Our Research
With the main objective being designing “molecules with purpose,” our group aims to discover new catalytic or biomedical applications of organometallic complexes, particularly those centered around the N-heterocyclic carbenes and their variants. In this regard, our group emphasizes understanding the critical attributes of N-heterocyclic carbenes that underlie its unprecedented success in chemical catalysis. Our group has discovered several new late transition metal precatalysts of heteroatom stabilized singlet carbenes, including the N-heterocyclic carbenes, for utility in several C-C and C-N bond-forming reactions apart from cyclic lactide polymerizations. On the biomedical application front, our efforts explored the potentials of these heteroatom-stabilized singlet carbenes compounds in anticancer and antimicrobial studies.Chemical Catalysis
Our group uses heteroatom-stabilized singlet carbenes as ligand platforms to develop varied areas of homogeneous catalysis, including tandem reactions, bifunctional catalysis, asymmetric catalysis, cross-coupling, and polymerization reactions. To this end, numerous transition metal-based catalysts have been developed, from cheap and abundant first-row transition metals like iron, nickel, and copper to catalytically important second— and third-row metals like palladium, silver, gold, ruthenium, rhodium, and iridium.
Nickel and Palladium
By combining catalytic cycles in tandem, we aim to easily access intriguing motifs of industrial and biological relevance. Our group successfully demonstrated the utility of the one-pot Heck alkylation/intramolecular cyclization and Hiyama alkylation/intramolecular cyclization for producing biologically relevant benzofuran compounds. Recently, we used palladium mesoionic singlet carbene catalysis to activate small molecules like azide and isocyanides, generating heterocumulene-like carbodiimides and ketenimines.
Focusing on bifunctional catalysis, we continued towards catalytic construction of C-C bonds using bifunctional nickel precatalysts supported over N/O-functionalized N-heterocyclic carbenes that performed the desired base-free Michael addition at room temperature.
Targeting the oxidative addition step ubiquitous in numerous C-C cross-coupling reactions, our research demonstrated that more electron-rich palladium N-heterocyclic carbene complexes of the (NHC)2PdX2 (X = halide) types were more efficient than the comparatively less electron-rich PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed (NHC)PdX2(pyridine) ones for several C-C bond forming reactions namely, the Suzuki-Miyaura cross-couplings. The trans- and cis-[(NHC)2PdX2] (X=Cl, Br) complexes, synthesized from the corresponding silver analogs, also showed a similar trend in Sonogashira cross-coupling. Besides the PEPPSI complexes, we have also designed O-functionalized N-heterocyclic carbene complexes of Pd(II) and Au(I). Our group further designed several palladium precatalysts for the Hiyama coupling, employing the more challenging and much-desired organosilicon reagents. Palladium N-heterocyclic carbene chemistry was extended to abnormal N-heterocyclic carbenes as precatalysts for Cu-free and amine-free Sonogashira coupling in air.
Our group also reported the Suzuki-Miyaura cross-coupling of the more challenging aryl chloride substrates using homoscorpionate pyrazole-derived palladium complexes.
Coinage Metals
Extending beyond C-C bond formations, we pursued the C-N bond-forming reactions relevant to industry and academia, like the 100 % atom economic hydroamination of terminal alkynes and olefins. Interestingly enough, for the hydroamination of terminal alkynes, the gold(I) N-heterocyclic carbene complexes were found to be superior to the silver(I) analogs, while for the hydroamination of activated olefins, the more electron-deficient nickel complexes were found to be more active than their palladium counterparts.
Our group has shown the utility of Au(III) N-heterocyclic carbene complexes as catalysts for synthesizing beta-enaminones from 1,3-dicarbonyl compounds and aliphatic amines. In addition, we reported previously unseen long-range 1,7-bromination in the gold(III) complexes of a particular class of N-(aryl)imino functionalized N-heterocyclic carbene ligands.
Significantly enough, we reported only structurally characterized examples of the gold acetylide and thiol complexes of acyclic aminooxy carbene ligands and demonstrated their utility in A3 coupling for producing propargyl amines. In this connection, other metals like the neutral silver and gold complexes and cationic palladium and nickel complexes of pincer N-heterocyclic carbenes were also used in the A3 coupling. Super bulky N-heterocyclic carbene complexes of copper and silver complexes were explored in the A3 coupling of amine-aldehyde and alkynes.
Quite remarkably, our group employed inert coinage metal in the form of the gold(I) and silver(I) complexes of N-heterocyclic carbenes in producing biodegradable polymers by Ring-Opening Polymerization (ROP) of L-lactides, proceeding via a coordination-insertion pathway. Significantly enough, our group reported the first example of a gold-based initiator alongside nickel and copper complexes of phenoxy-ketimine ligands for the Ring-Opening Polymerization (ROP) of L-lactides.
Iron and Ruthenium
Furthermore, iron complexes of benzimidazole-derived N-heterocyclic carbenes also performed the Michael addition with activated olefins. Ruthenium catalysis was explored in the cyanosilylation of Aromatic Aldehydes, one-pot tandem dehydrogenative cross-coupling, and dual C=C and C=O bond reduction reactions.
Other Metals
Besides the N-heterocyclic carbenes, our group’s other interest lies in olefin polymerization and oxidation reactions. Of special mention is our work on titanium isopropoxide-based precatalysts for sulfoxidation reactions.
Biomedical Applications
Notably, our group was among the first to highlight the promising potential of palladium N-heterocyclic carbene complexes in anticancer studies. In particular, a palladium N-heterocyclic carbene complex was found to be 8 to 20 times more active than the frequently used metallodrug, cisplatin, against three commonly occurring human cancer cell lines, namely, cervical cancer (HeLa), breast cancer (MCF-7), and colon adenocarcinoma (HCT 116) under analogs in vitro conditions. The palladium complex inhibited cancer cell proliferation by arresting the cell cycle progression at the G2/M phase.
Our group demonstrated the utility of silver and gold N-heterocyclic carbene complexes in antimicrobial studies, with the gold(I) complexes being more effective. Cell morphological studies have suggested that the metal complexes affect the cytokinesis step of cell division. Our group also designed encapsulated nickel complexes, stabilized by strongly chelating N-heterocyclic carbene ligands and showing subdued cytotoxicity with the intent of their potential application as imminotolerent agents.
Metallophillic Interaction
Contrary to the prevailing notion, we reported stronger argentophilic interaction than aurophilic interaction in discrete N-heterocyclic carbene complexes, as evidenced by crystallography and low-temperature photoluminescence studies. These interactions were effectively utilized in synthesizing large 12-membered amido functionalized triazole and imidazole-based metallamacrocyclic compounds.
Biomimetic Chemistry
We designed structural and functional mimics of enzyme active sites like galactose oxidase, catechol dioxygenase, and catechol oxidase enzymes with a series of high-spin iron(III) and copper complexes of sterically demanding ligands. Heterodinuclear Zn(II)−Fe(III) and homodinuclear M(II)−M(II) (M - Zn, Ni, Co, Cu) complexes synthetically mimicked for hydrolases namely, Purple Acid Phosphatase (PAP) and other related enzymes.
