Synthesis, characterization, spectral, thermal analysis and computational studies of thiamine complexes

Accepted Manuscript Synthesis, characterization, spectral, thermal analysis and computational studies of thiamine complexes Mamdouh S. Masoud, Doaa A. Ghareeb, Shahenda Sh. Ahmed PII:

S0022-2860(17)30129-1

DOI:

10.1016/j.molstruc.2017.01.086

Reference:

MOLSTR 23391

To appear in:

Journal of Molecular Structure

Received Date: 1 October 2016 Revised Date:

27 January 2017

Accepted Date: 30 January 2017

Please cite this article as: M.S. Masoud, D.A. Ghareeb, S.S. Ahmed, Synthesis, characterization, spectral, thermal analysis and computational studies of thiamine complexes, Journal of Molecular Structure (2017), doi: 10.1016/j.molstruc.2017.01.086. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Synthesis, characterization, spectral, thermal analysis and computational studies of thiamine complexes Mamdouh S. Masoud a, Doaa A. Ghareeb b, Shahenda Sh. Ahmed a a

RI PT

Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt E-Mail: [email protected], E-Mail: [email protected]. b Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt E-Mail: [email protected] __________________________________________________________________________________________________

SC

ABSTRACT

TE D

M AN U

Thiamine metal complexes were synthesized and characterized by elemental analysis, IR, electronic spectra, magnetic susceptibility, ESR spectra of Cu(II) complex and EDX for structural investigation of the complexes to know their geometries and mode of bonding. All the manganese, iron, copper, zinc, tungsten and mercury complexes are with octahedral geometry, while cobalt and nickel complexes are with tetrahedral geometry. The selenium and palladium complexes are with square planner geometry, while vanadium complex with stoichiometry (2:1) is with square pyramidal geometry. The thermal properties of the complexes were examined. The kinetic thermodynamic parameters were estimated from the TGA and DTA curves. Molecular modeling of the ligand and its complexes was performed using PC computer to give extra spot lights on the bonding properties of these compounds. Some theoretical studies were carried out to obtain the charges, bond lengths, bond angles and dihedral angles, energies of highest occupied molecular orbital (EHOMO), energies of lowest unoccupied molecular orbital (ELUMO), the separation energy (∆E), chemical potential, electronegativity, hardness, softness, ionization potential and electron affinity of the studied ligand and its complexes. Correlation analysis was done to explore the relationships between some different parameters of the studied complexes.

EP

Keywords: Thiamine, synthesis, complexes, spectral, thermal analysis, computational, correlation analysis. ____________________________________________________________________________________

INTRODUCTION

AC C

Thiamine hydrochloride, Figure (1), was the first water-soluble B-vitamin had been discovered (1). It was mainly known as "a neurine" due to preventing polyneuritis in animals(2). Thiamine and its derivatives are produced by micro-organisms in tiny amounts(3) and cannot be synthesized within tissues of animals(4) or by human body, so food and dietary supplements must be obtained. Thiamine hydrochloride is most stable at pH below 5, but at alkaline medium, it is unstable (3-4). While, in presence of an oxidant, like potassium ferricyanide, thiamine is converted into thiochrome form which is a highly fluorescent product(1,4) and can be used in determination of thiamine in foods and pharmaceutical preparations(1). The chemistry of interactions of thiamine with metal ions is very interesting due to the role of metal ions in the catalytic activity of thiamine and its derivatives in the biological reactions(5). It has a wide variety of coordination sites. It mainly requires a bivalent metal ion, such as Mg(II), Mn(II), Co(II), Cd(II), Zn(II), Hg(II), V(II), Pt(II), Pd(II) and Cr(II)(6) to improve its activity and catalytic function(7). It was suggested that the binding site is N1' atom in pyrimidine ring, Figure (1)(6).

1

ACCEPTED MANUSCRIPT

SC

RI PT

Masoud et al. reported the complexing properties and thermal behavior of biologically active compounds and their complexes and our research in this direction is continued (8-19). In the present work, a new series of metal thiamine complexes were synthesized using different metals of V, Mn, Fe, Co, Ni, Cu, Zn, Se, Pd, W and Hg. The main interest of this article is studying the spectral, computational studies and the thermal behavior of thiamine Cl HCl and its metal complexes. The mechanism of decomposition is explained and the thermodynamic parameters are evaluated and discussed.

M AN U

Figure (1): Thiamine Cl HCl structure.

EXPERIMENTAL Synthesis of thiamine metal complexes:

TE D

Metal thiamine complexes were prepared by mixing 1 mmol (0.337g) of thiamine hydrochloride dissolved in 10 ml of distilled water (ammonia solution was added to thiamine solution) with 10 ml of aqueous solution of 1 mmol of metal salts. In case of Fe(III) thiamine complex, the metal salt FeCl3.6H2O was added directly to thiamine solution without addition of ammonia solution. All complexes were heated at 70 ºC for about 20 min leading to precipitation. The complexes then cooled, collected and dried in oven at 60 ºC. The analytical data showed the formation of all complexes with stoichiometry 1:1, except vanadium complex with molar ratio (2:1). The analytical data and physical properties of ligand and its complexes are given in Table (1).

EP

Instruments and working procedures:

AC C

The metal contents were determined by atomic absorption spectrophotometer and complexometric titration with standard EDTA solution using suitable indicator as reported(20). C, H, N, and S contents of the complexes were analyzed using elemental analyzer. The chloride ion contents were analyzed by Volhard's method in acidic medium(21) using standard AgNO3. Infrared spectra of thiamine and its complexes were detected using potassium bromide disc on Perkin-Elmer spectrophotometer, Model1430 covering the range 350-4000 cm-1. It was calibrated by a polystyrene film (1602±1 cm-1). Electronic spectra of the colored complexes was detected covering the range 200-700 nm on Jasco (V-530) UV/Vis spectrophotometer. Hnmr spectra of the ligand was recorded in DMSO solvent with JEOL JNM ECA 500 MHz. X-band ESR spectra was recorded at frequency of 9.435 GHz with modulation amplitude 0.32. The g values were determined by comparison with 2,2-diphenyl picryl hydrazide (DPPH) signal (g=2.0037)(22). Energy dispersive X-ray (EDX) analysis was carried out under vacuum by the FEI Quanta 250 scanning electron microscope. Molar magnetic susceptibilities, corrected for diamagnetism using Pascal,s constants were determined at room temperature (298 K) using Faraday,s method. The measurements

2

ACCEPTED MANUSCRIPT

Table (1): Analytical data and physical properties of thiamine Cl HCl ligand and its complexes.

Color

Calculated (Found) %

Formula C C12H18N4OSCl2

[(VO)2O(th)(H2O)4]2H2O

Olive green

V2C12H29N4O8S

[Mn(th)Cl(H2O)3]3Cl.H2O

Pale orange

MnC12H25N4O5SCl4

[Fe(th)Cl3(H2O)2]2Cl.H2O

Brown

FeC12H24N4O4SCl5

[Co(th)Cl]2Cl.1.5H2O

Black

CoC12H19N4O2.5SCl3

[Ni(th)Cl2]2Cl.3H2O

Dark green

NiC12H23N4O4SCl4

[Cu(th)Cl2(H2O)2]Cl.H2O

Brown

CuC12H23N4O4SCl3

[Zn(th)Cl2(H2O)]Cl.H2O

Orange

ZnC12H20N4O3SCl3

Se(th)(H2O)2

Brown

[Pd(th)Cl]Cl.H2O

Dark brown

PdC12H18N4O2SCl2

[WO2(th)Cl(H2O)]Cl

Pale brown

WC12H19N4O4SCl2

[Hg(th)Cl2(H2O)]Cl

Dark green

HgC12H18N4O2SCl3

N

S

M

Cl

5.33

16.6

9.48

-

21.01

5.55 (5.07) 4.68 (4.82) 4.33 (4.27)

10.72 (9.95) 10.49 (10.33) 10.12 (10.34)

6.13 (5.78) 5.99 (6.26) 5.78 (5.49)

19.49 (21.03) 10.28 (10.53) 10.09 (10.68)

26.56 (26.10) 32.04 (31.56)

31.55 (31.39)

4.16 (4.41)

12.27 (12.50)

7.01 (6.98)

12.91 (12.74)

23.30 (23.56)

27.71 (27.32) 29.45 (30.07)

4.42 (4.71) 4.70 (3.96)

10.77 (10.39) 11.45 (12.55)

6.15 (6.44) 6.54 (6.81)

11.29 (11.82) 12.99 (11.38)

27.29 (26.96) 21.75 (22.21)

30.50 (30.11) 37.90 (38.23) 31.35 (31.21) 25.27 (25.02)

4.23 (3.96) 5.52 (5.73) 3.91 (3.73) 3.33 (3.46)

11.86 (12.13) 14.74 (13.85) 12.19 (13.10) 9.82 (9.52)

6.77 (6.88) 8.42 (8.20) 6.96 (5.83) 5.61 (5.44)

13.84 (14.03) 20.76 (21.82) 23.16 (24.65) 32.26 (32.97)

22.52 (23.23)

24.45 (25.01)

3.05 (3.01)

9.50 (9.14)

5.43 (5.21)

34.06 (34.00)

18.05 (19.10)

42.69 27.58 (26.89) 26.98 (26.57) 26.03 (26.43)

SC

White

H

EP

TE D

M AN U

Thiamine Cl HCl

RI PT

Ligand / Complex

AC C

SeC12H21N4O3S

3

-

15.43 (16.06) 12.44 (12.69)

ACCEPTED MANUSCRIPT

RI PT

were obtained using a Sherwood magnetic susceptibility balance, England. The instrument was calibrated with Hg[Co(SCN)4](23). Thermogravimetric analysis (TGA), Differential thermal analysis (DTA) and Differential scanning calorimetry (DSC) were measured for thiamine ligand and its complexes using the LINSEIS STA PT1000 in temperature range 25-600 ºC at 10 k/min, except for [Pd(th)Cl]Cl.H2O complex at different heating rates (5, 15 and 25 k/min). The analysis was performed under oxygen medium.

