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Photocatalytic cancer therapy (PCT) has emerged as a cutting-edge anticancer mechanism of action, harnessing light energy to mediate the catalytic oxidation of intracellular substrates. PCT is of significant current importance due to its potential to address the limitations of conventional chemotherapy, particularly drug resistance and side effects. This approach offers a noninvasive, targeted cancer treatment option by utilizing metal-based photocatalysts to induce redox and metabolic disorders within cancer cells. The photocatalysts disrupt the cancer cell metabolism by converting NADH/NAD(P)H to NAD⁺/NAD(P)⁺ via catalytic photoredox processes, altering intracellular NAD⁺/NADH or NAD(P)⁺/NAD(P)H ratios, which are crucial for cellular metabolism. Ir(III), Ru(II), Re(I), and Os(II) photocatalysts demonstrated promising PCT efficacy. Despite these developments, gaps remain in the literature for translating this new anticancer mechanism into clinical trials. This Perspective critically examines the developments in this research area and provides future directions for designing efficient photocatalysts for PCT. Show less

The preparation of a new series of Ir(III) tetrazolato complexes with the general formula [Ir(C^N)2(N^N)]0/+, where the ancillary ligand (N^N) is represented in turn by 2-pyridyltetrazolato (PTZ-), 2-pyrazinyltetrazolato (PYZ-) or 2-pyridyl 5-trifluoromethyl tetrazolato (PTZ-CF3-), is described herein. The design of the cyclometalated (C^N) ligands, namely 2-phenylisonicotinonitrile (ppyCN) and 2-(2,4-difluorophenyl)isonicotinonitrile (F2ppy-CN), features the well-known ppy- or F2ppy core, with the introduction of one electron-withdrawing cyano (-CN) group at the para position of the pyridyl ring. The photophysical and electrochemical properties of the new Ir(III) cyclometalated complexes have been investigated and the resulting data suggest how the (C^N) ligands significantly rule the luminescence behavior of the new complexes. Further blue or red shifting of the emission profiles of the neutral complexes was observed upon their conversion into cationic species through the regioselective addition of a methyl moiety to the coordinated tetrazolato ring. Lastly, neutral [Ir(F2ppy-CN)2(PTZ)] was used as an emissive phosphor for the fabrication of an OLED-type device. Show less

Bioisosteres are a useful approach to address pharmacokinetic liabilities and improve drug-like properties. Specific to developing metalloenzyme inhibitors, metal-binding pharmacophores (MBPs) have been combined with bioisosteres, to produce metal-binding isosteres (MBIs) as alternative scaffolds for use in fragment-based drug discovery (FBDD). Picolinic acid MBIs have been reported and evaluated for their metal-binding ability, pharmacokinetic properties, and enzyme inhibitory activity. However, their structural, electronic, and spectroscopic properties with metal ions other than Zn(II) have not been reported, which might reveal similarities and differences between MBIs and the parent MBPs. To this end, [M(TPA)(MBI)]⁺ (M = Ni(II) and Co(II), TPA = tris(2-pyridylmethyl)amine) is presented as a bioinorganic model system for investigating picolinic acid, four heterocyclic MBIs, and 2,2'-bipyridine. These complexes were characterized by X-ray crystallography as well as NMR, IR, and UV-vis spectroscopies, and their magnetic moments were accessed. In addition, [(Tp^Ph,Me)Co(MBI)] (Tp^Ph,Me = hydrotris(3,5-phenylmethylpyrazolyl)borate) was used as a second model compound, and the limitations and attributes of the two model systems are discussed. These results demonstrate that bioinorganic model complexes are versatile tools for metalloenzyme inhibitor design and can provide insights into the broader use of MBIs. Show less