretching frequencies (or the CAO stretching coupled with the OH in-plane bending vibration) reflecting a difference in the strength of the hydrogen bond. The cis-acid shows higher C@O and lower CAO frequencies than the trans acid. For the cis- acid also, the average value of the C@O doublet is slightly higher than the frequency of the trans- acid. The trans-cinnamic acid dimer formed by hydrogen bonding is nearly planar as a whole in the crystal [65–67], whereas the cis-acids are not [68,69]. The C@O and C@C stretching vibrations are normally found in the region 1800–1600 cm1. The C@O stretching frequency of cis-2MCA is ascribed to a frequency 1698 cm1. The C@O stretching mode is the strongest band in the infrared spectrum and appears with diminished intensity in the Raman spectrum. This is opposite to that observed in acrylic acid [70]. This is due to the presence of more delocalisation of the p-electrons towards the ring. Hence the very strong IR band observed at 1698 cm1 is assigned to the C@O band of cis-2MCA molecule. The CAO stretching frequency of cis-2MCA is attributed to 1129 cm1 in Raman spectrum. The CAO in-plane bending of cis2MCA molecule is observed at 538 and 549 cm1 in infrared and Raman spectrum. The in-plane OAH bending vibration give rise to the strong band in infrared spectrum of cis-2MCA at 1263 cm1 in IR and 1261 cm1 in Raman spectra, respectively.

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Table 6 Bond orbital analysis of cis-2-methoxycinnamic acid by B3LYP/cc-pVTZ method. Bond orbital

Occupancy

Atom

Contribution from parent NBO (%)

Atomic hybrid contributions (%)

C1A C2

1.9691

C1 C2

50.12 49.88

s(31.90) + p2.13(67.97) s(36.59) + p1.73(63.36)

C1AC6

1.9742

C1 C6

51.61 48.39

s(35.35) + p1.83(64.58) s(34.69) + p1.88(65.22)

C1AC6

1.6249

C1 C6

56.05 43.95

s(0.00) + p1.00(99.96) s(0.00) + p1.00(99.94)

C1AC16

1.9777

C1 C16

50.87 49.13

s(32.72) + p2.05(67.23) s(35.67) + p1.80(64.27)

C2AC3

1.9818

C2 C3

50.15 49.85

s(37.80) + p1.64(62.14) s(34.80) + p1.87(65.07)

C2AC3

1.6636

C2 C3

44.92 55.08

s(0.00) + p1.00(99.95) s(0.00) + p1.00(99.95)

C2AO7

1.9894

C2 O7

32.82 67.18

s(25.58) + p2.90(74.28) s(33.36) + p2.00(66.56)

C3AC4

1.9777

C3 C4

50.78 49.22

s(36.68) + p1.72(63.22) s(35.72) + p1.80(64.17)

C4AC5

1.9824

C4 C5

50.27 49.73

s(36.39) + p1.75(63.51) s(35.63) + p1.80(64.27)

C4AC5

1.6546

C4 C5

47.38 52.62

s(0.00) + p1.00(99.95) s(0.00) + p1.00(99.95)

C5AC6

1.9805

C5 C6

49.98 50.02

s(36.00) + p s(36.00) + p

1.77 1.77

(63.90) (63.90)

O7AC8

1.9911

O7 C8

67.61 32.39

s(28.08) + p2.56(71.82) s(23.22) + p3.30(76.63)

C16AC17

1.9859

C16 C17

50.05 49.95

s(39.32) + p1.54(60.57) s(40.62) + p1.46(59.31)

C16AC17

1.8533

C16 C17

44.61 55.39

s(0.00) + p1.00(99.94) s(0.00) + p1.00(99.95)

C17AC18

1.9828

C17 C18

50.58 49.42

s(32.00) + p2.12(67.90) s(38.61) + p1.59(61.31)

C18AO19

1.9967

C18 O19

35.61 64.39

s(34.60) + p1.89(65.34) s(39.17) + p1.54 (60.20)

C18AO19

1.9839

C18 O19

28.79 71.21

s(0.00) + p1.00(99.83) s(0.00) + p1.00 (99.64)

C18AO20

1.9946

C18 O20

32.42 67.58

s(26.80) + p2.73(73.04) s(31.36) + p2.18(68.51)

O20AH21

1.9877

O20 H21

74.50 25.50

s(21.77) + p3.59(78.13) s(99.85) + p0.00(0.15)

The correlation of the experimental and theoretical scaled wavenumbers of cis-2-methoxycinnamic acid are presented in Fig. 6.

