Conformational and vibrational study of platinum(II) anticancer drugs: cis-diamminedichloroplatinum (II) as a case study

Abstract

A conformational and vibrational analysis of cisplatin ͓cis-diamminedichloro-platinum͑II͔͒ ͑cDDP͒ is reported. Several theory methods ͑from Hartree-Fock to Møller-Plesset and density functional theory͒ combined with different all-electron basis sets are evaluated, in view of determining the best suited strategy for accurately representing this molecule. This choice is based on the best compromise between accuracy and computational requirements. Different scaling models of the cDDP vibrational modes were tested for obtaining the best scaling factors to be used in this type of inorganic systems. The structural parameters and vibrational results predicted by the calculations are compared with the corresponding experimental data, namely, x-ray structure, and Raman and inelastic neutron scattering spectra. Finally, a complete assignment of the cDDP vibrational spectra is presented.

A molecular view of cisplatin's mode of action: interplay with DNA bases and acquired resistance

“…These results were interpreted in the light of the full conformational analysis previously performed by the authors for cisplatin [21][22][23]25,26 and the purine bases adenine 28 and guanine, 27 as well as for the optimized structures presently obtained for reduced glutathione (Fig. 2), [cDDP-A 2 ] and [cDDP-G 2 ] (Fig.…”

“…Different scaling factors were applied to distinct frequency sets: adapted from Merrick and co-workers 53 for the organic moieties of the adducts (0.9513 and 0.9846 below and above 700 cm À1 , respectively); and the parameters developed by Amado et al 22 , d NPtN )). This was considered a valid approach since the vibrational transition energies of the adenine and guanine ligands are well separated from those involving the metal (i.e.…”

“…The data obtained along this study were interpreted on the basis of the extensive theoretical and experimental work available for these systems, 13,[17][18][19][20] including previous data gathered by the authors (by vibrational spectroscopy and theoretical calculations) for cisplatin and cisplatin-like agents, [21][22][23][24][25][26] as well as for guanine, 27 adenine 28 and glutathione. The detailed knowledge of the molecular basis of the cDDP-guanine/adenine and cDDPglutathione interplay gathered in this work will pave the way for future studies on other platinum and palladium-based agents previously characterized by the authors and assessed as to their cytotoxicity towards several human cancer cell lines.…”

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy

“…The results obtained along this work were related with a thorough conformational analysis of the newly synthesised metal-based agents (by Raman, IR and INS coupled to theoretical approaches) [18][19][20][21][22][23][24][34][35][36] and with biological assays for the evaluation of cytotoxicity performed alongside on the same systems -cell growth and viability inhibition, as well as anti-angiogenic and anti-metastatic abilities [14][15][16]27,[40][41][42][43]45 -allowing us to establish a reliable correlation between structural/ conformational features, cytotoxic activity and impact on cellular metabolism. This data, coupled to previous INS and EXAFS studies on drug-DNA adducts (carried out at ISIS and DLS 18,21,23,24 ), will pave the way for future work on other promising cisplatin-like anticancer agents (both Pt(II) and Pd(II)) which have been studied by the team in the last few years, as well as on distinct human cancer cells.…”

Correct Modeling of Cisplatin: a Paradigmatic Case

“…The vibrational spectra of cisplatin have been the object of several experimental studies,5, 6, 7 whereas its high‐resolution crystal structure has been reported only some years ago 8. Besides experimental studies, several investigations have focused on the theoretical prediction of its structure and vibrational frequencies 6, 7, 9, 10.…”