SC

The molecular modeling calculations of thiamine ligand and its complexes were performed with Chem Bio Office 3D Ultra 12.0 computer program software. Hyper chemistry software, version 8.0.7 was applied for the organic ligand and its complexes with numerical technique PM3 semi-empirical and Molecular Mechanics Force Field (MM+) methods for calculations of the theoretical Quantum Chemical Parameters (24). RESULTS AND DISCUSSION

M AN U

Infrared spectral studies of thiamine Cl HCl and its complexes:

The fundamental infrared bands of thiamine Cl HCl and its complexes are given in Table (2). Thiamine shows major bands assigned to OH, NH and CH (aromatic or aliphatic) stretching's(25-26), where, shifted upon complexation in the range 3423-3316 and 3159-3036 cm-1 except Fe(III) complex has no significant change. The shift in frequencies of OH stretching’s detected in metal complexes may be due to the very strong hydrogen bonds interactions(27).

TE D

Two bands due to coupling of δ(NH2) bending and ν(C=N) motions of pyrimidine ring stretching(28) indicating protonated N1 site, overlapped and shifted to lower frequencies (1646-1603 cm-1) on complexation except Fe(III) complex had no change. The assignment of ν(C=C) and ν(C=N) of pyrimidine ring increased in all metal complexes suggesting the coordination through the pyrimidine ring via (N1) position with the metal center(29) except for Fe(III) and Hg(II) complexes indicating their non involvement of (N1) site in the coordination.

AC C

EP

The assigned ν(C-OH) stretching involved in thiazole ring shifted for Co(II), Zn(II), Pd(II) and Hg(II) complexes, indicating involvement of (OH) group in complexation for these complexes. While, latter complexes showed nearly the same frequency for (C-OH) assignment, indicating the non-involvement of OH group in coordination(30). (C-S) stretching assignment showed sharp peak at 788 cm-1 (31) for thiamine ligand and disappeared for VO2+, Mn(II), Ni(II), Se(IV) and Hg(II) complexes while shifted for Co(II), Cu(II), Zn(II), Pd(II) and WO2 complexes in the range 840-801 cm-1 suggesting sharing of sulphur atom in coordination. For VO2+ complex a very strong band at 979 cm-1 that attributed to the vibrations of ν(V=O) cation(31) indicating the presence of V(IV) ion in the oxo-cation form (V=O). Furthermore, the polymeric nature (bridging vanadyl group (–V-O-V-)) is supported by the presence of broad absorption band in the range 820-450 cm-1(32). For (WO2) complex a new band at 920 and 888 cm-1 is attributed to the presence of (WO2) group describing the antisymmetric and symmetric streching’s modes, respectively(33).

4

ACCEPTED MANUSCRIPT

Table (2): Fundamental infrared bands (cm-1) of thiamine Cl HCl and its complexes.

[Fe(th)Cl3(H2O)2]2Cl.H2O

νC-N

3491, 3424 3190, 3048 2961, 2909

1663, 1613

1530 1480

1424 1380

1186

1045

788 751

---

---

---

3423.5

1653

1542

1400

1218

1044

---

510 H2O

---

---

3376 3146, 3040 3491,3359,3316 3163, 3062 2967, 2910

1648 1603

1554

1401

1041

769

510 H2O

475

390

1662 1606

1539. 1477

3145.3

1651

[Ni(th)Cl2]2Cl.3H2O

3329.4 3181.4

1649

[Cu(th)Cl2(H2O)2]Cl.H2O

3136.26, 3036

1652

[Zn(th)Cl2(H2O)]Cl.H2O

3132, 3038

1653

3363.7

1646 1621

3159.7, 3045

1646

[Se(th)(H2O)2] [Pd(th)Cl]Cl.H2O [WO2(th)Cl(H2O)]Cl

3405 3180

[Hg(th)Cl2(H2O)]Cl

3393 3208

1543 1515 1542 1518 1547

1542 1518 1542 1516

1546

AC C

[Co(th)Cl]2Cl.1.5H2O

ν(C-OH)

ν(C-S)

ν(M-O) ν(M-N)

ν(M-S)

RI PT

---

1428.8 1382.5

1190

1042

805,792 768

513.6 H2O

451.35

384.7

1401.6

---

1081

808 768

513

420

393.8

1400.3

---

1041

769

---

418

393

1404

1126

1043

490 H2O

410

385.87

1400.36

---

1037

801 764 805 770

504.5

420

366.7

1458.4 1423.99

---

1045

774

517 H2O

418

394 373

1402.7

---

1036

805 763

524

425

395

1648 1598

1560

1434

---

1045

840 800

490 H2O

429

390

1651

1538 1518

1452.2 1400.6

---

1024

770

518

410

390

5

Other assign.

Str

SC

[Mn(th)Cl(H2O)3]3Cl.H2O

ν(C=C, C=N) (thiaz.) ring

M AN U

[(VO)2O(th)(H2O)4]2H2O

Skeletal ν(C=C,C=N) (Py.) ring

TE D

Thiamine Cl HCl

ν(C=N) +NH2 bend.

EP

Ligand/Complex

ν(OH),ν(NH), ν(CH)

4128-3673 H2 O 469Cl3835-3745 H2 O 979 V=O 3840-3750 H2 O 4312-3738 H2 O 3835-3673 H2 O 3835-3746 H2 O 3924-3671 H2 O 3804-3672 H2 O 3836-3747 H2 O 3861-3648 H2 O 3856-3727 H2 O 889 W=O 3834-3741 H2 O

ACCEPTED MANUSCRIPT

Broad bands in the range 3400-3590 cm-1 assigned to crystallized or coordinated water molecules(34) in all complexes. However, coordinated water in these complexes is indicated by the appearance of metaloxygen bands attributable to rocking modes at 490-517 cm-1(35), observed for Cu(II), Mn(II), Fe(III), VO2+, Se(IV) and WO2 complexes.

Electronic Spectra and magnetic susceptibility (µeff) studies:

RI PT

Bonding of nitrogen, sulphur and oxygen atoms to metal is confirmed by assignments of ν(M-O) in range 504-524cm-1 for Zn(II), Co(II), Pd(II) and Hg(II) complexes. While, ν(M-N) in the range 410-451 cm-1(36) in Zn(II), Fe(III), Co(II), Ni(II), Cu(II), Se(IV), Pd(II), (WO2) and Hg(II) complexes. ν(M-S) assignment was observed in all complexes in the range 366-393.8 cm-1(37).

SC

The green VO2+ complex, showed only one broad band at 296 nm due to intense charge transfer transition (2B2g → 2A1g ) from the ligand to the vanadium center, suggesting a square pyramidal geometry and confirmed by the magnetic moment value 1.6 B.M. close to the spin only value 1.73 B.M..

M AN U

The light orange [Mn(th)Cl(H2O)3]Cl3.H2O, showed two weak bands at 271 and 324 nm attributed to (π → π*) transition of pyrimidine ring of thiamine and charge transfer (CT) from ligand to Mn(II). The magnetic moment of Mn(II) complex is 5.6 B.M near to the spin only value 5.96 B.M. confirming the octahedral geometry(38). The brown [Fe(th)Cl3(H2O)2]2Cl.H2O, showed two bands at 290 and 340 nm assigned to π →π* electronic transitions of heteroaromatic moiety in thiamine and CT (t2g→π*)(16). The magnetic moment is 4.33 B.M. that suggests the existence of octahedral geometry with a high spin state(39).

TE D

The black Co(II) complex, showed four bands at 283, 340, 361 and weak one at 520 nm. These are due to the charge transfer and three spin-allowed electronic transitions to the excited quartet states, 4A2(F)→ 4 T2(F), 4A2(F) → 4T1(F) and 4A2(F)→4T1(P) transitions, respectively, suggesting a tetrahedral Co(II) complex(29) confirmed by magnetic moment of 4.62 B.M. which lie in the range of tetrahedral stereochemistry (4.1-4.8 B.M.).

