Journal of Molecular Structure-theochem, Mar 1, 2006
The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity o... more The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity of this drug, was investigated by DFT calculations at the B3LYP/6-311G (d) level of theory. The repulsion forces, existing within the molecule because of the simultaneous presence of the acetate moiety as well as the two Cl atoms, created a twisted (748) diphenylamine structure to yield a preferred orientation. B3LYP/ 6-311G (d) calculations of diclofenac and its complexes, ML 2 (LZCa, Mg, Zn), showed that distortions of the geometric parameters were due to the differing hybridizations depending on the cation type in question. The energy gap values, DE, increased in the order MgOZnOCa, pointing out that the energy associated with electron pairing is greatest in the Mg 2C complex, due to the [Ne]3s 2 configuration and large charge to radius ratio (3.3) of the metal. The charge density contour plots of the complexes showed the negative charge as condensed around the N atom, indicating a very highly polarized M-N coordinate bond. Both the acid form and sodium salt displayed the typical weak N-H/O hydrogen bond association which is absent in the Mg, Ca and Zn complexes. The distance between H and O in all three (3.837 Mg, 3.307 Ca and 4.277 Zn Å) exceeded the possible limit of 3.0 Å .
European Journal of Pharmaceutical Sciences, Nov 1, 2005
IR, 1 H NMR and mass spectrometric studies showed that cetirizine dihydrochloride interacted stro... more IR, 1 H NMR and mass spectrometric studies showed that cetirizine dihydrochloride interacted strongly with diclofenac sodium, even when the latter was metal bound, forming high molecular weight stable adducts. These new formations were unaffected by the possible steric constraints that may exist because of coordination yet did not have the power to break the formed coordinate bonds. The formed ionic bond took place between the carbonyl ion of diclofenac and the positively charged piperazine ring of cetirizine, forming a ternary compound in the case of the divalent metal clusters (Ca{(dic) 2 •2H 2 O}, Mg{(dic) 2 •2H 2 O}, Zn{(dic) 2 •2H 2 O}) and a quaternary one with the trivalent iron cluster (Fe{dic} 3 •3H 2 O). IR bands assigned to νNH, δNH and νC N were shifted to lower frequency values in the spectra of the complexes; thus showing that coordination took place at the NH of the diphenylamine. TG and elemental analysis confirmed these results.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Sep 1, 2011
3-Amino-1,2,4-triazole Schiff bases were reported to contain intramolecular charge-transfer. The ... more 3-Amino-1,2,4-triazole Schiff bases were reported to contain intramolecular charge-transfer. The enhancing and depressing effects were remarkable as the substituent was changed from electron-donating to electron-withdrawing groups. The path of the resonating delocalization was reversed in the case of the p-NO 2 group. To validate these results we effectively used Weinhold et al's natural bond orbital analysis to assess the UV and FT-IR spectrophotometric monitoring of the change reflected in this phenomenon when the substituent in the benzene ring is altered. The NBO analysis was simulated by ab inito computations at the HF/6-31G(d) level of theory, in order to properly detect any possible presence of a hydrogen bond association. The changes occurring in electron occupancies of double-centered bonds, antibonding orbitals and in lone-pair orbitals appraised the results, as did the s and p character listings of the twocentered bonds and the simultaneous changes occurring in the geometric parameters of the molecules in question. Contrary to its normal preference, in these molecules the nitrogen used sp 2 hybrid orbitals for its interaction, housing its electron lone-pair in the third p hybrid orbital. Furthermore, NBO analysis reflected the presence of a very soft intramolecular hydrogen association (C-H• • •), labelled by UV and FT-IR assignments, between the benzene and triazole rings in all Schiff bases but p-N(Me) 2. The n-* stabilization energy decreased in the order: p-OH > p-OCH 3 > p-Cl > p-CH 3 > H > p-NO 2 > o-OH. The relation between the band position and Hammett substitution constant is interpreted in relation to the molecular structure.
Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decre... more Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decreasing trend of the onset decomposition temperatures at which these compounds dissociated. The drop in the temperature was metal ion dependent; the sodium salt showed thermal stability up to 245 8C, whereas the complexes started their degradation processes at temperatures starting from 90 8C. While G* for the cleavage of the acetate moiety in the sodium salt was 63.76 kJmol K1 , it was 82.06 and 140.57 kJmol K1 in the cases of Ca 2C and Fe 3C , respectively. However, their complete fusion took place at 187.65, 150.34 and 98.77 8C, respectively, displaying a reversed trend which is probably indicative of some catalytic part on the binding metals. Using the Gaussian 98 W package of programs, ab initio molecular orbital treatments were applied to diclofenac and its Ca 2C and Fe 3C metal complexes to study their electronic structure at the atomic level. The thermochemistry of diclofenac sodium was followed through the TG fragmentation peak temperatures using the density functional theory calculations at the 6-31G(d) basis set level. The FT-IR data were in good agreement with the theoretically calculated values. Single point calculations at the B3LYP/ 6-311G(d) level of theory, were used to compare the geometric features, energies and dipole moments of these compounds to detect the effect of the binding metal ions on the thermal dissociation of their diclofenac complexes.
This work deals with a concise survey of some techniques that were used by different authors to d... more This work deals with a concise survey of some techniques that were used by different authors to determine experimentally the static dipole polarizability ranging from index of refraction measurements to optical, electrical or spectroscopic studies. A short discussion of the consequent ...
Journal of Pharmaceutical and Biomedical Analysis, Apr 1, 2005
The interactions between diclofenac (1), cetirizine (2) and ranitidine (3) were investigated by t... more The interactions between diclofenac (1), cetirizine (2) and ranitidine (3) were investigated by thermal analyses and UV, IR and (1)H NMR spectroscopic studies. In aqueous solution interaction occurred only between 1 and 2, yielding a high molecular weight (1:1), water insoluble ionic salt. Weak charge transfer (CT) interaction exists between the doubly charged piperazine moiety in 2, acting as an electron acceptor and (1). This CT interaction originates from the aromatic groups in 1. The CT band observed at approximately 315 nm exhibits very low absorbance as a result of the partial neutralization of the two positive charges present in the ionic salt. The IR bands of the mixture have wave numbers at nu 3323.1, 1695.3, and delta 1321.1-1210 cm(-1) indicating the presence of the NH group and the neutralized carbonyl group of 1, as well as the carboxylic group of 2. The 1,2,3-substitutions in the benzene ring of 1 in the mixture appear at 1161.1 cm(-1). The (1)H NMR of the mixed drugs shows singlet, triplet and multiplet proton signals due to the same effect.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Nov 1, 2006
Ab initio calculations, FT-IR and X-ray crystal analysis, indicated that the most stable configur... more Ab initio calculations, FT-IR and X-ray crystal analysis, indicated that the most stable configuration of 3-oxo-2-(phenylhydrazono)-3-(thien-2-yl)-propionitrile is the anti phenylhydrazone structure 1. Stability of such a conformation, over the possible E-form, 2, that would be stabilized by intramolecular hydrogen bonding, is due to interaction between electron-pair domains of the N, S and O atoms. However, the simulated and experimental IR frequency data indicated intermolecular hydrogen bonding between NH and CN, the latter being lowered to 2214 cm(-1). Studies on 3-oxo-3-phenyl-2-(phenylhydrazono)-propionitrile showed the same result, as well as, another intramolecular hydrogen association of the type N-H...O. This was clearly indicated by the absorbance of the carbonyl stretch at 1605 cm(-1). These data indicated the existence of a bifurcated hydrogen bond in 1a and a single intermolecular association in 1b.
