Pt NMR parameters as strong descriptors in one-parameter QSAR models for platinum-based antitumor compounds.

Highly predictive one-parameter quantitative structure-activity relationship models have been developed for platinum-based anticancer drugs using the Pt NMR parameters as strong descriptors. The developed quantitative structure-activity relationship models were applied in diverse homogeneous sets of antiproliferative Pt(II) and Pt(IV) compounds. These observations form the basis for making predictions of cytotoxicity for a broad range of platinum-based antitumor compounds just from inspection of calculated or experimentally determined Pt NMR parameters.

Prediction of Pt NMR of photoactivable diazido- and azine-Pt(IV) anticancer agents by DFT computational protocols.

Pt NMR chemical shifts for a series of large-sized photoactivable anticancer diazido-Pt(IV), homopiperizine-Pt(IV) and multifunctional azine-Pt(IV) complexes hardly to be probed experimentally and by sophisticated four-component and two-component relativistic calculations are predicted with high accuracy by density functional theory computational protocols. The calculated Pt NMR chemical shifts constitute a crucial descriptor for making highly predictive one-parameter quantitative structure activity relationships models that help in designing photoactivable Pt(IV)-based antitumor agents with high cytotoxicity and selectivity. Copyright © 2016 John Wiley & Sons, Ltd.

Prediction of (195) Pt NMR chemical shifts of dissolution products of H2 [Pt(OH)6 ] in nitric acid solutions by DFT methods: how important are the counter-ion effects?

(195) Pt NMR chemical shifts of octahedral Pt(IV) complexes with general formula [Pt(NO3 )n (OH)6 - n ](2-) , [Pt(NO3 )n (OH2 )6 - n ](4 - n) (n = 1-6), and [Pt(NO3 )6 - n  - m (OH)m (OH2 )n ](-2 + n - m) formed by dissolution of platinic acid, H2 [Pt(OH)6 ], in aqueous nitric acid solutions are calculated employing density functional theory methods. Particularly, the gauge-including atomic orbitals (GIAO)-PBE0/segmented all-electron relativistically contracted-zeroth-order regular approximation (SARC-ZORA)(Pt) ∪ 6-31G(d,p)(E)/Polarizable Continuum Model computational protocol performs the best. Excellent second-order polynomial plots of δcalcd ((195) Pt) versus δexptl ((195) Pt) chemical shifts and δcalcd ((195) Pt) versus the natural atomic charge QPt are obtained.

Accurate prediction of 195Pt NMR chemical shifts for a series of Pt(II) and Pt(IV) antitumor agents by a non-relativistic DFT computational protocol.

The GIAO-PBE0/SARC-ZORA(Pt)∪6-31+G(d)(E) (E = main group element) computational protocol without including relativistic and spin-orbit effects is offered here for the accurate prediction of the (195)Pt NMR chemical shifts of a series of cis-(amine)2PtX2 (X = Cl, Br, I) anticancer agents (in total 42 complexes) and cis-diacetylbis(amine)platinum(II) complexes (in total 12) in solutions employing the Polarizable Continuum Model (PCM) solvation model, thus contributing to the difficult task of computation of (195)Pt NMR. Calculations of the torsional energy curves along the diabatic (unrelaxed) rotation around the Pt-N bond of the cis-(amine)2PtX2 (X = Cl, Br, I) anticancer agents revealed the high sensitivity of the (195)Pt NMR chemical shifts to conformational changes. The crucial effect of the conformational preferences on the electron density of the Pt central atom and consequently on the calculated δ(195)Pt chemical shifts was also corroborated by the excellent linear plots of δ(calcd)((195)Pt) chemical shifts vs.