AC C

EP

The black green nickel (II) complex, showed four bands at 286, 321, 371 nm and weak one at 529 nm due to charge transfer and the three spin-allowed electronic transitions to the excited triplet states, 3 A2→3T2(F), 3A2→3T1(F) and 3A2→3T1(P)(40), respectively, which suggest the tetrahedral complex confirmed by µeff = 3.46 B.M.. The brown [Cu(th)Cl2.(H2O)2]Cl.H2O, showed only one absorption band due to Jahn-Teller effect at 282 nm assigned to π→π* transition with a distorted octahedral geometry(41). The magnetic moment gave a subnormal magnetic moment 1.36 B.M. indicative for some extended interaction in the complex(42). The brown [Se(th)(H2O)2], exhibited two bands at 262 and 369 nm, assigned to π → π* and charge transfer from metal to ligand transitions MLCT(43), indicating that thiamine ligand is binding to selenium metal through the lone pair of electrons suggesting square planar geometry which typified by magnetic moment 0.92 B.M.. The pale brown [WO2(th)Cl(H2O)]Cl complex, showed two weak bands at 271 and 323 nm ascribing to the π→π* and LMCT charge transfer, indicating octahedral geometry, typified by magnetic moment 1.65 B.M. (low value due to spin orbit coupling). 6

ACCEPTED MANUSCRIPT

RI PT

The orange [Zn(th)Cl2(H2O)]Cl.H2O, showed very weak absorption due to no d-d transitions. The weak band is at 283 nm assigned to π→ π* transition suggesting the octahedral geometry. The dark green [Hg(th)Cl2(H2O)]Cl complex, showed two bands at 272 and 383 nm corresponding to the π→ π* transition and spin allowed ligand to metal charge transfer LMCT indicating the octahedral arrangement for Hg(II). The dark brown [Pd(th)Cl]Cl.H2O complex, showed two bands at 274 and 380 nm assigned to the intra-ligand π→ π* transition and spin allowed LMCT (1A2g) → (1A1g) indicating the square planar (D4h) geometry of the Pd(II) ion(44). The magnetic moment of [Pd(th)Cl]Cl.H2O complex is 1.02 B.M. indicating the low spin square planar geometry for the structure(45). The magnetic moments of [Zn(th)Cl2(H2O)]Cl.H2O and [Hg(th)Cl2(H2O)]Cl complexes give negative values that attributed to the diamagnetic behavior of these complexes confirming their octahedral geometry.

AC C

EP

TE D

M AN U

SC

IR, electronic absorption spectra and magnetic moment values concluded structures shown in Figure (2).

7

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

Figure (2): Proposed structures of thiamine complexes.

Nuclear magnetic resonance (NMR): Hnmr spectra of thiamine Cl HCl, Table (3). The data were recorded in DMSO, where the proton resonance at 9.05 and 9.25 ppm are attributed to C-2-H and C-4’-NH2, respectively. The signal due to C6'-H is observed at 8.40 ppm. The resonance at 5.60 ppm is assigned to C-5'-CH2, while the resonance at 3.71 ppm is assigned to CH2-OH. The signal of C(5)-CH2 is located at 3.53 ppm. The resonance at 2.86 and 2.49 ppm attributable to C(4)-CH3 and C(2’)-CH3, respectively. As a result, the observed proton resonances confirm the structure of thiamine ligand.

8

ACCEPTED MANUSCRIPT

Table (3): Hnmr of thiamine Cl HCl assignments and their signals in ppm. C(2')-CH3 2.49(t) C(4')-NH2 9.25

C(4)-CH3 2.86 C(2)-H 9.945

C(5)-CH2 3.5(t)

CH2-OH 3.71

C(5')-CH2 5.60

C(6')-H 8.40

RI PT

Assignments Signals (ppm)

Electron spin resonance (ESR):

SC

The X-band ESR spectrum of [Cu(th)Cl2(H2O)2]Cl.H2O complex, Figure (3), Table (4), gave two g values (gǁǁ= 2.26 and g┴=2.11) with Aǁǁ= 117G and A┴= 100G. The spectrum shows broad lines with a slight resolution of hyperfine structure, may support the Cu-N coordination(46).

M AN U

The g values of Cu(II) complex with a relation gǁǁ > g ┴ > ge (2.0023) suggesting that Cu(II) has a 2B1g (dx2-y2) ground state for the unpaired electrons assigning to axial-elongated distorted octahedral geometry(46). The gǁǁ > 2.3 suggests ionic character and gǁǁ < 2.3 suggests covalent character(37). gǁǁ=2.26 value for Cu(II) complex suggesting the covalent character. The mean g value is calculated from the equation(47): = 1/3(gǁǁ + 2g┴)

TE D

and equals =2.156. The deviation of from ge value also confirm the covalent character with distorted octahedral symmetry(48). The G value for Cu(II) complex is calculated from G = (gǁǁ - 2.003) / (g⊥ - 2.003) = 4.0 and equals 2.49 suggesting strong interaction between the active centers of the organic ligand and the metal ion centers in the solid state(45), which is further confirmed by its subnormal magnetic moments value(49). The F parameter calculated from F= (gǁǁ / Aǁǁ), describes the degree of distortion of coordination geometry . The present Cu(II) complex has (gǁǁ / Aǁǁ= 192.9), which lies in the range >135-270 cm-1 (50) reported for tetragonal distorted Cu(II) complexes. The covalency parameter can be calculated from A value by the following equation (16): (49)

EP

α²= Aǁǁ/0.036 + (gǁǁ - 2.0023) + 3/7(g┴-2.0023) + 0.04

AC C

From calculated data, α² = 0.664 lower than unity which afford the covalent character(51). The α² value predicts the bonding site of ligand oxygen or nitrogen, where the α2 value for tetragonal distortion ranges between 0.63-0.84 for nitrogen donor ligands (M-N bonding)(52). Hence, the calculated (α²= 0.664) of Cu(II) complex indicates that thiamine ligand acts as a nitrogen donor ligand for Cu(II) ion that is in agreement with the IR data for Cu(II) complex. Table (4): ESR parameters of [Cu(th)Cl2(H2O)2]Cl.H2O complex. G 2.49

F (gǁǁ/Aǁǁ) 192.9

α² 0.664

A┴ 10-4 100

Aǁǁ 10-4 117

2.156

9

g┴ 2.11

gǁǁ 2.26

Complex [Cu(th)Cl2.(H2O)2]Cl.H2O

RI PT

ACCEPTED MANUSCRIPT

SC

Figure (3): ESR spectrum of [Cu(th)Cl2(H2O)2]Cl.H2O complex. Energy dispersive X-ray (EDX) analysis :

M AN U

EDX spectrum of [Hg(th)Cl2(H2O)]Cl complex indicates the presence of C, N, S, O, Cl and Hg with a specific energy at 2.3 KeV, while [Cu(th)Cl2(H2O)2]Cl.H2O complex contains C, N, S, O, Cl and Cu with energy at 8 KeV also the spectrum of [Pd(th)Cl]Cl.H2O complex involves C, N, S, O, Cl and Pd with energy at 2.85 KeV. The spectrum of [(VO)2(th)(H2O)4]2H2O complex indicates the presence of C, N, S, O and V with energy at 5 KeV, also [Se(th)(H2O)2] complex contains C, N, S, O and Se with energy at 1.5 KeV. Thermal analysis:

TE D

TGA, DTA and DSC analysis was discussed for thiamine Cl HCl ligand and selected six complexes, [(VO)2O(th)(H2O)4]2H2O, [Fe(th)Cl3(H2O)2]2Cl.H2O, [Co(th)Cl]2Cl.1.5H2O, [Cu(th)Cl2(H2O)2]Cl.H2O, [Zn(th)Cl2(H2O)]Cl. H2O and [Pd(th)Cl]Cl.H2O. a) Thermogravimetric analysis (TGA) data:

AC C

EP

The thermogravimetric curve for thiamine Cl HCl showed four well separated decomposition steps within the range 23-500 ᵒC, Table (5). It shows high thermal stability until 210 ºC, which is in a harmony with a reported study(53). The first step at 23.1-163.6 ᵒC is attributed to dehydration of a hemihydrate molecule with mass loss 2.14% (2.59%) and activation energy 32.58 KJ/mol. It decomposes rapidly in the second step around 220-268.7 ºC with a mass loss of 37.13% (38.08%) due to removal of Cl, HCl, CH3 and C2H4OH with highest activation energy 82.10 KJ/mol. The significant thermal degradation with a cleavage of C-N bond of the bridged methylene between thiazole and pyrimidine moieties, leading to two major products of thiazole and derived pyrimidine ring(54). The third step shows partial decomposition of thiazole yielding hydrogen sulfide (H2S) and CH=NH. The fourth step shows further removal of the latter carbonaceous species. However, 0.5 NH2 and pyrimidine derivative remained as a residue with mass of 32.67% (32.91%). TGA thermogram of the square pyramidal [(VO)2O(th)(H2O)4]2H2O complex, Figure (4), showed five degradation steps within the range 35.3-700 ºC, Table (5). The first TG peak in the range of 35.3-95.7 ºC is attributed to removal of two crystallized water molecules and one coordinated water molecule with mass loss 11.33% (10.34%) and activation energy 41.16 KJ/mol. The second step in the range of 95.8157.9 ºC is attributed to 2.5 coordinated water molecules with mass loss 8.90% (8.61%) and activation

10

ACCEPTED MANUSCRIPT

energy 8.39 KJ/mol. The rest steps are due to decomposition of the complex ended with the formation of V2O3 as a final product with percent 27.14% (28.60%). The mechanism of decomposition is represented in scheme (1).