To avoid the problem of basis set completeness and superposition error effects, various basis set... more To avoid the problem of basis set completeness and superposition error effects, various basis sets (including polarized and diffuse functions) have been implemented, at the Hartree-Fock and density functional levels of theory, to calculate the molecular static dipole polarizability and first dipole hyperpolarizability for the ground state of diclofenac sodium. Sophisticated ab initio methods did not favour the results. Comparison with the experimentally obtained value of the total molecular polarizability of diclofenac sodium indicated that the Hartree-Fock level of theory using the medium basis set 6-31G(d) extended with a p and d polarized functions was best suited for the description of such an electrical property. The total molecular static dipole polarizability was 429 m 3 as compared to the experimental value of 419 m 3 . The corresponding mean and anisotropy of the molecular dipole polarizability converged at 176.76 and 76.19 au, respectively. The intrinsic dipole moment was found to be 6.5571 D. The hyperpolarizability was studied theoretically applying the same selected basis sets and levels of theory as those chosen to calculate the polarizability. The mean hyperpolarizability, b, was found to be of almost the same value when using the medium basis set 6-31G(d) and the corresponding mildly extended basis set 6-31G(p,2d) at the HF level of theory. The incorporation of electron correlation effects, as in the DFT methods yielded exceedingly larger b values, increasing up to 1153 au. These high values are, probably, attributed to the charge-transfer existing between the phenyl rings within the molecular skeleton. The electronic charge distribution of the dic molecule is displayed by the NBO analysis of atomic charges calculated at the B3LYP/6-31G(d) level of theory.
This work deals with a concise survey of some techniques that were used by different authors to d... more This work deals with a concise survey of some techniques that were used by different authors to determine experimentally the static dipole polarizability ranging from index of refraction measurements to optical, electrical or spectroscopic studies. A short discussion of the consequent ...
The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity o... more The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity of this drug, was investigated by DFT calculations at the B3LYP/6-311G (d) level of theory. The repulsion forces, existing within the molecule because of the simultaneous presence of the acetate moiety as well as the two Cl atoms, created a twisted (748) diphenylamine structure to yield a preferred orientation. B3LYP/ 6-311G (d) calculations of diclofenac and its complexes, ML 2 (LZCa, Mg, Zn), showed that distortions of the geometric parameters were due to the differing hybridizations depending on the cation type in question. The energy gap values, DE, increased in the order MgOZnOCa, pointing out that the energy associated with electron pairing is greatest in the Mg 2C complex, due to the [Ne]3s 2 configuration and large charge to radius ratio (3.3) of the metal. The charge density contour plots of the complexes showed the negative charge as condensed around the N atom, indicating a very highly polarized M-N coordinate bond. Both the acid form and sodium salt displayed the typical weak N-H/O hydrogen bond association which is absent in the Mg, Ca and Zn complexes. The distance between H and O in all three (3.837 Mg, 3.307 Ca and 4.277 Zn Å) exceeded the possible limit of 3.0 Å .
Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decre... more Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decreasing trend of the onset decomposition temperatures at which these compounds dissociated. The drop in the temperature was metal ion dependent; the sodium salt showed thermal stability up to 245 8C, whereas the complexes started their degradation processes at temperatures starting from 90 8C. While G* for the cleavage of the acetate moiety in the sodium salt was 63.76 kJmol K1 , it was 82.06 and 140.57 kJmol K1 in the cases of Ca 2C and Fe 3C , respectively. However, their complete fusion took place at 187.65, 150.34 and 98.77 8C, respectively, displaying a reversed trend which is probably indicative of some catalytic part on the binding metals. Using the Gaussian 98 W package of programs, ab initio molecular orbital treatments were applied to diclofenac and its Ca 2C and Fe 3C metal complexes to study their electronic structure at the atomic level. The thermochemistry of diclofenac sodium was followed through the TG fragmentation peak temperatures using the density functional theory calculations at the 6-31G(d) basis set level. The FT-IR data were in good agreement with the theoretically calculated values. Single point calculations at the B3LYP/ 6-311G(d) level of theory, were used to compare the geometric features, energies and dipole moments of these compounds to detect the effect of the binding metal ions on the thermal dissociation of their diclofenac complexes.