NMR spectral studies The gauge independent atomic orbital (GIAO) [43,71] method is one of the most common approaches for calculating isotropic nuclear magnetic shielding tensors. The 13C and 1H NMR chemical shifts calculations of the title compound have been carried out with using B3LYP functional with cc-pVTZ basis set. The 1H and 13 C theoretical and experimental chemical shifts [72], isotropic shielding constants and the assignments of cis-2MCA are presented in Table 4. The observed 1H and 13C NMR spectra of the compounds cis-2MCA in CDCl3 solvent is given in the Figs. 7 and 8. The external magnetic field experienced by the carbon nuclei is affected by the electro negativity of the atoms attached to them. The effect of this is that the chemical shift of the carbon increases if the carbon is attached an atom like oxygen to it. Unsaturated carbons give signals in overlapped areas of the spectrum with chemical shift values from 100 to 200 ppm [73].

The C2 of cis-2MCA appears at about 157.26 ppm whilst the calculated chemical shift is 167.94 ppm. In cis-2MCA compound, the carbon atoms C1, C2, C3, C4, C5, and C6 are observed significantly with the chemical shift values 123.73, 157.26, 110.38, 130.96, 120.03 and 130.75 ppm, respectively. Comparing the chemical shift positions of ring carbon atom with that of methyl carbon atom (C8), the upfield chemical shift (55.31 ppm) of C8 is due to the hyperconjugative effect of methyl group. The 1H chemical shifts of cis-2MCA is obtained by complete analysis of their NMR spectra and interpreted critically in an attempt to quantify the possible different effects acting on the shielding constant and in turn to the chemical shift of protons. The hyperconjugative effect of methyl group is most pronounced on the chemical shifts of the benzene ring protons. The methoxy hydrogens are attributed to the upfield signals observed at 3.88 ppm, respectively shows that these protons are under high magnetic shielding. For cis-2MCA, the hydrogen atoms H9, H10 and H11 present in the benzene ring shows peaks at 6.87, 7.28 and 6.89 ppm, respectively. The methoxy protons are put into the upfield at 3.81 ppm, respectively. The calculated and experimental chemical shift values are given in Table 4 shows very good agreement with each other.

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V. Arjunan et al. / Journal of Molecular Structure 1080 (2015) 122–136 Table 7 Second order perturbation theory analysis of Fock matrix of cis-2-methoxycinnamic acid using NBO analysis. Donor (i)–acceptor (j) interaction

E(2)a (kJ mol1)

E(j)–E(i)b (a.u.)

F(i, j)c (a.u.)

r(C1AC2) ? r⁄(O7AC8) p(C1AC6) ? p⁄(C4AC5) p(C1AC6) ? p⁄(C16AC17) p(C2AC3) ? p⁄(C1AC6) p(C2AC3) ? p⁄(C4AC5) r(C3A C4) ? r⁄(C2AO7) r(C3A H9) ? r⁄(C1AC2) r(C3A H9) ? r⁄(C4AC5) p(C4AC5) ? p⁄(C1AC6) p(C4AC5) ? p⁄(C2AC3) r(C4A H10) ? r⁄(C2AC3) r(C4A H10) ? r⁄(C5AC6) r(C5A H11) ? r⁄(C1AC6) r(C5A H11) ? r⁄(C3AC4) r(C6A H12) ? r⁄(C1AC2) r(C6A H12) ? r⁄(C4AC5) r(C16A C17) ? r⁄(C1AC16) p(C16AC17) ? p⁄(C1AC6) p(C16AC17) ? p⁄(C18AO19) r(C16A H22) ? r⁄(C1AC6) r(C17A H23) ? r⁄(C1AC16) r(C17A H23) ? r⁄(C18AO19) r(C18A O19) ? p⁄(C16AC17) r(O20A H21) ? r⁄(C17AC18) n(LP(1)O7) ? r⁄(C2AC3) n(LP(2)O7) ? p⁄(C2AC3) n(LP(2)O7) ? r⁄(C8AH14) n(LP(2)O7) ? r⁄(C8AH15) n(LP(2)O19) ? r⁄(C17AC18) n(LP(2)O19) ? r⁄(C18AO20) n(LP(1)O20) ? r⁄(C18AO19) n(LP(2)O20) ? r⁄(C18AO19)