RI PT

TGA thermogram of [Fe(th)Cl3(H2O)2]2Cl.H2O showed well defined five thermal decomposition steps in the range 22.8-499.1 ºC, Table (5). The first two successive steps attributed to removal of the crystallized water and coordinated water molecules with mass loss of 1.68% (1.63%) and 6.07% (6.50%) and activation energies 59.06 and 17.28 JK/mol, respectively. The remaining steps are due to further decomposition with formation of Fe metal and the rest of the ligand as a residue with percent 40.92% (41.01%).

SC

TGA thermogram of the tetrahedral [Co(th)Cl]2Cl.1.5H2O complex showed three decomposition steps in the range 46.6-496.9 ºC, Table (5). The first step is attributed to the dehydration of 1.5 lattice water with mass loss 6.19% (5.9%) and activation energy 34.16 KJ/mol. Remaining steps are due to decomposition of complex ended with a final product of rest of ligand + Co metal with mass percent 63.22% (63.56%).

M AN U

TGA thermogram of the octahedral [Cu(th)Cl2(H2O)2]Cl.H2O complex showed five decomposition steps in the range 35.1-599.1 ºC, Table (5). The first step is associated with loss of 1.5 crystallized water in temperature range 35.1-131 ºC with mass loss 5.1% (5.52%) and activation energy 12.37 KJ/mol. Second step is attributed to further removal of remained crystallized and coordinated water molecules. Remaining steps are attributed to further decomposition of complex yielding a residue Py-CH2 + Cu metal with mass percent 30.46% (31.39%).

TE D

TGA thermogram of the octahedral [Zn(th)Cl2(H2O)]Cl.H2O complex showed three decomposition steps in the temperature range 31.8-496.6 ºC, Table (5). The first one is attributed to dehydration of one crystallized water molecule and one coordinated one with mass loss 6.83% (7.62%) and activation energy 17.53 KJ/mol, while second and third one involved decomposition of complex ended with formation of (Py-CH2+C=N-C=C+C2H4 + ZnO) as a final product with mass percent 53.3% (53.45%).

EP

TGA thermogram of the square planar [Pd(th)Cl]Cl.H2O complex at (5 K/min) heating rate showed three decomposition steps in the range 38.3-461.3ºC, Table (5). The first step is attributed to the dehydration of one lattice water molecule with mass loss 2.5% (3.9%) and activation energy 11.74 KJ/mol. Second and third steps are due to decomposition of the complex ended with a formation of metal oxide (PdO) as a residue with mass percent 28.30% (26.64%).

AC C

TGA thermogram of the square planar [Pd(th)Cl]Cl.H2O complex at (15 K/min) heating rate showed three decomposition steps in the range 32.7-494.8ºC, Table (5). The first step is attributed to dehydration of one lattice water molecule and 0.5 Cl with mass loss 8.75% (7.77%) and activation energy 9.89 KJ/mol. Remaining steps are due to decomposition of the complex ended with a residue 0.5 PdO with mass percent 12.18% (13.31%). TGA thermogram of [Pd(th)Cl]Cl.H2O complex at (25 K/min) heating rate showed three decomposition steps in the range 35-499.1ºC, Table (5). The first step is attributed to dehydration of one lattice water molecule and Cl with mass loss 11.23% (11.62%) and activation energy 11.80 KJ/mol. Second and third steps are due to decomposition of the complex ended with a residue 0.5 PdO with mass percent 12.17% (13.31%) is remained.

11

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

Scheme (1): Proposed thermal degradation pathway of [(VO)2O(th)(H2O)4]2H2O. Thermodynamic and kinetic studies: The kinetic parameters, activation energies (Ea) of such a decomposition step and Pre-exponential factor (A) can be determined from TGA thermogram by Coats-Redfern method(55) as follows: ln [g(α)/T2] = ln (AR/βE) - Ea/RT

α is the fraction of decomposed substance at time t, T is the TGA temperature peak and β is the heating rate. The correlation coefficient, R2, can be calculated using the least square method by plotting ln [g(α)/T2] against 1/T for the selected metal complexes, where Ea can be obtained from the slope and A from the intercept(53). The data obtained are given in Table (5).

12

ACCEPTED MANUSCRIPT

From TGA data, Table (5), it was concluded that: -The activation energy, Ea, increases clearly for the successive degradation steps revealing a high stability of the remaining part of the chelate. The highest values suggesting a high stability may be due to their covalent bond character(56).

RI PT

-The value of (A) parameter lies in the range 9.47x10-8-1.46x103 indicating a direct proportional relation to Ea. b) The differential thermal analysis:

The DTA data of thiamine Cl HCl ligand and its complexes are given in Table (6).

M AN U

SC

DTA curve of thiamine Cl HCl ligand showed two endothermic peaks at 221 ºC and 432.9 ºC with activation energies 37.32 and 73.13 KJ/mol and reaction orders 0.84, and 0.55, respectively, i.e orders are of the first order. The first peak represents the dehydration step. DTA data of thiamine chloride gives an indication for its stability until 200 ºC which is in agreement with the TGA data. DTA curve of [(VO)2O(th)(H2O)4]2H2O complex gives three peaks, Figure (4). The first one is endothermic attributed to the dehydration of crystallized and coordinated water molecules and the third one is a broad sharp intense exothermic at 86.1 ºC and 521.1 ºC(36) with activation energies 134.52 and 217.57 KJ/mol and reaction orders 1.38 and 1.26, respectively. All the orders are of the first type. The second peak is very sharp exothermic peak at 340 ºC.

TE D

DTA curve of [Fe(th)Cl3(H2O)2]2Cl.H2O complex showed three endothermic peaks at 229.9 °C, 394.7 °C and 455 ºC with activation energies 113.07, 98.85 and 168.77 KJ/mol and reaction orders of 1.34, 0.95 and 0.63, respectively, which are of the first order. The first endothermic peak is attributed to dehydration of water molecules.

EP

DTA curve of [Co(th)Cl]2Cl.1.5H2O complex showed two significant peaks. The first one is endothermic and second one is exothermic at 108.7 ºC and 413.7 ºC with activation energies 31.31 and 103.34 KJ/mol and reaction orders 2.17 and 1.48, respectively. The reaction order of the first peak is of second type while second peak is of the first type.

AC C

DTA curve of [Cu(th)Cl2(H2O)2]Cl.H2O complex showed four peaks at 121.2, 341.4, 464.5 and 580 ºC. The first three peaks are endothermic with activation energies 26.23, 91.53 and 134.52 KJ/mol and reaction orders 1.76, 0.698 and 0.66, respectively. First peak is of second type, while second and third peaks are of first type. The fourth peak is very sharp exothermic peak. First peak is assigned to the dehydration of lattice and coordinated water molecules. DTA curve of [Zn(th)Cl2(H2O)]Cl.H2O complex showed two endothermic peaks one is major peak and second is very sharp peak at 214.9 ºC and 457 ºC, respectively. The first peak has activation energy 20.119 KJ/mol and reaction order 1.33 attributed to a first order reaction. DTA curve of [Pd(th)Cl]Cl.H2O complex at heating rate 5 K/min showed three peaks. The first one is endothermic while second and third ones are exothermic at 255, 310 and 404 ºC with activation energies 31.31, 77.23 and 288.08 KJ/mol and reaction orders 0.43, 2.46 and 1.14, respectively. The reaction order of the first and third peaks are of first type while second peak is of the second type. 13

ACCEPTED MANUSCRIPT

DTA curve of [Pd(th)Cl]Cl.H2O complex at heating rate 15 K/min showed three peaks. The first one is endothermic while second and third ones are exothermic at 283 ºC, 345 and 432.8 ºC with activation energies 33.92, 227.30 and 170.35 KJ/mol and reaction orders 2.31, 1.95 and 1.23, respectively. The reaction order of the first and second peaks are of second type while third peak is of the first type.

RI PT

DTA curve of [Pd(th)Cl]Cl.H2O complex at heating rate 25 K/min showed two peaks. The first one is endothermic while second one is exothermic at 282.4 ºC and 445.8 ºC with activation energies 11.51 and 200.11 KJ/mol and reaction orders 0.41 and 1.35, respectively. The reaction orders of both peaks are of the first type. The order of the thermal process (n) is determined from the peak symmetry method from DTA curve by kissinger(57). The peak asymmetry, S and reaction order (n) are determined from relations(10): n= 1.26 (a/b)1/2

SC

S=0.63 n2,

The collision factor, Z, can be measured in case of the Horowitz-Metzger by using this relation(58):

 E E φ exp  2 RT m  RT m

 kT m  ∆S #  =   exp  h R   

M AN U

z=

TE D

Ea is the activation energy, R is the molar gas constant (8.314 JK-1mol-1), β is the heating rate (KS-1), Tm is the peak temperature, k is the Boltzmann constant, h is the Planck's constant and ∆S# is the entropy of activation(10). The change of entropy, ∆S#, values for all complexes, Table (6), are nearly of the same magnitude and lie within the range (-0.22 to -0.25) k Jk-1mol–1 with negative values indicating spontaneous decomposition. So, the transition states are more ordered, i.e. in a less random molecular configuration than the reacting complex. The calculated values of the collision number, Z, showed a direct relation to Ea.

