Oxaliplatin, a platinum compound in broad clinical use, can induce cell death through a nucleolar stress pathway rather than the canonical DNA damage response studied for other Pt(II) compounds. Previous work has found that the oxaliplatin 1,2‐diaminocyclohexane (DACH) ring but not the oxalate leaving group is important to the ability to induce nucleolar stress. Here we study the influence of DACH ring substituents at the 4‐position on the ability of DACH−Pt(II) compounds to cause nucleolar stress. We determine that DACH−Pt(II) compounds with 4‐position methyl, ethyl, or propyl substituents induce nucleolar stress, but DACH−Pt(II) compounds with 4‐isopropyl substituents do not induce nucleolar stress. This effect is independent of whether the substituent is in the axial or equatorial position relative to the trans diamines of the ligand. These results suggest that spatially sensitive interactions could be involved in the ability of platinum compounds to cause nucleolar stress.

Alkenes are used ubiquitously as starting materials and synthetic targets in all areas of chemistry. Controlling their geometry and position along a chain is vital to their reactivity and properties yet remains challenging. Alkene isomerization is an atom-economical process to synthesize targeted alkenes, and selectivity can be controlled using transition metal catalysts. The development of mild, selective isomerization reactivity has enabled efficient tandem catalytic systems for the remote functionalization of alkenes, a process in which a starting alkene is isomerized to a new position prior to the functionalization step. The key challenges in developing isomerization catalysts for remote functionalization applications are (i) a lack of modularity in the catalyst structure and (ii) the requirement of nonmodular and/or harsh additives during catalyst activation. We address both challenges with a modular (NHC)Ni(0)/silane catalytic system (NHC, N-heterocyclic carbene), demonstrating the use of triaryl silanes and readily accessible (NHC)Ni(0) complexes to form the proposed active (NHC)(silyl)Ni−H species in situ. We show that modification of the steric and electronic nature of the catalyst via modification of the ancillary ligand and silane partner, respectively, is easily achieved, creating a uniquely versatile catalytic system that is effective for the formation of internal alkenes with high yield and selectivity for the E-alkene. The use of silanes as mild activators enables isomerization of substrates with a variety of functional groups, including acid-labile groups. The broad substrate scope, enabled by catalyst design, makes this catalytic system a strong candidate for use in tandem catalytic applications. Preliminary mechanistic studies support a Ni−H insertion/elimination pathway.

Hydrogen sulfide (H 2 S) is an important biomolecule, and selfimmolative thiocarbamates have shown great promise as triggerable H 2 S donors with suitable analogous control compounds; however, thiocarbamates with electron-deficient payloads are less efficient H 2 S donors. We report here the synthesis and study of a series of N-methylated esterase-triggered thiocarbamates that block the postulated unproductive deprotonation-based pathway for these compounds. The relative reaction profiles for H 2 S release across a series of electron-rich and electron-poor N-Me aniline payloads are examined experimentally and computationally. We show that thiocarbamate N-methylation does block some side reactivity and increases the H 2 S release profiles for electron-poor donors. Additionally, we show that isothiocyanate release is not a competitive pathway, and rather that the reduced efficiency of electronpoor donors is likely due to other side reactions.

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Recent efforts have expanded the development of small molecule donors that release the important biological signaling molecule hydrogen sulfide (H 2 S). Previous work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release H 2 S directly, albeit inefficiently. However, TDZNs showed promising efficacy in H 2 S-mediated relaxation in ex vivo aortic ring relaxation models. Here, we show that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to H 2 S by the enzyme carbonic anhydrase (CA) rather than releasing H 2 S directly as previously reported.