4.00 17.18 18.41 14.07 23.12 4.92 5.15 4.33 24.37 17.28 5.16 4.37 5.11 4.69 5.14 4.38 2.56 9.33 22.32 5.88 8.90 5.07 3.80 4.50 7.75 31.36 5.72 5.72 18.54 32.71 6.17 43.62

0.95 0.27 0.28 0.30 0.29 1.06 1.03 1.08 0.28 0.27 1.05 1.08 1.05 1.05 1.00 1.05 1.21 0.31 0.28 1.04 0.97 1.11 0.42 1.17 1.10 0.34 0.68 0.68 0.69 0.62 1.24 0.34

0.055 0.062 0.068 0.058 0.074 0.065 0.065 0.061 0.075 0.061 0.066 0.061 0.065 0.063 0.064 0.061 0.050 0.051 0.073 0.070 0.083 0.067 0.037 0.066 0.083 0.098 0.058 0.058 0.130 0.128 0.078 0.111

LP – lone pair. a Stabilisation (delocalisation) energy. b Energy difference between i(donor) and j(acceptor) NBO orbitals. c Fock matrix element i and j NBO orbitals.

Table 8 Atomic charges of cis-2-methoxycinnamic acid by NBO analysis using B3LYP/cc-pVTZ method. cis-2-Methoxycinnamic acid Atom

Neutral

Anion

Cation

C1 C2 C3 C4 C5 C6 O7 C8 H9 H10 H11 H12 H13 H14 H15 C16 C17 C18 O19 O20 H21 H22 H23

0.1426 0.3495 0.3058 0.1529 0.2304 0.1429 0.4993 0.2180 0.2093 0.2019 0.2058 0.2464 0.1896 0.1682 0.1682 0.0919 0.3235 0.7513 0.6132 0.6743 0.4804 0.2138 0.2104

0.1304 0.2996 0.3314 0.2858 0.2317 0.2285 0.5068 0.2094 0.1789 0.1685 0.1759 0.2395 0.1678 0.1529 0.1529 0.2486 0.4335 0.6914 0.7082 0.7202 0.4502 0.1823 0.1748

0.0173 0.4251 0.2836 0.0680 0.1031 0.1618 0.3911 0.2389 0.2409 0.2356 0.2372 0.2697 0.2200 0.1987 0.1987 0.1224 0.1400 0.7297 0.5586 0.6399 0.5009 0.2319 0.2359

Table 9 Reactivity descriptors–Fukui functions (fk) of cis-2-methoxycinnamic acid determined by B3LYP/cc-pVTZ method. Atom

cis-2-Methoxycinnamic acid þ

C1 C2 C3 C4 C5 C6 O7 C8 C16 C17 C18 O19 O20



fk

fk

fk

Df(k)

0.0121 0.0499 0.0257 0.1329 0.0014 0.0856 0.0075 0.0086 0.1567 0.1101 0.0600 0.0950 0.0459

0.1253 0.0755 0.0222 0.0850 0.1273 0.0189 0.1082 0.0209 0.0305 0.1835 0.0216 0.0547 0.0344

0.0566 0.0627 0.0239 0.1089 0.0643 0.0333 0.0578 0.0148 0.0631 0.1468 0.0192 0.0748 0.0402

0.1374 0.0256 0.0035 0.0479 0.1260 0.1045 0.1008 0.0123 0.1872 0.0734 0.0816 0.0403 0.0116

