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Hydrolytically stable PdII and PtII complexes supported by acyclic diaminocarbene ligands represent a novel class of structural organometallic anticancer agents exhibiting nanomolar antiproliferative activity in a panel of cancer cell lines (IC50 0.07–0.81 μM) and up to 300‐fold selectivity for cancer cells over normal primary fibroblasts. The lead drug candidate was 300 times more potent than cisplatin in vitro and showed higher efficacy in reducing the growth of aggressive MDA‐MB‐231 xenograft tumors in mice. [ABSTRACT FROM AUTHOR]

2-R-2 H-Tetrazol-5-ylacetic acids (abbreviated as 2-R-taa; R = Me, iPr, tBu) react with K2[PtCl4] in 1 m HCl in H2O at r.t. furnishing trans-platinum(II) complexes trans-[PtCl2(2-R-taa)2] ( 1- 3), whereas cis-isomeric species cis-[PtCl2(2-R-taa)2] (R = iPr, 4; tBu, 5) are isolated at lower temperature (4-6 °C). In the presence of EtOH in the reaction mixture, esterification of the tetrazol-5-ylacetoxy group of 2- tBu-taa leads to trans-[PtCl2(ethyl 2- tert-butyl-2 H-tetrazol-5-ylacetate)2] ( 6). Complexes 1- 6 were characterized by elemental analyses (CHN), HRESI+-MS, 1H, 13C{1H}, 195Pt{1H} NMR and IR spectroscopy, differential scanning calorimetry/thermogravimetry (DSC/TG), and X-ray diffraction (for 1·H2O, 2, 3·2H2O, 4, 5·2H2O, and 6). The generation of the tetrazole-based complexes in solution (1 m DCl in D2O, 25 °C) was studied by 1H NMR spectroscopy and HPLC-MS. The obtained data indicate the initial formation of anionic [PtCl3(2-R-taa)]- complexes that are subsequently converted into disubstituted isomeric platinum(II) species cis- and trans-[PtCl2(2-R-taa)2]. By contrast to cis- and trans-[PtCl2(2-R-taa)2] that were inactive in two human cancer models in vitro (IC50 > 100 µ m), complex 6 demonstrated noticeable antiproliferative effects in HT-29 colon and MCF-7 breast carcinoma cell lines with IC50 values of 14.2 ± 1.1 and 5.8 ± 1.2 µ m, respectively. [ABSTRACT FROM AUTHOR]

Abstract A synthesis of the PdII and PtII N , N -diaryldiazabutadiene complexes and their self-assembly into infinite 1-dimensional chains in the solid state via rare C (sp2)–H ... Hal hydrogen bonding is reported. All the new compounds were characterized using elemental analyses (C, H, N), ESI-MS, IR, 1H and 13C NMR techniques and X-ray diffraction analysis. The nature and energies of intermolecular non-covalent interactions, which are responsible for the supramolecular polymerization, were studied theoretically using DFT calculations and topological analysis of the electron density distribution within the formalism of Bader's theory (QTAIM method). While chloro-complexes, which feature a relatively stronger C (sp2)–H ... Hal hydrogen bonding, form supramolecular polymers, the iodo-derivative does not self-assemble into 1-D chains due to the dominance of other crystal packing forces over the potential H⋯I contacts. Thus, the C (sp2)–H ... Hal HB can dictate a packing preference in the solid state and serve as a useful tool for supramolecular engineers. Graphical abstract Image 1 Highlights • Synthesis of the new PdII and PtII N , N -diaryldiazabutadiene complexes. • Self-assembly of the new complexes into 1-dimensional chains in the solid state via C (sp2)–H ... Hal hydrogen bonding. • X-ray diffraction analysis of the new materials. • Theoretical study of the nature and energies of intermolecular non-covalent interactions. [ABSTRACT FROM AUTHOR]