The role of the basis set and the level of quantum mechanical theory in the prediction of the structure and reactivity of cisplatin

Abstract

In this article, we conducted an extensive ab initio study on the importance of the level of theory and the basis set for theoretical predictions of the structure and reactivity of cisplatin [cis‐diamminedichloroplatinum(II) (cDDP)]. Initially, the role of the basis set for the Pt atom was assessed using 24 different basis sets, including three all‐electron basis sets (ABS). In addition, a modified all‐electron double zeta polarized basis set (mDZP) was proposed by adding a set of diffuse d functions onto the existing DZP basis set. The energy barrier and the rate constant for the first chloride/water exchange ligand process, namely, the aquation reaction, were taken as benchmarks for which reliable experimental data are available. At the B3LYP/mDZP/6‐31+G(d) level (the first basis set is for Pt and the last set is for all of the light atoms), the energy barrier was 22.8 kcal mol−1, which is in agreement with the average experimental value, 22.9 ± 0.4 kcal mol−1. For the other accessible ABS (DZP and ADZP), the corresponding values were 15.4 and 24.5 kcal mol−1, respectively. The ADZP and mDZP are notably similar, raising the importance of diffuse d functions for the prediction of the kinetic properties of cDDP. In this article, we also analyze the ligand basis set and the level of theory effects by considering 36 basis sets at distinct levels of theory, namely, Hartree‐Fock, MP2, and several DFT functionals. From a survey of the data, we recommend the mPW1PW91/mDZP/6‐31+G(d) or B3PW91/mDZP/6‐31+G(d) levels to describe the structure and reactivity of cDDP and its small derivatives. Conversely, for large molecules containing a cisplatin motif (for example, the cDDP‐DNA complex), the lower levels B3LYP/LANL2DZ/6‐31+G(d) and B3LYP/SBKJC‐VDZ/6‐31+G(d) are suggested. At these levels of theory, the predicted energy barrier was 26.0 and 25.9 kcal mol−1, respectively, which is only 13% higher than the actual value. © 2012 Wiley Periodicals, Inc.

Conformational insights and vibrational study of a promising anticancer agent: the role of the ligand in Pd(ii)–amine complexes

“…In order to further improve the representation of this type of Pd(II)-amine complex, it is of paramount importance to develop new basis sets as recently undertaken for Pt(II) complexes 19,42 (which was beyond the scope of this work). At the moment, it seems that the precise estimate of one type of metal-ligand bond length leads to uncertainty in the other one, and an improvement of the bond lengths results in a worse description of the bond angles.…”

“…In this study, quantum mechanical calculations were carried out for Pd 2 -Spm at the DFT level, since this approach has been shown to deliver accurate results for this type of system. [17][18][19] A theoretical model previously reported by the authors for a mononuclear Pd(II) compound bearing non-chelating ligands 17 was presently evaluated because of its suitability for the highly flexible polynuclear polydentate chelate Pd 2 -Spm. The accuracy of the calculated results was assessed by comparison with the experimental data available on this chelate -both studies reported X-ray structural information 14 and the vibrational results gathered in this work.…”

Platinum(II) and palladium(II) aryl-thiosemicarbazone complexes: synthesis, characterization, molecular modeling, cytotoxicity, and antimicrobial activity

“…The geometries for the cis and trans isomers were optimized in the gas phase at the B3LYP level [24] with the 6-31+G(d) basis set used for hydrogen and heavy elements, except for the metal for which the LanL2DZ [25] effective core potential was set for core electrons with its balanced double-zeta basis set for valence electrons [26]. This calculation scheme is abbreviated as B3LYP/LanL2DZ/6-31+G(d) and was recently evaluated for cisplatin reactivity [27]. The same level of theory was used for vibrational frequency calculation in order to characterize the structures as true minima on the potential energy surface (all harmonic frequencies real) as well as to analyze the vibrational normal modes.…”

The conformation effect of the diamine bridge on the stability of dinuclear platinum(II) complexes and their hydrolysis

“…2. In order to assess most of DFT approaches and basis sets to predict hydrolysis energy barrier for Pt(II) complexes, please refer to the reference [34]. The transition states (TS) were assembled for all conformations aiming to assess the conformational role on the reaction rate.…”