Journal of Molecular Structure-theochem, Mar 1, 2006
The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity o... more The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity of this drug, was investigated by DFT calculations at the B3LYP/6-311G (d) level of theory. The repulsion forces, existing within the molecule because of the simultaneous presence of the acetate moiety as well as the two Cl atoms, created a twisted (748) diphenylamine structure to yield a preferred orientation. B3LYP/ 6-311G (d) calculations of diclofenac and its complexes, ML 2 (LZCa, Mg, Zn), showed that distortions of the geometric parameters were due to the differing hybridizations depending on the cation type in question. The energy gap values, DE, increased in the order MgOZnOCa, pointing out that the energy associated with electron pairing is greatest in the Mg 2C complex, due to the [Ne]3s 2 configuration and large charge to radius ratio (3.3) of the metal. The charge density contour plots of the complexes showed the negative charge as condensed around the N atom, indicating a very highly polarized M-N coordinate bond. Both the acid form and sodium salt displayed the typical weak N-H/O hydrogen bond association which is absent in the Mg, Ca and Zn complexes. The distance between H and O in all three (3.837 Mg, 3.307 Ca and 4.277 Zn Å) exceeded the possible limit of 3.0 Å .
European Journal of Pharmaceutical Sciences, Nov 1, 2005
IR, 1 H NMR and mass spectrometric studies showed that cetirizine dihydrochloride interacted stro... more IR, 1 H NMR and mass spectrometric studies showed that cetirizine dihydrochloride interacted strongly with diclofenac sodium, even when the latter was metal bound, forming high molecular weight stable adducts. These new formations were unaffected by the possible steric constraints that may exist because of coordination yet did not have the power to break the formed coordinate bonds. The formed ionic bond took place between the carbonyl ion of diclofenac and the positively charged piperazine ring of cetirizine, forming a ternary compound in the case of the divalent metal clusters (Ca{(dic) 2 •2H 2 O}, Mg{(dic) 2 •2H 2 O}, Zn{(dic) 2 •2H 2 O}) and a quaternary one with the trivalent iron cluster (Fe{dic} 3 •3H 2 O). IR bands assigned to νNH, δNH and νC N were shifted to lower frequency values in the spectra of the complexes; thus showing that coordination took place at the NH of the diphenylamine. TG and elemental analysis confirmed these results.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Sep 1, 2011
3-Amino-1,2,4-triazole Schiff bases were reported to contain intramolecular charge-transfer. The ... more 3-Amino-1,2,4-triazole Schiff bases were reported to contain intramolecular charge-transfer. The enhancing and depressing effects were remarkable as the substituent was changed from electron-donating to electron-withdrawing groups. The path of the resonating delocalization was reversed in the case of the p-NO 2 group. To validate these results we effectively used Weinhold et al's natural bond orbital analysis to assess the UV and FT-IR spectrophotometric monitoring of the change reflected in this phenomenon when the substituent in the benzene ring is altered. The NBO analysis was simulated by ab inito computations at the HF/6-31G(d) level of theory, in order to properly detect any possible presence of a hydrogen bond association. The changes occurring in electron occupancies of double-centered bonds, antibonding orbitals and in lone-pair orbitals appraised the results, as did the s and p character listings of the twocentered bonds and the simultaneous changes occurring in the geometric parameters of the molecules in question. Contrary to its normal preference, in these molecules the nitrogen used sp 2 hybrid orbitals for its interaction, housing its electron lone-pair in the third p hybrid orbital. Furthermore, NBO analysis reflected the presence of a very soft intramolecular hydrogen association (C-H• • •), labelled by UV and FT-IR assignments, between the benzene and triazole rings in all Schiff bases but p-N(Me) 2. The n-* stabilization energy decreased in the order: p-OH > p-OCH 3 > p-Cl > p-CH 3 > H > p-NO 2 > o-OH. The relation between the band position and Hammett substitution constant is interpreted in relation to the molecular structure.
Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decre... more Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decreasing trend of the onset decomposition temperatures at which these compounds dissociated. The drop in the temperature was metal ion dependent; the sodium salt showed thermal stability up to 245 8C, whereas the complexes started their degradation processes at temperatures starting from 90 8C. While G* for the cleavage of the acetate moiety in the sodium salt was 63.76 kJmol K1 , it was 82.06 and 140.57 kJmol K1 in the cases of Ca 2C and Fe 3C , respectively. However, their complete fusion took place at 187.65, 150.34 and 98.77 8C, respectively, displaying a reversed trend which is probably indicative of some catalytic part on the binding metals. Using the Gaussian 98 W package of programs, ab initio molecular orbital treatments were applied to diclofenac and its Ca 2C and Fe 3C metal complexes to study their electronic structure at the atomic level. The thermochemistry of diclofenac sodium was followed through the TG fragmentation peak temperatures using the density functional theory calculations at the 6-31G(d) basis set level. The FT-IR data were in good agreement with the theoretically calculated values. Single point calculations at the B3LYP/ 6-311G(d) level of theory, were used to compare the geometric features, energies and dipole moments of these compounds to detect the effect of the binding metal ions on the thermal dissociation of their diclofenac complexes.
This work deals with a concise survey of some techniques that were used by different authors to d... more This work deals with a concise survey of some techniques that were used by different authors to determine experimentally the static dipole polarizability ranging from index of refraction measurements to optical, electrical or spectroscopic studies. A short discussion of the consequent ...
Journal of Pharmaceutical and Biomedical Analysis, Apr 1, 2005
The interactions between diclofenac (1), cetirizine (2) and ranitidine (3) were investigated by t... more The interactions between diclofenac (1), cetirizine (2) and ranitidine (3) were investigated by thermal analyses and UV, IR and (1)H NMR spectroscopic studies. In aqueous solution interaction occurred only between 1 and 2, yielding a high molecular weight (1:1), water insoluble ionic salt. Weak charge transfer (CT) interaction exists between the doubly charged piperazine moiety in 2, acting as an electron acceptor and (1). This CT interaction originates from the aromatic groups in 1. The CT band observed at approximately 315 nm exhibits very low absorbance as a result of the partial neutralization of the two positive charges present in the ionic salt. The IR bands of the mixture have wave numbers at nu 3323.1, 1695.3, and delta 1321.1-1210 cm(-1) indicating the presence of the NH group and the neutralized carbonyl group of 1, as well as the carboxylic group of 2. The 1,2,3-substitutions in the benzene ring of 1 in the mixture appear at 1161.1 cm(-1). The (1)H NMR of the mixed drugs shows singlet, triplet and multiplet proton signals due to the same effect.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Nov 1, 2006
Ab initio calculations, FT-IR and X-ray crystal analysis, indicated that the most stable configur... more Ab initio calculations, FT-IR and X-ray crystal analysis, indicated that the most stable configuration of 3-oxo-2-(phenylhydrazono)-3-(thien-2-yl)-propionitrile is the anti phenylhydrazone structure 1. Stability of such a conformation, over the possible E-form, 2, that would be stabilized by intramolecular hydrogen bonding, is due to interaction between electron-pair domains of the N, S and O atoms. However, the simulated and experimental IR frequency data indicated intermolecular hydrogen bonding between NH and CN, the latter being lowered to 2214 cm(-1). Studies on 3-oxo-3-phenyl-2-(phenylhydrazono)-propionitrile showed the same result, as well as, another intramolecular hydrogen association of the type N-H...O. This was clearly indicated by the absorbance of the carbonyl stretch at 1605 cm(-1). These data indicated the existence of a bifurcated hydrogen bond in 1a and a single intermolecular association in 1b.
