Many ligands are structurally rigid and well-defined, e.g. N-heterocyclic carbenes display a fan-like structure with a defined buried volume. Here, we break this dogma by introducing more flexibility Show more
Many ligands are structurally rigid and well-defined, e.g. N-heterocyclic carbenes display a fan-like structure with a defined buried volume. Here, we break this dogma by introducing more flexibility around the catalytically active center by using acyclic (diamino)carbene (ADC) ligands. The ADC ligand was constructed in a straightforward protocol on the ruthenium center via methyl isocyanide coordination and subsequent reaction with amines such as pyrrolidine. Ligand flexibility in the formed (pyrrolidine)(methylamine)carbene ruthenium complex Ru-2 was demonstrated both in solution (variable temperature NMR) and in the solid state through crystallographic identification with the protic NH site oriented either distal or proximal to the ruthenium center. In contrast to their cyclic analogues, the Ru-ADC complexes are highly active in base-free transfer hydrogenation, with turnover numbers >1000. The base-free conditions allowed for the transformation of substrates with base-sensitive groups such as esters, amides, acids, and amines, substrates that typically fail to undergo transfer hydrogenation under classical conditions. The absence of base also enabled late-stage hydrogenation of more complex substrates, and it avoids complications such as corrosion attributed to KOH and related strong bases. Show less
Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cance Show more
Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cancer development, progression, and resistance to therapy. The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1)-antioxidant response element (ARE) signaling pathway is central to maintaining redox balance by regulating the expression of antioxidant and detoxification genes. Under physiological conditions, this pathway protects cells from oxidative damage, however, sustained activation of NRF2 in cancer, often due to mutations in KEAP1, supports tumor cell survival, drug resistance, and metabolic reprogramming. Recent studies demonstrate that NRF2 enhances glutathione (GSH) synthesis, induces detoxifying enzymes, and upregulates drug efflux transporters, collectively contributing to resistance against chemotherapy and targeted therapies. The inhibition of NRF2 using small molecules or dietary phytochemicals has shown promise in restoring drug sensitivity in preclinical cancer models. This review highlights the dual role of NRF2 in redox regulation and cancer therapy, emphasizing its potential as a therapeutic target. While targeting NRF2 offers a novel approach to overcoming treatment resistance, further research is needed to enhance specificity and facilitate clinical translation. Show less
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence Show more
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence of many pathologies, particularly chronic non-communicable diseases such as obesity and diabetes. Here, we examine decades of research identifying the complex immunometabolic signaling networks and the cellular and molecular events that occur in the setting of altered nutrient and energy exposures and offer a historical perspective. Furthermore, we describe recent advances such as the discovery that a broad complement of immune cells play a role in immunometabolism and the emerging evidence that nutrients and metabolites modulate inflammatory pathways. Lastly, we discuss how this work may eventually lead to tangible therapeutic advancements to promote health. Show less