0

Analysis of molecular electrostatic potential Knowledge of the charge distributions can be used to determine how molecules interact with one another. One of the purposes of finding the electrostatic potential is to find the reactive sites of a molecule [74,75]. The molecular electrostatic potential surface (MEP) displays electrostatic potential (electron + nuclei) distribution, molecular shape, size and dipole moments of the molecule and it provides a visual method to understand the relative polarity of the compounds [76]. Electrostatic potential maps illustrate the charge distributions of molecules three dimensionally. The total electron density and MEP surfaces of the molecule are constructed by using B3LYP/cc-pVTZ method. The MEP mapped surface of the compounds and electrostatic potential contour map for positive and negative potentials are shown in Figs. 9–11. The colour scheme of MEP is the negative electrostatic potentials are shown in red, the intensity of which is proportional to the absolute value of the potential energy, and positive electrostatic potentials are shown in blue while Green indicates surface areas where the potentials are close to zero. Local negative electrostatic potentials (red) signal oxygen whereas local positive electrostatic potentials (blue) signal hydrogens in CAH and methyl group. Green areas cover parts of the molecule where electrostatic potentials are close to zero (CAC bonds). The MEP of cis-2MCA has the range +1.140e  102 to 1.140e  102. The total electron density of cis-2MCA lies in the range +5.033e  102 to 5.033e  102. More negative potentials (red) are found in the region of the electronegative oxygen atoms while positive potential (blue) is at the hydroxyl hydrogen. Analysis of frontier molecular orbitals The energies of HOMO, LUMO, LUMO+1 and HOMO1 and the energy gap LUMO–HOMO are calculated using B3LYP/cc-pVTZ method and the pictorial illustration of the frontier molecular orbitals and their respective positive and negative regions are shown in Fig. 12. The positive and negative phases are represented in red and green colour, respectively. The calculated energy gap LUMO– HOMO explains the ultimate charge transfer interface within the molecule. The hardness and softness of the molecule depends on the frontier molecular orbital energies. The LUMO–HOMO energy gap of cis-2MCA determined by B3LYP/cc-pVTZ method is 4.2091 eV. The frontier molecular orbital energies are presented in Table 5. The energies of the HOMO, LUMO, HOMO1 and LUMO+1 are 6.2287 eV, 2.0196 eV, 6.8342 eV and 0.1060 eV, respectively.

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Table 10 Reactivity descriptors–Fukui functions (sk) of cis-2-methoxycinnamic acid determined by B3LYP/cc-pVTZ method. Atom

cis-2-Methoxycinnamic acid

C1 C2 C3 C4 C5 C6 O7 C8 C16 C17 C18 O19 O20

sþ k

s k

s0k

Dsk

0.0016 0.0065 0.0034 0.0174 0.0002 0.0112 0.0010 0.0011 0.0205 0.0144 0.0078 0.0124 0.0060

0.0164 0.0099 0.0029 0.0111 0.0166 0.0025 0.0142 0.0027 0.0040 0.0240 0.0028 0.0071 0.0045

0.0074 0.0082 0.0031 0.0142 0.0084 0.0044 0.0076 0.0019 0.0083 0.0192 0.0025 0.0098 0.0052

0.0180 0.0034 0.0005 0.0063 0.0165 0.0137 0.0132 0.0016 0.0245 0.0096 0.0107 0.0053 0.0015

Table 11 Reactivity descriptors–Fukui functions (xk) of cis-2-methoxycinnamic acid determined by B3LYP/cc-pVTZ method. Atom

C1 C2 C3 C4 C5 C6 O7 C8 C16 C17 C18 O19 O20

cis-2-Methoxycinnamic acid

xþk

xk

x0k

Dx k

0.0271 0.1113 0.0572 0.2964 0.0030 0.1909 0.0166 0.0192 0.3496 0.2455 0.1338 0.2119 0.1025

0.2794 0.1685 0.0495 0.1896 0.2840 0.0422 0.2414 0.0467 0.0680 0.4093 0.0482 0.1220 0.0767

0.1262 0.1399 0.0534 0.2430 0.1435 0.0744 0.1290 0.0329 0.1408 0.3274 0.0428 0.1669 0.0896

0.3065 0.0572 0.0077 0.1068 0.2810 0.2331 0.2248 0.0275 0.4176 0.1637 0.1820 0.0899 0.0258