EP

The values of the decomposed substance fraction, αm, at the maximum development of the reaction with T = Tm can be calculated from the equation(10): (1- αm) = n1/(1-n)

AC C

It is of nearly the same magnitude and lies within the range (0.46-0.78). The change in enthalpy (∆H# in KJ/mol) occurs at any peak temperature Tm for any phase of transformation and determined from equation (10): ∆S#= ∆H# / Tm

∆H# values lied in the range -82.69 to -189.58 KJ/mol. According to the least square calculations, the ln ∆T is plotted against 103/T for each DTA curve for all complexes then straight lines are obtained, hence, the activation energies are determined according to Piloyan et al method(59). The slope is considered to be of Arrhenius type with value –Ea/R.

14

ACCEPTED MANUSCRIPT

Table (5): TGA kinetic parameters for thiamine ligand and its complexes.

[Fe(th)Cl3(H2O)2]2Cl.H2O

[Cu(th)Cl2(H2O)2]Cl.H2O

0.023 2.77x102

268.8 - 347

17.73

6.13x10-5

18.92 (17.90)

348 - 488.3

10.19

6.91x10-6

35.3-95.7 95.8-157.9 158-330.8 330.9-480.7 480.8-596.8

41.16 8.39 1.09 4.48 98.26

0.86 3.23x10-6 2.89x10-8 6.17x10-8 13.48

22.8 – 109.2 109.2 – 216.8 216.8 – 297.6 297.6 – 394.4 394.4 – 499.1

59.06 17.28 32.81 17.23 38.47

1.46x103 1.78x10-5 1.02x10-3 1.73x10-5 1.24x10-3

9.07 (10.39) 32.67 (32.91) 11.33 (10.34) 8.90 (8.61) 12.54 (13.21) 7.59 (6.51) 32.52 (32.93) 27.14 (28.60) 1.68 (1.63) 6.07 (6.50) 13.15 (14.44) 11.97 (10.84) 26.02 (25.37) 40.92 (41.01)

35.1 - 131

12.37

131 - 297.3 297.3 - 396.7 396.7 - 506.5

6.82 29.60 5.82

506.5 - 599.1

96.59

4.26x10-6

0.5 H2O Cl + HCL+C2H4OH +CH3 Partial decomp. of thiazole H2S + NH=CH C2H4 + 0.5 NH2 0.5 NH2 + Py(CH3)2 (Residue) 2H2O outer + H2O coord. 2.5H2O coord. 0.5 H2O + CH3 + C2H4OH H2 S C=N-C=C + CH3 + NH2 + Py-CH2 V2O3 (Residue) 0.5 outer H2O 0.5 outer H2O + 1.5 coord. H2O 0.5 coord. H2O + 2Cl C2H4OH +CH3 3Cl + partial decomp. of thiaz. (H2S) rest of L + Fe (Residue)

SC

RI PT

32.58 82.10

Removal species

5.10 (5.52)

1.5 outer H2O

5.30x10 2.63x10-4 9.47x10-8

13.99 (12.77) 22.33 (22.59) 3.55 (3.27)

5.06

24.59 (24.63)

0.5 outer H2O + one coord. H2O+Cl CH3 + C2H4OH +Cl + CH3 NH2 Cl + decomp.of thiaz. (H2S + C=N-C=C) Py-CH2 + Cu (Residue) H2O outer +H2O coord. Cl outer + 2CH3 + 2Cl coord.

-7

31.8-182.3 182.4-344.6

17.53 28.26

3.27x10 5.86x10-4

30.46 (31.39) 6.83 (7.62) 28.13 (28.8)

344.7-496.6

16.28

2.59x10-5

11.67 (10.59)

-5

53.3 (53.45)

NH2 + partial decomp. of thiaz. H2S Py-CH2 + C=N-C=C+ C2H4 + ZnO (Residue) 1.5 outer H2O 2Cl outer + Cl coord. 2 CH3 Rest of ligand +Co (Residue) H2O outer

46.6-167.1 167.1-329.4 329.4-496.9

34.16 33.00 15.71

4.34x10-3 2.08x10-3 2.99x10-5

38.3-171.1

11.74

4.70x10-6

6.19 (5.9) 23.98 (23.24) 6.61 (6.55) 63.22 (63.56) 2.50 (3.9)

171.1-320.2

56.50

2.04x10-6

36.63 (36.53)

Cl outer + CH3 + Cl inner + decop. of thiaz. H2S + C=N-C=C

320.2-461.3

57.10

0.056

32.58 (32.40) 28.30 (26.64)

C2H4 + CH3+NH2 + Py-CH2 PdO (Residue)

[Co(th)Cl]2Cl.1.5H2O

[Pd(th)Cl]Cl.H2O

23-163.6 163.7 - 268.7

Wt. loss % Found(Calc.%) 2.14(2.59) 37.13 (38.08)

AC C

[Zn(th)Cl2(H2O)]Cl.H2O

A (S-1)

M AN U

[(VO)2O(th)(H2O)4]2H2O

Ea (KJ/mol)

TE D

Thiamine Cl HCl

Temp. range (ºC )

EP

Compound

5 k/min

15

ACCEPTED MANUSCRIPT

9.89

3.10x10-6

8.75 (7.77)

196.7-350.5

37.59

5.65x10-3

45.13 (46.15)

350.5-494.8

53.12

0.056

35-175.2

11.80

1.27x10-5

33.92 (33.1) 12.18 (13.31) 11.23 (11.62)

175.2-351.1

24.85

3.93x10-4

44.13 (43.82)

351.1-499.1

47.13

0.023

32.52 (31.3) 12.17 (13.31)

[Pd(th)Cl]Cl.H2O

AC C

EP

TE D

M AN U

SC

25 k/min

H2O + 0.5 Cl outer 0.5 Cl outer + Cl coord.+2CH3 +C2H4 + NH2+ decomp. of thiaz. H2S + C=N-C=C Py-CH2 + 0.5 PdO 0.5 PdO (Residue) H2O + Cl outer 2CH3 + Cl + C2H4 + decomp. of thiaz.(H2S+C=N-C=C) + NH2 + 0.5 CH2 0.5 CH2 + Py +0.5 PdO 0.5 PdO (Residue)

RI PT

15 k/min

32.7-196.7

Figure (4): TGA/DTA curves of [(VO)2O(th)(H2O)4]2H2O complex. 16

ACCEPTED MANUSCRIPT

Table (6): DTA analysis of thiamine Cl HCl and its metal complexes.

n

αm

4 1.1 2.4 1.6 1.7 2.3 2.6 9.1 6.85 0.8 0.7 11.3 4.9 1 2.3 1.4 6.1 1.2 2.5 1.6 3.1

9 5.8 2 1.6 1.5 7 0.65 8.1 3.5 2.6 2.5 3.8 3.55 8.3 0.6 1.7 1.8 0.5 2.6 14.7 2.7

0.84 0.54 1.38 1.26 1.34 0.72 0.63 1.33 1.76 0.69 0.66 2.17 1.48 0.43 2.46 1.14

0.66 0.73 0.57 0.58 0.57 0.69 0.71 0.57 0.52 0.69 0.70 0.48 0.55 0.77 0.46 0.607

2.31 1.95 1.23 0.41 1.35

0.47 0.50 0.59 0.78 0.57

M AN U

TE D

17

E (KJ/mol) 37.32 73.13 134.52 Sharp peak 217.57 113.07 98.85 168.77 20.11 Sharp peak 26.23 91.53 134.52 Sharp peak 31.31 103.34 20.53 77.23 288.08

Z (S-1) 1.54 2.11 8.51 5.72 4.75 3.04 4.82 0.83 1.36 3.20 3.76 1.68 3.09

∆H# (kJ mol-1) -121.35 -173.54 -82.69 -189.58 -118.83 -161.81 -174.17 -122.22 -96.44 -142.46 -178.04 -92.60 -166.49

0.39 1.36 4.60

-135.91 -144.52 -161.09

∆S# kJ K-1 mol-1 -0.2455 -0.2459 -0.228 -0.238 -0.236 -0.242 -0.239 -0.25 -0.244 -0.240 -0.241 -0.2426 -0.2425 -0.25 -0.24 -0.23

33.92 227.30 170.35 11.51 200.11

1.85 11.88 7.56 1.043 14.61

-136.25 -142.38 -166.79 -138.71 -165.36

-0.24 -0.23 -0.23 -0.24 -0.22

RI PT

b

SC

a

EP

Tm (K) 494.3 705.9 359.1 638 794.1 502.9 667.7 728 487.9 730 394.2 591.3 737.5 853 381.7 686.7 528 583 677 556 618 705.8 558.4 718.8

AC C

Peak Type Endo Thiamine Cl HCl Endo Endo Exo [(VO)2O(th)(H2O)4]2H2O Exo Endo Endo [Fe(th)Cl3(H2O)2]2Cl.H2O Endo Endo [Zn(th)Cl2(H2O)]Cl.H2O Endo Endo Endo [Cu(th)Cl2(H2O)2]Cl.H2O Endo Exo Endo [Co(th)Cl]2Cl.1.5H2O Exo Endo 5 k/min Exo Exo Endo [Pd(th)Cl]Cl.H2O 15 k/min Exo Exo Endo 25 k/min Exo Compound

ACCEPTED MANUSCRIPT

Different heating rates for palladium complex: The calculation of activation energies can be obtained from a correlation between different heating rates (β) and peak temperatures Tp as follow (60):

RI PT

[d (ln β/Tp2)] = d(1/Tp)(-E/R) Where, E is the activation energy and R is the gas constant 8.314 J mol-1 K-1. A plot between (ln β/Tp2) against 1/Tp. E can be calculated from the slope of the plot according to the following equation: E= -[d(log β/Tp2)]/d(1/Tp)R x2.303.

