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

Abstract

Cycloplatinated complexes based on 2-(4-substituted)benzothiazole ligands of type [Pt(R-PBT-κC,N)Cl(L)] (PBT=2-phenylbenzothiazole; R=Br (1), Me N (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) ] (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) [Me N-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 ILCT and LC/ MLCT states due to protonation of the NMe group (theoretical calculations on 2 a-H ). Solid 2 a undergoes a surprising oxidation of the Pt center to Pt with concomitant deoxygenation of DMSO, under prolonged reaction with hydrogen chloride gas to afford the Pt /dimethyl sulfide complex (mer-[Pt(Me N-PBT-κC,N)Cl (SMe )]; 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.

Design of Luminescent, Heteroleptic, Cyclometalated PtII and PtIV Complexes: Photophysics and Effects of the Cyclometalated Ligands

“…However, in the thienylpyridine derivative 1 f , it is the sulfur atom instead of the H−C proton of the thiazoline ring that is oriented toward the Pt center. The Pt⋅⋅⋅S distance (3.15 Å) is shorter than the van der Waals limit (3.55 Å) and comparable to those reported in trans ‐[Pt(Br‐pbt‐κC)Cl(PTA) 2 ] (3.073 Å; PTA=1,3,5‐ triaza‐7‐phosphaadamantane) or in the penta‐coordinated cation [Pt(ppy)(9S3)] + [2.9518(17) Å, 9S3=1,4,7‐trithiacyclononane] . In the crystals, a certain degree of π stacking involving the bzq and oxd ligands was observed for 1 a , whereas only offset secondary interactions were found in 1 d and 1 f (Figures S5–S7, Supporting Information).…”

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

“…Only platinum derivative has emerged as an effective inductor of apoptotic death on HepG2 and MCF-7 cells and caused cell cycle arrest at G0/G1 phase while palladium was inactive. On the other hand, the inclusion of 2-(4-substituted)benzothiazoles (compound 18 in Figure 5) as ligands resulted in potent cytotoxic agents through tubulin polymerization in A549 and HeLa cell lines [51].…”

Heterobimetallic PtII‐AuI Complexes Comprising Unsymmetrical 1,1‐Bis(diphenylphosphanyl)methane Bridges: Synthesis, Photophysical, and Cytotoxic Studies

“…Besides, ease thermal access to non‐emissive metal centered d‐d excited states and also direct solvent interactions should not be ruled out. [17a], …”

“…In recent years, cycloplatinated(II) complexes have also attracted growing attention for their possible use as anticancer drugs and the results are quite promising . These complexes, possess strong σ(Pt–C) bonds what increases their stability in physiological conditions, avoiding off‐target reactions, and, therefore, simplifies the potential therapeutic applications . Additionally, recent studies have also demonstrated that the antiproliferative properties of some of these platinum complexes improved upon attaching a second Au I unit to the organometallic Pt compound .…”