Natural bond orbital analysis Natural bond orbital analysis provides an efficient method for studying intra and intermolecular bonding and interaction among bonds, and also provides a convenient basis for investigating charge transfer or conjugative interactions present in the molecular systems [77]. Delocalisation of electron density between occupied Lewis-type (bond or lone pair) NBO orbitals and formally unoccupied (antibonding or Rydgberg) non-Lewis NBO orbitals correspond to a stabilising donor–acceptor interactions. Hyperconjugation may be given as a stabilising effect that arises from an overlap between an occupied orbital with another neighboring electron deficient orbital when these orbitals are properly oriented. The hyperconjugative interaction energy was deduced from the second-order perturbation approach of Fock Matrix in NBO basis between donor–acceptor orbitals [78]. The NBO method demonstrates the bonding concepts like atomic charge, Lewis structure, bond type, hybridisation, bond order, charge transfer and resonance possibility. Table 6 depicts the bonding concepts such as type of bond orbital, their occupancies, the natural atomic hybrids of which the NBO is composed, giving the percentage of the NBO on each hybrid, the atom label, and a hybrid label showing the hybrid orbital (spx) composition (the amount of s-character, p-character, etc.) of cis-2MCA determined by B3LYP/cc-pVTZ method. All donors orbitals are completely occupied with 2 electrons. The bonding orbital for C1C2 has 50.12% C1 character and 49.88% C2 character in a sp2 hybrid orbital. The bonding orbital for O7C8 has 61.61% O7 character and 32.39% C8 character in a sp3 hybrid orbital. The bonding orbital

Electrophilicity

Nucleophilicity

0.0969 0.6606 1.1559 1.5634 0.0106 4.5280 0.0689 0.4106 5.1377 0.5999 2.7773 1.7368 1.3363

10.3180 1.5137 0.8652 0.6396 94.3037 0.2208 14.5080 2.4354 0.1946 1.6668 0.3601 0.5758 0.7483

for C16AC17 has 50.05% C16 character and 49.95% C17 character in a sp2 hybrid orbital of the cis-2MCA compound. The bonding orbital of the carbonyl group C18AO19 has 35.61% C18 character and 64.39% O19 character in a sp2 hybrid orbital of cis-2MCA. The bonding orbital for C1AC16 posses 50.87% C1 character and 49.13% C16 character in a sp2 hybrid orbital. The CAC bonds of the benzene ring and C1AC16 of the side chain possess more p character than s character. This clearly indicates the delocalisation of p electrons among all the carbon atoms. The Fock matrix analysis yield different types of donor–acceptor interactions and their stabilisation energy. The donor–acceptor interactions having the stabilisation energy of more than 4 kcal mol1 determined by the second order perturbation theory of Fock matrix of cis-2MCA are presented in Table 7. In cis-2MCA molecule, the lone pair donor orbital, nO ? r⁄CO interaction between the oxygen lone pair and the C18AO19 antibonding orbital gives a strong stabilisation of 43.62 kcal mol1. The nO ? p⁄CC interaction between the lone pair of O17 and C2AC3 bond is stabilized by 31.36 kcal mol1. Among the pCC ? p⁄CC interactions, the bond pair donor orbital C4AC5 and the C1AC6 antibonding orbital give more stabilisation of 24.37 kcal mol1. Structure–activity descriptors The atomic charges of the neutral, cationic and anionic species of cis-2MCA calculated by natural population analysis using B3LYP/cc-pVTZ method is presented in Table 8. Significant changes in the atomic charges of ring carbon atoms were found for cis2MCA raised upon the electronic effects exerted by the methoxy group. Considering the atomic charges of the ring carbon atoms of cis-2MCA, the carbon atom C2 having more positive charge due to the high electronegativity of oxygen atom. All the other atoms in the ring have negative charges. The carbonyl carbon (C18) of the side chain has more positive and the oxygen (O19) has more negative charges because of the polarised carbonyl group. Both the carbon atoms of the C@C bond of the side chain contains negative charges. The small negative charge in C16 than C17 indicates the direction of delocalisation of the p-electrons of the C@C bond. The understanding of chemical reactivity and site selectivity of the molecular systems has been effectively handled by the conceptual density functional theory (DFT) [79]. Chemical potential, global hardness, global softness, electronegativity and electrophilicity are global reactivity descriptors, highly successful in predicting global chemical reactivity trends. The global parameters ionisation potential (I), electron affinity (A), electrophilicity (x), electronegativity (v), hardness (g), and softness (S) of the molecule are determined and displayed in Table 5.