To avoid the problem of basis set completeness and superposition error effects, various basis set... more To avoid the problem of basis set completeness and superposition error effects, various basis sets (including polarized and diffuse functions) have been implemented, at the Hartree-Fock and density functional levels of theory, to calculate the molecular static dipole polarizability and first dipole hyperpolarizability for the ground state of diclofenac sodium. Sophisticated ab initio methods did not favour the results. Comparison with the experimentally obtained value of the total molecular polarizability of diclofenac sodium indicated that the Hartree-Fock level of theory using the medium basis set 6-31G(d) extended with a p and d polarized functions was best suited for the description of such an electrical property. The total molecular static dipole polarizability was 429 m 3 as compared to the experimental value of 419 m 3 . The corresponding mean and anisotropy of the molecular dipole polarizability converged at 176.76 and 76.19 au, respectively. The intrinsic dipole moment was found to be 6.5571 D. The hyperpolarizability was studied theoretically applying the same selected basis sets and levels of theory as those chosen to calculate the polarizability. The mean hyperpolarizability, b, was found to be of almost the same value when using the medium basis set 6-31G(d) and the corresponding mildly extended basis set 6-31G(p,2d) at the HF level of theory. The incorporation of electron correlation effects, as in the DFT methods yielded exceedingly larger b values, increasing up to 1153 au. These high values are, probably, attributed to the charge-transfer existing between the phenyl rings within the molecular skeleton. The electronic charge distribution of the dic molecule is displayed by the NBO analysis of atomic charges calculated at the B3LYP/6-31G(d) level of theory.
This work deals with a concise survey of some techniques that were used by different authors to d... more This work deals with a concise survey of some techniques that were used by different authors to determine experimentally the static dipole polarizability ranging from index of refraction measurements to optical, electrical or spectroscopic studies. A short discussion of the consequent ...
The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity o... more The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity of this drug, was investigated by DFT calculations at the B3LYP/6-311G (d) level of theory. The repulsion forces, existing within the molecule because of the simultaneous presence of the acetate moiety as well as the two Cl atoms, created a twisted (748) diphenylamine structure to yield a preferred orientation. B3LYP/ 6-311G (d) calculations of diclofenac and its complexes, ML 2 (LZCa, Mg, Zn), showed that distortions of the geometric parameters were due to the differing hybridizations depending on the cation type in question. The energy gap values, DE, increased in the order MgOZnOCa, pointing out that the energy associated with electron pairing is greatest in the Mg 2C complex, due to the [Ne]3s 2 configuration and large charge to radius ratio (3.3) of the metal. The charge density contour plots of the complexes showed the negative charge as condensed around the N atom, indicating a very highly polarized M-N coordinate bond. Both the acid form and sodium salt displayed the typical weak N-H/O hydrogen bond association which is absent in the Mg, Ca and Zn complexes. The distance between H and O in all three (3.837 Mg, 3.307 Ca and 4.277 Zn Å) exceeded the possible limit of 3.0 Å .
Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decre... more Thermogravimetric analyses of diclofenac sodium, its Ca 2C and Fe 3C complexes manifested a decreasing trend of the onset decomposition temperatures at which these compounds dissociated. The drop in the temperature was metal ion dependent; the sodium salt showed thermal stability up to 245 8C, whereas the complexes started their degradation processes at temperatures starting from 90 8C. While G* for the cleavage of the acetate moiety in the sodium salt was 63.76 kJmol K1 , it was 82.06 and 140.57 kJmol K1 in the cases of Ca 2C and Fe 3C , respectively. However, their complete fusion took place at 187.65, 150.34 and 98.77 8C, respectively, displaying a reversed trend which is probably indicative of some catalytic part on the binding metals. Using the Gaussian 98 W package of programs, ab initio molecular orbital treatments were applied to diclofenac and its Ca 2C and Fe 3C metal complexes to study their electronic structure at the atomic level. The thermochemistry of diclofenac sodium was followed through the TG fragmentation peak temperatures using the density functional theory calculations at the 6-31G(d) basis set level. The FT-IR data were in good agreement with the theoretically calculated values. Single point calculations at the B3LYP/ 6-311G(d) level of theory, were used to compare the geometric features, energies and dipole moments of these compounds to detect the effect of the binding metal ions on the thermal dissociation of their diclofenac complexes.
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