KJ/mol

M AN U

SC

A relation between Ln(β/T²) and 1000/Tp, Figure (5) was plotted for [Pd(th)Cl]Cl.H2O complex at 5, 15 and 25 heating rates. Data are listed in Tables (7-8). The first peak has activation energy 106.83 KJ/mol, while the second peak has activation energy 144.82 KJ/mole. The activation energy for second one increased due to the high stability of the remaining part of the complex. From TGA thermograms, as the heating rate increased the activation energies are decreased as follows: Ea Pd (β =5) > Ea Pd (β =15) > Ea Pd (β =25)

TE D

Table (7): DTA data for Pd(II) complex at different heating rates. Peak (1)/(2) Heating rate (β) Tp(K) 1000/Tp Ln(β/T²) 528 / 677 2.893 / 1.47 -10.92 / -11.42 5 556 / 705.8 1.798 / 1.41 -9.93 / -10.41 15 558 / 718.3 1.792 / 1.39 -9.42 / -9.93 25

AC C

EP

Table (8): Activation energies of DTA curves for Pd(II) complex at different heating rates. Peak Slope Ea (KJ/mol) R2 -12.85 106.83 0.92 (1) -17.42 144.82 0.99 (2)

Figure (5): Correlation between different heating rates and peak temperatures for [Pd(th)Cl]Cl.H2O complex.

18

ACCEPTED MANUSCRIPT

c) Differential scanning calorimetry (DSC): The glass transition, crystallization and melting temperatures were determined from DSC graph for selected complexes, Table (9).

RI PT

Thiamine ligand has no glass transition temperature Tg as it has no thermal changes until 200 ᵌC, it is thermally stable and decomposes above this temperature which is compatible with the interpretation of TGA and DTA data. The glass transition temperature for all complexes can be determined from DSC graph since they show dehydration process due to lattice and coordinated water molecules followed by thermal agitation decomposition. This is compatible with the interpretation of TGA data for these complexes. The [Pd(th)Cl]Cl.H2O complex has no Tg even at different heating rates (5, 15 and 25 K/min).

M AN U

SC

The heat capacity can be determined by dividing the heat flow by the heating rate. The variation in specific heat (Cp) against temperature (T) is described by Debye model(61) and can be represented by using the following form(19): Cp = aT+ b, Where, a plot between Cp (the specific heat at constant pressure) as y-axis against T as x-axis and straight line is obtained with a and b parameters in which can be determined from the slope and intercept of the straight line, respectively. Further calculations based on Debye model from the following equations: Cp ≈ Cv = αT3 + γT

,

Cp T

= αT 2 + γ

TE D

By plotting Cp/T as y-axis against T2 as x- axis, a straight line is obtained with a slope α and intercept γ of the straight line. Where, α and γ are the coefficients of lattice and electronic capacities, respectively.

EP

By applying this model to the [(VO)2O(th)(H2O)4]2H2O complex as a demonstration, Figure (6), represents dependence of heat flow on temperature. From this curve, glass transition and crystallization temperatures could be determined. Figure (7) represents the dependence of specific heat on temperature and the variation of Cp/T with T2.

AC C

Table (9): Thermal transitions data for thiamine Cl HCl and its complexes. Compound Thiamine Cl HCl [(VO)2O(th)(H2O)4]2H2O

Tg 270

Tc 230 -

Tm 520 523.5

[Cu(th)Cl2(H2O)2]Cl.H2O [Fe(th)Cl3(H2O)2]2Cl.H2O [Zn(th)Cl2(H2O)]Cl.H2O

230 170 185

354.6 390 -

583.6 520 520

[Co(th)Cl]2Cl.1.5H2O

190

-

520

-

255 285 290

404 434 445

[Pd(th)Cl]Cl.H2O

(5 k/min) (15 k/min) (25 k/min)

19

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

Figure (6): DSC curve for [(VO)2O(th)(H2O)4]2H2O.

Figure (7): The variation of Cp versus T and Cp/T versus T2 for [(VO)2O(th)(H2O)4]2H2O.

20

ACCEPTED MANUSCRIPT

Molecular modeling:

RI PT

Figure (8) is given for illustration. Thiamine Cl HCl has different coordination sites N(2), N(6), S(11) of thiazole, N(15) of amino group and O(18) of hydroxyl group carrying charges -0.396, -0.428, 0.632, 0.03 and -0.39, respectively, are proposed as potential sites for coordination with different metal ion centers.

SC

All C-H are in the range 1.11±0.01Å. The bond lengths of N(15)-H(29) and N(15)-H(30) are 1.05 Å, while for O(18)-H(35) is 0.96 Å. All C-C bond lengths lie in the range 1.37-1.53 Å, when the carbon atom is replaced by oxygen or nitrogen it leads to a shorten bond length, due to their electronegativity character. The bond lengths of C(7)-S(11) and C(10)-S(11) have highest values 1.68 Å and 1.73 Å, respectively. The values of bond lengths for all C-N are nearly the same within the range 1.34-1.42 Å, except for N(9)-C(12) is 1.53 Å. The C(17)-O(18) bond length is 1.41 Å. The bond length for Cl(37)H(38) is 1.34 Å.

M AN U

Most of the bond angles between atoms in thiamine Cl HCl lie around 109.5ᵒ and 120ᵒ due to the sp2 and sp3 hybridization of atoms. The deviations from these angles are due to distorted electronic effects and steric hindrance resulting from the two rings pyrimidine (six membered) and thiazole (five membered) for N(6)-C(1)-N(2), C(16)-C(7)-C(8), C(13)-C(8)-C(7), and C(12)-N(9)-C(8). The deviation in the bond angle 89.26ᵒ is due to distorted electronic effects for C(10)-S(11)-C(7).

TE D

However, the most dihedral angles in thiamine lie in ranges around ±0ᵒ and ±180ᵒ. The dihedral angles of zero range lie around -25.22ᵒ -29.97ᵒ in case of, C(10)-N(9)-C(8)-C(7), C(4)-C(12)-N(9)-C(8), N(6)C(5)-N(15)-H(29), C(4)-C(5)-N(15)-H(30), C(4)-C(5)-N(6)-C(1), N(2)-C(1)-N(6)-C(5), C(3)-N(2)-C(1)N(6), C(12)-C(4)-C(3)-H(19), C(5)-C(4)-C(3)-N(2), N(15)-C(5)-C(4)-C(12), N(6)-C(5)-C(4)-C(3), C(12)-N(9)-C(10)-H(20), C(8)-N(9)-C(10)-S(11), C(7)-C(8)-C(13)-H(23),C(7)-S(11)-C(10)-N(9), N(6)C(1)-C(14)-H(27), C(8)-C(7)-S(11)-C(10), C(3)-C(4)-C(12)-H(22), C(13)-C(8)-C(7)-C(16), N(9)-C(8)C(7)-S(11), C(12)-N(9)-C(8)-C(13), S(11)-C(7)-C(16)-H(31), N(9)-C(8)-C(13)-H(25) and C(4)-C(3)N(2)-C(1).

AC C

EP

The dihedral angles around ±180ᵒ lie in antiperiplanar position in the range -150.4ᵒ to -179.9ᵒ and 167.8ᵒ to 179.35ᵒ exist in N(15)-C(5)-N(6)-C(1), C(14)-C(1)-N(6)-C(5), C(3)-N(2)-C(1)-C(14), H(19)-C(3)N(2)-C(1), C(12)-C(4)-C(3)-N(2), C(5)-C(4)-C(3)-H(19), N(15)-C(5)-C(4)-C(3), N(6)-C(5)-C(4)-C(12), C(16)-C(17)-O(18)-H(35), (N(9)-C(8)-C(7)-C(16), C(7)-S(11)-C(10)-H(20), C(8)-N(9)-C(10)-H(20), C(13)-C(8)-C(7)-S(11), C(10)-N(9)-C(8)-C(13), C(12)-N(9)-C(8)-C(7), C(12)-N(9)-C(10)-S(11), H(32)C(16)-C(17)-H(34), H(31)-C(16)-C(17)-H(33), C(4)-C(5)-N(15)-H(29), N(6)-C(5)-N(15)-H(30), C(16)C(7)-S(11)-C(10), C(5)-C(4)-C(12)-H(22), C(4)-C(12)-N(9)-C(10), C(8)-C(7)-C(16)-H(31), C(7)-C(16)C(17)-O(18) and N(2)-C(1)-C(14)-H(27). Some deviations refer to the distortion of sp3 hybridization linearity. The values (±0ᵒ - ±180ᵒ) proved the near planarity of thiamine molecule, and also different values referred to the different arrangements of atoms, where the dihedral angle of 0ᵒ is referred to synperiplanar position, while, the 180ᵒ one is referred to antiperiplanar position. However, the dihedral angles around 59.43 to 88.32 and -33.8406 to -60.59 refer to a large deviation from the perpendicular position which ascribed to distortion effects. These dihedral angles have a synclinal arrangements.