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Fukui functions and local softness are extensively applied to probe the local reactivity and site selectivity. The formal definitions of all these descriptors and working equations for their computation have been described [80–82]. The Fukui functions of the individual atoms of the neutral, cationic and anionic species of cis-2MCA calculated by B3LYP/cc-pVTZ method are presented in Tables 9–11. The reactivity descriptor indicates that the molecule under investigation mainly gives nucleophilic substitution reactions except at C2. The local softness, relative electrophilicity ðsþ =s k Þ and relative k þ nucleophilicity ðs =s Þ indices, the dual local softness Dsk and the k k multiphilicity descriptors (Dxk) have also been determined to predict the reactive sites of the molecule and are summarised in Tables 9 and 11. The local reactivity descriptors of the individual a a a atoms of the molecule sak ¼ f k S; xak ¼ xf k and f k where, a = +,  and 0 represents local philicity quantities describing nucleophilic, electrophilic and free radical attack, respectively and presented in Tables 9–11 where the nature of activity of the individual atoms can be determined. Conclusions The most stable geometry of cis-2MCA compound under investigation is identified by DFT-B3LYP method with 6-311++G⁄⁄ and cc-pVTZ basis sets. Predicted vibrational frequencies were assigned and compared with the experimental wavenumbers and they agreed well with each other. NMR chemical shifts was calculated and compared with the experimental data. The molecular electrostatic potential of cis-2MCA has the range +1.140e  102 to 1.140e  102. The total electron density of cis-2MCA lies in the range +5.033e  102 to 5.033e  102. More negative potentials (red) are found in the region of the electronegative oxygen atoms while positive potential (blue) is at the hydroxyl hydrogen. The chemical reactivity and site selectivity of the molecule has been determined with the help of global and local reactivity descriptors. The reactivity descriptor indicates that the molecule under investigation mainly gives nucleophilic substitution reactions except at C2. The bonding orbital for C1AC16 with 1.9777 electrons has 50.87% C1 character and 49.13% C16 character in an sp2 hybrid orbital. Thus the present investigation provides geometrical parameters, kinetic and thermodynamic stability of the molecule, chemical hardness, the energy gap between the frontier molecular orbitals, the probable electronic transitions and chemical shifts of the compound. The structural parameters and normal mode of vibrations obtained from DFT methods are in good agreement with the experimental data. References [1] O.I. Aruoma, A. Murcia, J. Butler, B. Halliwell, J. Agric. Food Chem. 41 (1993) 1880–1885. [2] C.A. Rice-Evans, N.J. Miller, G. Paganga, Free Radic. Biol. Med. 20 (1996) 933– 956. [3] G. Cao, E. Sofic, R.L. Prior, Free Radic. Biol. Med. 22 (1997) 749–760. [4] V.L. Singleton, Am. J. Enol. 38 (1987) 69–77. [5] P. Groupy, A. Fleuriet, M.J. Amiot, J.J. Macheix, J. Agric. Food Chem. 39 (1991) 92–95. [6] M. Brenes-Balbuena, P. Garcia-Garcia, A. Garrido-Fernandez, J. Agric. Food Chem. 40 (1992) 1192–1196. [7] A. Serrano, C. Palacios, G. Roy, C. Cespon, M.L. Villar, M. Nocito, P. GonzalezPorque, Arch. Biochem. Biophys. 350 (1998) 49–54. [8] F.A.M. Silva, F. Borges, M.A. Ferreira, J. Agric. Food Chem. 49 (2001) 3936–3941. [9] H. Esterbauer, J. Gebicki, H. Puhl, G. Jurgens, Biol. Med. 13 (1992) 341–389. [10] B. Halliwell, J.C. Gutteridge, Free Radicals in Biology and Medicine, third ed., Oxford Science Publications, Oxford, U.K., 1999. [11] S. Passi, M. Picardo, M. Nazzaro-Porro, Biochem. J. 245 (1987) 537–542. [12] T. Nakayama, Cancer Res. 54 (Suppl) (1994) 1991s–1993s. [13] E. Sergediene, K. Jonsson, H. Szymusiak, B. Tyrakowska, I.M. Rietjens, N. Cenas, FEBS Lett. 462 (1999) 392–396. [14] M. Inoue, N. Sakaguchi, K. Isuzugawa, H. Tani, Y. Ogihara, Biol. Pharm. Bull. 23 (2000) 1153–1157.

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