Potent Photochemotherapeutic Activity of Iron(III) Complexes on Visible Light-induced Ligand to Metal Charge Transfer

Iron(III) Complex-Functionalized Gold Nanocomposite as a Strategic Tool for Targeted Photochemotherapy in Red Light

“…The phenolate/carboxylate-based tetradentate ligand bis­(3,5 di- tert -butyl-2-hydroxybenzyl)­glycine (L 1 ) and 1,10 phenanthroline-based linker ligand 5-(1,2-dithiolan-3-yl)- N -(1,10-phenanthroline-5-yl)­pentanamide (L 2 ) were synthesized as per previously published reports and characterized using high-performance liquid chromatography (HPLC), FT-IR spectroscopy, 1 H and 13 C NMR, and Q-TOF-ESI mass spectroscopy before complexation with iron­(III) (Figures S1–S10). , Complex 1 of molecular formula [Fe­(L 1 )­(L 2 )] (Scheme ) was prepared by addition of a methanolic solution of L 1 followed by the addition of a methanolic solution of L 2 to a methanolic solution of Fe­(NO 3 )·9H 2 O under a N 2 condition at room temperature (RT) with continuous stirring for 2 h. A pure microcrystalline solid of complex 1 was obtained after precipitation with diethyl ether. Elemental analysis correlated with the proposed structure of the complex and determined the purity of the isolated, microcrystalline solid of complex 1 .…”

“…Phenolate carboxylate-based tetradentate ligand, L 1 , and 1,10-phenanthroline-based ligand, L 2 , were synthesized as per previously published protocols, , followed by characterization by FT-IR, 1 H and 13 C NMR, and Q-TOF-ESI mass spectra before complexation. Gold nanoparticles (AuNPs) were synthesized by the sodium citrate reduction method as per a published report …”

“…TD-DFT calculations also predicted another intense LMCT transition (HOMO − 4 → LUMO + 1) assignable to phenolate-O to the vacant metal-centered π* molecular orbital of Fe 3+ observed at 573 nm. 38,39,44 The observed bathochromic shift for complex 1 with respect to the previously reported iron(III) complex ([Fe(L 1 )phen]) could be due to the presence of auxochromes, such as amide and alkylthio groups. 44 Other ligand-centered electronic transitions (ππ* or nπ*) were observed at <300 nm (Figure S12).…”

“…Hepatotoxicity, skin-photosensitivity of the PDT agents, and the unavailability of an effective photosensitizer are the major concerns for effective photochemotherapeutic applications. − Transition-metal complexes and nanoconjugates, generating reactive oxygen species (ROS) on photoexcitation with higher-wavelength light, have emerged as viable and alternative solutions for photochemotherapeutic applications. − Iron­(III) generally forms less-labile and thermodynamically stable complexes with the π-donor ligands, e.g., carboxylate-O or phenolate-O. The complexation of iron­(III) with the π-donor ligands in an octahedral geometry typically results in a reduced energy gap between t 2g and e g * molecular orbitals − that lead to low-energy metal-centered or ligand-to-metal charge-transfer (LMCT) transition with the typical wavelength of absorption in the range of 450–600 nm. − When such complexes are activated with light at the LMCT band, there is typical homolytic fission of the metal–ligand bond, which consequently leads to the oxidation of the ligand (carboxylate-O or phenolate-O) and reduction of the iron­(III) center to iron­(II). − Such a light-induced intramolecular redox reaction is typically responsible for the generation of extremely cytotoxic ROS, such as superoxide anions (O 2 •– ) and hydroxyl radicals. − Therefore, the ability of the phenolate or carboxylate-based complexes of iron­(III) to yield ROS with low-energy or longer-wavelength light activation has shown potential as a promising strategic tool for photochemotherapeutic utility. Recently, our group, along with Chakravarty et al, has reported visible-light-induced hydroxyl radical-mediated photocytotoxicity with iron­(III)-phenolate/carboxylate-based complexes in different cancer cells. − However, the complexes did not satisfy the criteria for being ideal photochemotherapeutic agents as the majority of the iron­(III) complexes lacked target-specificity and showed photocytotoxicity only in the visible light (<600 nm).…”

La(iii)–curcumin-functionalized gold nanocomposite as a red light-activatable mitochondria-targeting PDT agent

“…[26][27][28][29][30] Over the last two decades, the coordination compounds of heavy metals (Ru, Pt, Ir, Rh, Os) in lieu of first-row transition metals have been given significant importance because of their kinetic inertness in biological media, ligand-tunable redox properties and luminescence properties in biological matrix, for their potential application in photochemotherapy, cellular imaging and theranostics. [31][32][33][34][35][36] Lanthanides with extended coordination number (>6) and higher order geometry, as well as high magnetic moments, have potentially emerged as new and alternative tools in drug design. For example, lanthanum carbonate is used for the treatment of hyperphosphatemia, 37 Gd(III) complexes are clinically used as MRI contrast agents, 38 and luminescent lanthanide-based compounds are used as optical probes.…”