21

RI PT

ACCEPTED MANUSCRIPT

SC

Figure (8): Perspective view and labeling scheme of thiamine Cl HCl model.

M AN U

Application of Hyper chemistry program:

TE D

Quantum chemical parameters such as the highest occupied molecular orbital energy (EHOMO), the lowest unoccupied molecular orbital energy (ELUMO), energy gap (∆E) and those parameters that give valuable information about the reactive behavior such as electronegativity (χ), chemical potential (Pi), global hardness (η) and softness (σ), were calculated, Table (10). These calculations are based on neglecting the possibility of hydrogen bonding. These parameters are in a close relation to each other where, (EHOMO) and (ELUMO) are directly related to the ionization potential (I) and the electron affinity (A), respectively as follows (24): Ι = − Ε HOMO Α = − Ε LUMO The chemical potential (Pi) is given from these relations:

Pi = − χ

EP

Pi =

− (Ι + Α ) Ε HOMO + Ε LUMO = 2 2

AC C

The hardness term has been described on the basis of the energy gap (∆E). It is related to the polarizability, as the decrease in the energy gap (∆E) give easier polarization of the molecule(62).

η =

Ι − Α (Ε LUMO − Ε HOMO = 2 2

)

The inverse value of hardness is nominated as softness, (σ) and is calculated from the following relation: 1 σ =

η

The electrophilicity index (ω), is a measure of energy lowering due to the maximum flow of electron between donor and acceptor. It is related to chemical potential (Pi) and hardness (η ) as follows: Pi 2 ω = 2η

22

ACCEPTED MANUSCRIPT

In this study, the methylene bridge helps to keep the two aromatic rings separate, therefore, keeps the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are located on separate rings, Figure (9). This allows thiamine to react on different rings towards electrophiles and nucleophiles.

RI PT

The energy gap for all complexes is in the range 3.58-6.54 ev compared to ligand (7.09 ev). However, hardness of ligand is 3.54 ev, where, all complexes are in the range 1.79-3.27 ev, while, softness of all complexes is in the range 0.30-0.55 ev compared to thiamine Cl HCl (0.28 ev). So, all complexes acted as a soft molecules indicating more reactivity for all complexes.

TE D

M AN U

SC

The electrophilicity index (ω) of free ligand and its complexes ranged between 2.33-12.74 ev and the chemical potential (Pi) between -2.89 to -8.19 ev. The electronegativity (χ) ranged between 2.89-8.19 ev. The ionization potential (I) ranged between 4.68-10.75 ev, while the electron affinity (A) ranged between 1.10-5.75 ev.

Figure (9): HOMO and LUMO of thiamine Cl HCl.

EP

Table (10): Quantum chemical parameters for thiamine and its complexes by (PM3) method. EH -8.42 -7.43 -7.40 -8.80 -5.48 -4.68 -8.25 -7.99 10.75 -6.50 10.64 -8.29

AC C

Compound Thiamine Cl HCl [(VO)2O(th)(H2O)4]2H2O [Mn(th)Cl(H2O)3]3Cl.H2O [Fe(th)Cl3(H2O)2]2Cl.H2O [Co(th)Cl]2Cl.1.5H2O [Ni(th)Cl2]2Cl.3H2O [Cu(th)Cl2(H2O)2]Cl.H2O [Zn(th)Cl2(H2O)]Cl.H2O Se2(th)2(H2O)2 [Pd(th)Cl]Cl.H2O [(WO2)(th)Cl(H2O)]Cl [Hg(th)Cl2(H2O)]Cl

EL -1.33 -2.04 -1.72 -3.95 -1.66 -1.10 -1.79 -2.71 -5.44 -1.29 -5.75 -1.75

∆E 7.09 5.39 5.68 4.85 3.82 3.58 6.46 5.28 5.34 5.21 4.89 6.54

χ 4.87 4.74 4.56 6.37 3.57 2.89 5.02 5.35 8.09 3.89 8.19 5.02

23

Pi -4.87 -4.74 -4.56 -6.37 -3.57 -2.89 -5.02 -5.35 -8.09 -3.89 -8.19 -5.02

η 3.54 2.69 2.84 2.42 1.91 1.79 3.23 2.64 2.65 2.60 2.44 3.27

Σ 0.28 0.37 0.35 0.41 0.52 0.55 0.31 0.38 0.37 0.38 0.40 0.30

ω 3.35 4.17 3.66 8.38 3.33 2.33 3.90 5.42 12.34 2.90 13.74 3.85

I 8.42 7.43 7.40 8.80 5.48 4.68 8.25 7.99 10.75 6.50 10.64 8.29

A 1.33 2.04 1.72 3.95 1.66 1.10 1.79 2.71 5.44 1.29 5.75 1.75

ACCEPTED MANUSCRIPT

Structural interpretation:

M AN U

SC

RI PT

The structures of the complexes of thiamine Cl HCl, with VO2+, Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Se(IV), Pd(II), WO2- and Hg(II) ions were confirmed by elemental analyses, IR, UV-Vis, NMR, molar conductance, magnetic properties, EDX, and thermal analysis data. Therefore, from IR results, it was concluded that thiamine Cl HCl ligand acts as a bidentate ligand for VO2+, Mn(II), Ni(II), Cu(II), Se(IV), and (WO2) complexes through the sulphur atom of thiazole ring and (N1) in pyrimidine ring. In the latter complexes, thiamine Cl HCl acts as a tridentate ligand coordinating through OH group, N1 and S donor atoms in case of Co(II), Pd(II), Zn(II) complexes, while for Hg(II) complex it coordinates through OH group, sulphur atom and NH2 group. It seems that thiamine acts as a monodentate ligand in case of Fe(III) complex through the sulpur atom. From the molar conductance data, it was found that the Cu(II), Zn(II), Pd(II), WO2- and Hg(II) complexes are considered as 1:1 electrolytes, while Fe(III), Co(II) and Ni(II) complexes are considered as 1:2 electrolytes and Mn(II) complex is 1:3 electrolyte. On the other hand, (VO)2 and Se (IV) complexes are non-electrolytes. Octahedral geometry is suggested for Mn(II), Fe(III), Cu(II), Zn(II), WO2- and Hg(II) complexes, square planar for Se(IV) and Pd(II) complexes, square pyramidal for VO2+ complex and tetrahedral geometry is suggested for Co(II) and Ni(II) complexes. Correlation analysis:

ELUMO and EHOMO of ligand and its complexes with the IR data, Figure (10), Table (11), gave a negative slope (-0.06) of the linear relationship between ∆E and stretching frequencies ν (M-S) of complexes assigned to an inverse relationship. This leads to decrease in ∆E associated with shift in stretching frequencies of ν(M-S) with a correlation coefficient 0.85 indicating a strong association.

TE D

The M-S bond lengths of metal complexes and IR data ν(M-S), Figure (11), Table (11), gave negative slope (-0.004) of the linear relationship of inverse relationship. This gives decrease in bond lengths (Å) associated with shift in stretching frequencies of ν(M-S) by a strong association represented by a correlation coefficient 0.94.

EP

The λmax of metal complexes and their magnetic properties, Figure (12), Table (11) gave a negative slope (-5.79) of the linear relationship between both variables of complexes. This inverse relationship showing the decrease in wavelength associated with increase in magnetic moments by an association represented by a correlation coefficient 0.93.

AC C

The correlation between the molecular weight of thiamine and its metal complexes and their melting temperatures, Figure (13), Table (11), gave positive slope (2.95) of the linear relationship between the both variables of compounds indicated positive relationship showing the increase in melting temperature associated with increase in their molecular weights by a moderate association represented by a correlation coefficient 0.69.

24

SC

RI PT

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

Figure (10): Correlation of ∆E (ev) versus the Figure (11): Correlation of Bond lengths (Å) versus stretching frequency ν(M-S) cm-1. stretching frequencies ν(M-S) cm-1.

AC C

Figure (12): Correlation of λmax (nm) versus the magnetic susceptibility of complexes.

Figure (13): Correlation of M.wt versus the melting temperature of compounds.

