DFT study of the molecular and crystal structure and vibrational analysis of cisplatin.

DFT and periodic-DFT (PAW-PBE method, code VASP) calculations have been performed to study the structural and vibrational characteristics of cis-diamminedichloroplatinum(II) (cisplatin) at molecular and outside molecular level. To estimate the effect of the intermolecular interactions in crystal on the structural and vibrational properties of cisplatin, three theoretical models are considered in the present study: monomer (isolated molecule), hydrogen bonded dimer and periodic solid state structures. The work focused on the role of the theoretical models for correct modeling and prediction of geometrical and vibrational parameters of cisplatin. It has been found that the elaborate three-dimensional intermolecular hydrogen bonding network in the crystalline cisplatin significantly influences the structural and vibrational pattern of cisplatin and therefore the isolated cisplatin molecule is not the correct computational model regardless of the theoretical level used. To account for the whole intermolecular hydrogen bonding network in direction of both a and c axis and for more reliable calculations of structural and vibrational parameters periodic DFT calculations were carried out in the full crystalline periodic environment with the known lattice parameters for each cisplatin polymorph phase. The model calculations performed both at molecular level and for the periodic structures of alpha and beta cisplatin polymorph forms revealed the decisive role of the extended theoretical model for reliable prediction of the structural and vibrational characteristics of cisplatin. The powder diffraction pattern and the calculated IR and Raman spectra predicted beta polymorph form of our cisplatin sample freshly synthesized for the purposes of the present study using the Dhara's method. The various rotamers realized in the polymorph forms of cisplatin were explained by the low population of the large number of rotamers in solution as well as with the high rotamer interconversion rate due to the low energy barrier.

Effect of platinum (II) complexes of 4-methoxy- and 4-chlorobenzoic acid hydrazides on Saccharomyces cerevisiae.

This study reports the anti-yeast effect of the 4-methoxybenzoic acid hydrazide (pmbah), 4-chlorobenzoic acid hydrazide (pcbah) and their Pt(II) complexes: cis- [PtL2X2] and cis- [PtL(NH3)Cl2] where L is either pcbah or pmbah and X is Cl, Br or I. MICs of the 4- substituted analogues (20,000-625 microM) are much lower than those of the previously reported benzoic acid hydrazide and 3-methoxybenzoic acid hydrazide. Complex formation results in significant increase of potency which may be due to a change in the mechanism of action, but the MIC (> 400-50 microM) and the IC50 (> 400-1 microM) values show that higher activity of the ligands in the free state does not result in enhanced complex activity. Differences in the potency of iodo-, chloro- and bromo complexes suggest MIC and IC50 values may be in correlation with the stability of the complex, rather than with the activity of the free ligands. Osmotically unstable mutants were more susceptible to the compounds than their parent strains, but differences among the parent strains, but differences among the parent strains were greater.

Platinum(II) complexes of 4-methoxy- and 4-chlorobenzoic acid hydrazides. Synthesis, characterization, and cytotoxic effect.

The complexes [Pt(NH3)(pmbah)Cl2], [Pt(NH3)(pcbah)Cl2], [Pt(pmbah)2X2] and [Pt(pcbah)2X2] (pmbah = 4-methoxybenzoic acid hydrazide, pcbah = 4-chlorobenzoic acid hydrazide; X = Cl, Br, I) have been synthesized and characterized by elemental analysis, electric conductivity, 1H NMR, IR, and electronic spectra. A cis-square planar structure with hydrazide ligands coordinated via the NH2 groups has been proposed for these compounds. The complexes, but not the free ligands, have shown a strong growth inhibitory effect in Friend leukemia cells in vitro, most of which are more active than cisplatin.

Effect of platinum(II) complexes of benzoic and 3-methoxybenzoic acid hydrazides on Saccharomyces cerevisiae.

The inhibitory effect of benzoic acid hydrazide (bah) and 3-methoxybenzoic acid hydrazide (mbah) on Saccharomyces cerevisiae strains has been compared to that of their platinum(II) complexes: cis-[Pt(mbah)2X2], cis-[Pt(NH3)(mbah)Cl2].0.5 H2O, cis-[Pt(mbah)2X2] and cis[Pt(NH3)(mbah)Cl2] (mean = Cl, Br = I), and cis-[Pt(NH3)2Cl2]. The minimal inhibitory concentrations for bah and mbah were 5000-20,000 microM whereas for their Pt(II) complexes they were much less (25-800 microM) and did not exceed these of cisplatin (100-800 microM). The activity of the Pt(II) complexes of bah and mbah varied in wide ranges for the different yeast strains tested. Osmotically unstable mutants were found to be more susceptible. The most active complexes were [Pt(NH3)(bah)Cl2].0.5 H2O and [Pt(NH3)(mbah)Cl2].

Platinum (II) complexes of benzoic- and 3-methoxybenzoic acid hydrazides. Synthesis, characterization, and cytotoxic effect.

The complexes [Pt(bah)2X2], [Pt(NH3)(bah)Cl2].0.5H2O, [Pt(mbah)2X2], and [Pt(NH3)(mbah)Cl2] (bah = benzoic acid hydrazide, mbah = 3-methoxybenzoic acid hydrazide; X = Cl, Br, I) have been prepared and characterized by elemental analysis, electric conductivity, IR, 1H NMR, and electronic spectra. A cis-square planar structure with hydrazide ligands coordinated via the NH2-groups has been proposed for these complexes. The complexes have shown a growth-inhibitory effect against Friend leukemia cells in culture comparable to that of the antitumor drug cisplatin.

Platinum(II), platinum(IV), and palladium (II) complexes of amino substituted phosphine oxides: synthesis, characterization, and antitumor activity.

The complexes [Pt(dapo)2Cl2], [PtNH3(dapo)Cl2], [Pt(py)(dapo)Cl2], [Pt(mbpo)Cl2].H2O, [Pt(mbpo)(OH)2Cl2].H2O, [Pd(dapo)2Cl2], and [Pd(mbpo)Cl2], where dapo is dimethyl aminomethylphosphine oxide and mbpo is methyl bis(aminomethyl)phosphite oxide have been synthesized and characterized by elemental analyses, electric conductivity, infrared, 1H NMR and electronic spectra. The ligands are found to be coordinated only via the amino groups. The complexes are of cis-square planar configuration with the exception of [Pt(mbpo)(OH)2Cl2].H2O which is pseudo-octahedral. An in vivo antitumor screening of the complexes against Leukemia L1210 was performed. A considerable activity (T/C = 233%) was observed for [PtNH3(dapo)Cl2]. The activity of the remaining complexes was below the accepted criterion.