Benzothiazole‐Based Cycloplatinated Chromophores: Synthetic, Optical, and Biological Studies

Cycloplatinated complexes based on 2‐(4‐substituted)benzothiazole ligands of type [Pt(R‐PBT‐κC,N)Cl(L)] (PBT=2‐phenylbenzothiazole; R=Br (1), Me2N (2); L=dimethyl sulfoxide (DMSO; a), 1,3,5‐ triaza‐7‐phosphaadamantane (PTA; b), triphenylphosphine 3,3′,3′′‐trisulfonate (TPPTS; c)) and [Pt(Br‐PBT‐κC)Cl(PTA)2] (3) are presented. On the basis of the photophysical data and time‐dependent (TD)‐DFT calculations (1 a and 2 a), the low‐lying transitions (absorption and emission) were associated with ligand‐center (LC) charge transfer, with minor metal‐to‐ligand charge transfer (MLCT), and intraligand charge transfer (ILCT) [Me2N‐PBT→PBT] excited states, respectively. Simultaneous fluorescence/phosphorescence bands were found in fluid solutions (and also in the solid state for 2 a), which become dominated by triplet emission bands in rigid media at 77 K. The effect of the concentration on emissive behavior of 2 a, b indicated the occurrence of aggregation‐induced luminescence properties related to the occurrence of metal–metal and π⋅⋅⋅π interactions, which are more enhanced in 2 a because of the less bulky DMSO ligand. The behavior of 2 a toward para‐toluenesulfonic acid (PTSA) in aerated acetonitrile and to hydrogen chloride gas in the solid state has been evaluated, thus showing a clear reversible change between the 1ILCT and 3LC/3MLCT states due to protonation of the NMe2 group (theoretical calculations on 2 a‐H+). Solid 2 a undergoes a surprising oxidation of the PtII center to PtIV with concomitant deoxygenation of DMSO, under prolonged reaction with hydrogen chloride gas to afford the PtIV/dimethyl sulfide complex (mer‐[Pt(Me2N‐PBT‐κC,N)Cl3(SMe2)]; mer‐4), which evolves in solution to fac‐4, as confirmed by X‐ray studies. Cytotoxic activity studies on A549 and HeLa cell lines indicated cytotoxic activity of 1 b and 2 a, b. In addition, fluorescent cell microscopy revealed cytoplasmic staining, more visible in perinuclear areas. Inhibition of tubulin polymerization by 1 b in both cells is presented as a preliminary mechanism of its cytotoxic action. Benzothiazole on Pt: The optical properties and biological activities of two series of cycloplatinated complexes featuring 2‐arylbenzothiazole are presented. A complex series of reactions of [Pt(Me2N‐PBT)Cl(DMSO)] (DMSO=dimethyl sulfoxide, PBT=2‐phenylbenzothiazole) with hydrogen chloride gas in the solid state results in the unexpected formation of a PtIV/dimethyl sulfide complex. Inhibition of tubulin polymerizati