Table (11): Correlation coefficients and slopes of relationships. Figure 12 13 14 15

Slope -0.06 -.004 -5.79 2.95

25

Correlation coefficient 0.85 0.94 0.93 0.69

ACCEPTED MANUSCRIPT

References

AC C

EP

TE D

M AN U

SC

RI PT

1- G. F. Combs, “The vitamins: Fundamental Aspects in Nutrition and Health”, 3rd Edn. (2008). 2- D. A. Bender, “Nutritional Biochemistry of the vitamins”, 2nd Edn. (2003). 3- E. J. Vandamme,” Biotechnology of Vitamins, Pigments and Growth Factors. ©1989 Elsevier Science Publishers, Ltd. 4- J. Zempleni, R. B. Rucker, D. B. McCormick, J. W. Suttie and Ch. J. Bates, “Hand book of vitamins”, 4th Edn.(2007). 5- M. B. Hursthouse, K. M. Abdul Malik, P. K. Bakshi, A. A. Bhuiyan, M. Q. Ehsan, and S. Z. Haider, J. Chem. Cryst., 26 (11): 739-745 (1996). 6- M. Louloudi and N. Hadjiliadis, Coord. Chem. Rev., 135-136: 429-468 (1994). 7- A. C. Tella and J. A. Obaleye, Orbital: Electron. J. Chem., 2(1): 11-26 (2010) . 8- M. S. Masoud, A. El-Merghany and M. Y. Abd El-Kaway, Synth. React. Inorg. Met.-Org. Nano-Met. Chem., 39, 537–553(2009). 9- M. S. Masoud, A. M. Ramadan and G. M. El-Ashry, Thermochim Acta., 551, 164-174 (2013). 10- M. S. Masoud, A. A. Soayed and A. F. El-Husseiny, , Spectrochim Acta A., 99, 365-372 (2012). 11- M. S. Masoud, A. El-Marghany, A. Orabi, A. E. Ali and R. Sayed, Spectrochim Acta A., 107, 179187 (2013). 12- M. S. Masoud, A. E. Ali, M. A. Shaker and G. S. Elasala, Spectrochim. Acta A., 90, 93-108 (2012). 13- M. S. Masoud, S. S. Hagagg, A. E.Ali and N. M. Nasr, J. Mol. Stru., 1014, 17-25 (2012). 14- M. S. Masoud, A. E. Ali and M. Y. Abd El-Kaway, J. Therm. Anal. Cal.,116, 183-194 (2014). 15- M. S. Masoud, A. E. Ali, M. A. Shaker and G. S. Elasala, Spectrochim. Acta A., 90 (1): 93-108 (2012). 16- M. S. Masoud, R. H. A. Mohamed, A. E. Ali and N. O. M. EL-Ziani, J. Chem. Pharm. Res., 8(1):639662 (2016). 17- M. S. Masoud, A. E. Ali, D. A. Ghareeb, N. M. Nasr, J. Mol. Struc., 1107: 189-201 (2016). 18- M. S. Masoud, A. E. Ali, D. A. Ghareeb and N. M. Nasr, J. Mol. Struc., 1099: 359-372 (2015). 19- M. S. Masoud, A. E. Ali, and G. S. Elasala, J. Mol. Struc., 1084: 259-273 (2015). 20- G. Schwarzenbach, "Complexometric Titration", Translated by H. Irving, Methuen Co., London, (1957). 21- A. I. Vogel, "A Text Book of Quantitative Inorganic Analysis", Longmans, London (1989). 22- D. Reinen and C. Friebel, Inorg. Chem., 23, 791 (1984). 23- B. N. Figgis and J. Lewis, "Modern Coordination Chemistry", Interscience, New York, :403(1967). 24- M. S. Masoud, M. K. Awad, M. A. Shaker and M. M. T. El-Tahawy, Corr. Sci., 52 (7): 2387-2396 (2010). 25- A. A. Shaik, S. Akter, M. S. Rahman and P. K. Bakshi, J. Bangladesh Acad. Sci., 35 (1): 51-59 (2011). 26- N. Hadjiliadis, A. Yannopoulos and R. Bau, Inorg. Chim. Acta, 69: 109-115(1983). 27- N. Hadjiliadis, J. Markopoulos, G. Pneumatikakis and D. K. T. Theophanides, Inorg. Chim. Acta, 25: 21-31(1977). 28- M. Louloudi, N. Hadjiliadis, Jin-An F., S. Sukumar and R. Bad, J. Am. Chem. SOC., 112: 7233-7238 (1990). 29- A. O. Adeyemo, G. A. Kolawole and E. Archibong, Inorg. Chim. Acta, 165: 255 -258 (1989). 30- J. Gary and A. Adeyemo, Inorg. Chim. Acta., 55: 93-98 (1981). 31- S. A. El-Shazly, M. M. Ahmed , Z. Sh. Ibrahim and M. S. Refat, Int. J. Immunopathol. Pharmacol., 1–13(2015). 26

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

32- M. N. Vinayak, G. T. Kuchinad, S. K. Patil and N. B.Mallur, Der Pharma. Chemica. 5(4):4350(2013). 33- A. C. González-Baró and E. J.Baran, J. Braz. Chem. Soc., 12 (2): 208-214 (2001). 34- A. S. Thakar, K. S. Pandya, K. T. Joshi and A. M. Pancholi, E-J. Chem. 8 (4): 1556-1565 (2011). 35- M. S. Masoud, O. H. Abd El- Hamid and Z. M. Zaki, Trans. Met. Chem, 19: 21-24 (1994). 36- C. Anitha, C. D. Sheela, P. Tharmaraj and R. Shanmugakala, Int. J. Inorg. Chem. 2013: 1-10 (2013). 37- A. A. A. Abou-Hussein and W. Linert, Spectrochim. Acta A: Mol. & Biomol. Spectrosc. 95:596609(2012). 38- F. A. O. Adekunle, International Journal of Basic & Applied Sciences. 13 (3): 6-10 (2013). 39- N. L. Allinger, J. C. Tai and M. A. Miller, J. Am. Chem. Soc, 88 (19): 4495-4499 (1966). 40- H. A. Bayoumi, A. M. A. Alaghaz and M. Sh. Aljahdali, Int. J. Electrochem. Sci., 8: 9399-9413 (2013). 41- M. Louloudi, D. Kovala-Demertzi and N. Hadjiliadis, Bull. Soc. Chim. Belg. 97 (2): 91-97(1988). 42- S. E. Livingstone, Quart. Rev. Chem. Soc. 19: 386 (1965), , L. F. Finday, Coord. Chem. Rev., 4: 41(1969). 43- A. H. Atta, A. I. El-Shenawy, F. A. Koura and M. Refat, World J. Nano Sci. Eng. 4: 58-69 (2014). 44- S. Tettech, D. K. Dodoo, R. Appiah-Opong, and I. Tuffour, J. Inorg. Chem., 2014: 1-7 (2014). 45- M. S. Masoud, S. S. Haggag and E. A. Khalil, Nucleot. Nucl., 25:73-87(2006). 46- N. Nikolis, C. Methenitis, G. Pneumatikakis and M. M. L. Fiallo, J. Inorg. Biochem. 89: 131141(2002). 47- M. S. Masoud and M. M. El-Essawi, J. Chem. Eng. Data., 29(3): 363-367(1984). 48- M. S. Masoud, S. A. Abou El-Enein, M. E. Ayad and A. S. Goher, Spectro Chim. Acta, A 60: 70 (2004). 49- H. A. El-Boraey, S. M. Eman, D. A. Talon and A. M. El-Nahas, Spectrochim. Acta A 78: 360 (2011). 50- M. S. Masoud, E. A. Khalil, A. M. Hafez and A. F. El-Husseiny, Spectrochim. Acta, A 61: 989-993 (2005). 51- M. S. Masoud, A. A. Soayed, A. E. Ali and O. K. Sharsherh, J. Coord. Chem., 56 (8), 725-742 (2003). 52- M. S. Masoud and M. Y. Abd El-Kaway, Spectrochim. Acta Part A: Mol. & Biomol. Spectrosc. 102: 175-185 (2013). 53- A. Fuliaş, G. Valse, T. Valse, D. Oneţie, N. Doca and I. Ledeţi, J. Therm. Anal. Calorim., 118:10331038 (2014). 54- B. K. Dwivedi and R. G. Arnold. J. Agric. Food Chem. 21(1): 54 (1973). 55- A. W. Coats and J. P. Redfern, Kinetic parameters from Thermogravimetric Data, Nature publishing group. 201 (4914): 68-69 (1964). 56- R. H. Abu-Eittah, M. K. Khedr, Spectrochem. Acta. 71A:1688-1689 (2009). 57- H. E. Kissinger, Reaction kinetics in differential thermal analysis, Anal. Chem, 29 (11), 1702-1706 (1957). 58- H. Horowitz and G. Metzger, Anal. Chem, 35 (10): 1464-1468 (1963). 59- G. O. Piloyan, I. D. Ryabchicov and O. S. Novikova, Nature. 5067: 1229(1966). 60- T. Hatakeyama and Zhenhalliu "Willey-Hand book of Thermal analysis" 72 (1999). 61- C. Degueldre, P. Tissot, H. Lartigue and M. Pouchon, Thermochim. Acta., 403 (2):267-273 (2003). 62- R.G. Parr, R.G. Pearson, J. Am. Chem. Soc., 105: 7512(1983).

27

ACCEPTED MANUSCRIPT

Synthesis, characterization, spectral, thermal analysis and computational studies of thiamine complexes

RI PT

Highlights

AC C

EP

TE D

M AN U

SC

1- Structures of complexes were confirmed by elemental analysis, IR, UV-Vis, NMR, molar conductance, magnetic properties, EDX and thermal analysis. 2- Octahedral geometry suggested for Mn(II), Fe(III), Cu(II), Zn(II), WO2- and Hg(II) complexes, square planar for Se(IV) and Pd(II) complexes, square pyramidal for VO2+ complex and tetrahedral for Co(II) and Ni(II) complexes. 3- The thermodynamic parameters were estimated from the TGA and DTA curves. 4- Correlation analysis was done to explore the relationships between some different parameters of the studied complexes.