RMM
Bioinorganic Chemistry
Smart MRI Probes
Our inorganic chemical biology projects are focusing MRI and optical imaging of intracellular nitric oxide (NO), L-cysteine, and pH environment of cancer cells. We have successfully designed and synthesized several Fe(II) complexes of macrocyclic ligands that are demonstrated as pH-responsive PARACEST MRI contrast agents (CAs). Very recently, our group has shown that the rhodamine appended high spin Fe(III)-O6 complexes as dual-modal T1 MRI/optical imaging agents for the imaging of NO and acidic pH environments of tumour cells. The MRI unit has functioned through second-sphere water interactions. The functionalization of this MRI core Fe(III)-O6 with C12-alkyl chain conjugates and interaction with external marker IR780 dye forms an aggregated matrix. It functioned as a smart “MRI-ON-Fluorescence ON” imaging agent for imaging acidic pH environments of tumour cells. Further, the biotin group is conjugated to the MRI core Fe(III)-O6 for delivering larger amounts of Fe(III) CA. The biotin attachment facilitated an increase in the ‘payload’ of CA in the tumor environment by targeting biotin metabolism and providing better visualization of cancer cells. In addition, several other Fe(III) and Mn(II/III) complexes are synthesized as redox-responsive T1-CAs. Specifically, a series of Mn(III) complexes of 1,4-diazepane-based bisphenolate ligands are reported as redox-active CA and are found to be sensitive towards the biological redox buffer molecule L-cysteine (Cys). We are working to develop more responsive MRI probes with and without optical imaging/ tumour targeting units.
Small Molecule Activation by Bioinspired Approach
O₂ Activation: Our dioxygen activation project involves synthesis, reactivity, and mechanism of Fe(II) complexes as bioinspired models for healthcare-related Fe(II)-dependent cysteine dioxygenases (CDO) and diketo dioxygenases (DKDO), which converts L-cysteine to L-cysteine sulfinic acid (sulfur oxidation) and C-C bond breaking respectively using O₂. The active sites of these enzymes are unique and poorly understood among the non-heme iron(II) dioxygenases family, in fact, the aforementioned typical 2-His-1-carboxylate facial triad is not adopted. The catalytic mechanisms and key intermediates are probed using Fe(II) and Ni(II) model complexes at the molecular level by combining spectroscopic and computational methods.
In nature, cytochrome P450, bleomycin, nonheme iron oxidases, copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), polysaccharide monooxygenases (PMO),7 methane monooxygenase (MMO) and tyrosinase (Ty) are known to activate C-H bonds at ambient condition using dioxygen. Inspired by the natural enzymes, our group was involved in designing and synthesizing bioinspired iron(II/III), nickel(II), and copper(II) complexes as catalysts for aromatic C-H bond activation since these may perform catalysis under mild conditions and turning the catalytic efficiency can be tuned by varying the ligand architecture and redox potential. We are working on probing the catalytic mechanism at the molecular level by combining synthetic, spectroscopic, and computational approaches.
CO₂ Activation: In addition, several bioinspired Cu(II) and Ni(II) complexes are reported as catalysts for the activation/ fixation of atmospheric CO₂ under mild conditions. The molecular structures of complexes and their CO₂-bound/CO3₂ – key intermediates are studied by spectral and redox methods and single-crystal X-ray analysis. The CO32- ion in these intermediates originates from atmospheric CO₂ , and the conversion occurs via geometrical and oxidation changes of metal centers. A series of Ni(II)/Cu(II) complexes of nitrogen-containing ligands are reported as the efficient and selective catalysts for the quantitative conversion of CO₂ into industrially important chemicals such as cyclic carbonates and carboxylic acids. The CO₂ fixation by our bioinspired complexes is found to be simultaneous and selective.
