195 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 195 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 195 Pt NMR parameters. Copyright © 2016 John Wiley & Sons, Ltd.

Prediction of 195 Pt NMR of photoactivable diazido- and azine-Pt(IV) anticancer agents by DFT computational protocols.

195 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 195 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. Despite of neglecting relativistic and spin orbit effects the good agreement of the calculated δ (195) Pt chemical shifts with experimental values is probably because of the fact that the contribution of relativistic and spin orbit effects to computed σ(iso) (195) Pt magnetic shielding of Pt(IV) coordination compounds is effectively cancelled in the computed δ (195) Pt chemical shifts, because the relativistic corrections are expected to be similar in the complexes and the proper reference standard used. To probe the counter-ion effects on the (195) Pt NMR chemical shifts of the anionic [Pt(NO3 )n (OH)6 - n ](2-) and cationic [Pt(NO3 )n (OH2 )6 - n ](4 - n) (n = 0-3) complexes we calculated the (195) Pt NMR chemical shifts of the neutral (PyH)2 [Pt(NO3 )n (OH)6 - n ] (n = 1-6; PyH = pyridinium cation, C5 H5 NH(+) ) and [Pt(NO3 )n (H2 O)6 - n ](NO3 )4 - n (n = 0-3) complexes. Counter-anion effects are very important for the accurate prediction of the (195) Pt NMR chemical shifts of the cationic [Pt(NO3 )n (OH2 )6 - n ](4 - n) complexes, while counter-cation effects are less important for the anionic [Pt(NO3 )n (OH)6 - n ](2-) complexes. The simple computational protocol is easily implemented even by synthetic chemists in platinum coordination chemistry that dispose limited software availability, or locally existing routines and knowhow. Copyright © 2016 John Wiley & Sons, Ltd.

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. the natural atomic charge Q(Pt). Furthermore, for the accurate prediction of the (195)Pt NMR chemical shifts of the cis-bis(amine)Pt(II) anticancer agents bearing carboxylato- as the leaving ligands (in total 8) and a series of octahedral Pt(IV) antitumor agents (in total 20 complexes) the non-relativistic GIAO-PBE0/SARC-ZORA(Pt)∪6-31+G(d)(E) computational protocol performs best in combination with the universal continuum solvation model based on solute electron density called SMD for aqueous solutions. Despite neglecting relativistic and spin orbit effects the agreement of the calculated δ(195)Pt chemical shifts with experimental values is surprising probably due to effective error compensation. Moreover, the observed solvent effects on the structural parameters of the complexes probably overcome the relativistic effects, and therefore the successful applicability of the non-relativistic GIAO-PBE0/SARC-ZORA(Pt)∪6-31+G(d)(E) computational protocol in producing reliable δ(calcd)((195)Pt) chemical shifts could be understood. In a few cases (e.g. the dihydroxo Pt(IV) complexes) the higher deviations of the calculated from the experimental values of δ(195)Pt chemical shifts are probably due to the fact that the experimental assignments refer to a different composition of the complexes in solutions than that used in the calculations, and different hydrogen bonding and formation of dimeric species.