Reactivity of arsenoplatin complex versus water and thiocyanate: a DFT benchmark study
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Reactivity of arsenoplatin complex versus water and thiocyanate: a DFT benchmark study Iogann Tolbatov1 · Cecilia Coletti1 · Alessandro Marrone1 · Nazzareno Re1 Received: 12 September 2020 / Accepted: 4 November 2020 © The Author(s) 2020
Abstract Seven different density functionals, including GGAs, meta-GGAs, hybrids and range-separated hybrids, and considering Grimme’s empirical dispersion correction (M06-L, M06-2X, PBE0, B3LYP, B3LYP-D3, CAM-B3LYP, ωB97X) have been tested for their performance in the prediction of molecular structures, energies and energy barriers for a class of newly developed antitumor platinum complexes involving main group heavy elements such as arsenic. The calculated structural parameters, energies and energy barriers have been compared to the available experimental data. The results show that range-separated hybrid functionals CAM-B3LYP and ωB97X give good results in predicting both geometrical parameters and isomerization energies and barrier heights and are promising new tools for the theoretical study of novel platinum(II) arsenic compounds. Keywords DFT · Benchmarking · Arsenoplatin · Platinum · Metal-based anticancer drugs
1 Introduction Since the discovery of the antitumor activity of cisplatin [1], transition metal complexes, an essential group of compounds in diverse fields of chemistry, have been gaining an increased importance in medicinal chemistry [2–5]. Most of the studies in bioinorganic chemistry have been devoted to the structure-based optimization of cisplatin or its analogs to gain more potent and less toxic anticancer drugs [6–8]. The well-known toxicity of cisplatin is seemingly ascribed to the facile in vivo substitution of the chloride ligands by endogenous targets. Indeed, their replacement with less reactive chelate ligands in carboplatin and oxaliplatin has successfully yielded compounds with a higher therapeutic index [9–12]. Another major hurdle for the use of platinum compounds in cancer treatment is due to the intrinsic and acquired Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00214-020-02694-w) contains supplementary material, which is available to authorized users. * Nazzareno Re [email protected] 1
Dipartimento di Farmacia, Università “G d’Annunzio” di Chieti-Pescara, Via dei Vestini 31, Chieti, Italy
resistance to this class of drugs. Several innovative strategies have been developed to overcome this issue, such as the design of new types of platinum complexes like trans Pt(II) compounds, polynuclear Pt(II) compounds, Pt(IV) prodrugs or new nanomolecular or nanoparticle drug delivery approaches. Inspired by the identification of a new Pt-As bond in a nanoparticulate delivery system for loading arsenic trioxide (As2O3)—an inorganic compound with a wellknown anticancer activity—and cisplatin, a new complex Cl–Pt(NH = C(CH3)–O)2As(OH)2, arsenoplatin (AP), has been recently developed showing a promising anticancer activity in drug-resistant cell lines. Indeed, arsenoplatin, an add
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