Photoactive metallodrugs

Tuning the photoactivated anticancer activity of Pt(iv) compounds via distant ferrocene conjugation

“…The choice of the metal, its oxidation state, types and number of coordinated ligands and coordination geometry can all be used to tune photochemical and photobiological activity, an area of study still in its infancy. 5 Here we have modified a parent photochemotherapeutic agent, the octahedral diazido Pt( iv ) complex 1, by conjugation of an axial ligand to ferrocene as a light antenna with the aim of increasing the wavelength of activation (and increased light penetration into tissues) and introducing an additional mechanism of biological action based on redox reactions of ferrocene. In particular, we have carried out detailed DFT and TDDFT calculations on the conjugate Pt-Fe to investigate the effect of the heterobimetallic system on electronic transitions, and intersystem crossing to produce triplet states, and possible Pt( iv )–Fe( ii ) communication.…”

“…2,4 There is current interest in the design of the next generation of metal-based phototherapeutic agents on account of their unique photophysical and photochemical properties, especially potential for introducing novel mechanisms of anticancer activity to combat resistance to therapy with current drugs. [5][6][7][8] Metal complexes of Al(III), Zn(II), Ru(III), Pd(II), Sn(IV), and Lu(III) are either approved for clinical use or in clinical trials as photosensitisers for PDT. 2,5 Particularly notable is the current phase II clinical trial of the bipyridyl/phenanthroline Ru(III) complex TLD1433 for non-muscle-invasive bladder cancer.…”

“…[5][6][7][8] Metal complexes of Al(III), Zn(II), Ru(III), Pd(II), Sn(IV), and Lu(III) are either approved for clinical use or in clinical trials as photosensitisers for PDT. 2,5 Particularly notable is the current phase II clinical trial of the bipyridyl/phenanthroline Ru(III) complex TLD1433 for non-muscle-invasive bladder cancer. 9 The most widely used anticancer drug is cisplatin, cis-[PtCl 2 (NH 3 ) 2 ].…”

A Photodynamic and Photochemotherapeutic Platinum‐Iridium Charge‐Transfer Conjugate for Anticancer Therapy

“…Compared with traditional phototherapy based on organic molecules, photoactive metallodrugs show diverse structures with varied oxidation states, coordination numbers, and geometries, which offers potential novel mechanisms of action to circumvent drug resistance [1b,5] . Heterometallic complexes offer an efficient strategy to improve cytotoxicity since transition metal complexes exhibit metal‐specific anticancer mechanisms [6] .…”

Photoactivation of Boronic Acid Prodrugs via a Phenyl Radical Mechanism: Iridium(III) Anticancer Complex as an Example

“…Photoinduced prodrug activation is one of the most powerful strategies for cancer treatment with spatiotemporal resolution at the disease tissue. − In the literature, prodrugs based on metal complexes have been rapidly developed owing to their rich photochemical properties. , Indeed, prodrugs containing metal ions of platinum, − ruthenium, − and others − have been reported that can be either photocatalytically or photochemically activated within localized tumors. In view of the lower side effects for localized cancer treatment as in the clinical photodynamic therapy (PDT), there is a possibility of harnessing surrounding O 2 to aid prodrug activation, such as utilizing the type I photosensitizing mechanism by consuming reductants to photocatalytically reduce O 2 into superoxide radical anion (O 2 •– ) for boron-prodrug activation (Figure b). , However, tumors are known to feature a hypoxic microenvironment with an O 2 content of 0.02–2% .…”