Cationic yet Stronger Donor: A Surprising Partner Effect and the Partner Strategy in Accelerating a Pincer-Co Catalyzed Nitrile Hydroboration Reaction

A strategy to tune the catalytic behavior of a organometallic catalysts rather than ligand engineering is suggested in this work, by computationally studying the effect of (18-crown-6)K+, W(CO)3 and W(PMe3)3 on the reactivity of a Pincer-Co catalyzed nitrile hydroboration reaction through π-coordination to the ligand aromatic ring. These extra additives, as called by the partners, binds the central phenyl ring of the ligand by either dispersion or chemical bonding. The electron-richness of the cobalt center is tuned by the partner, and follows the order (18-crown-6)K+ > W(PMe3)3 > no partner > W(CO)3. While the influence of covalent W-containing partners parallels the electron-richness of W, the non-covalent partner, (18-crown-6)K+, surprisingly increases the donor ability of the Pincer ligand, through polarization effect. All the elementary steps involved in the nitrile hydroboration reaction are influenced by the partner, and the overall barrier is lowered by a surprisingly large extent of 4.9 kcal/mol in the presence of (18-crown-6)K+, suggesting a charming partner effect to be explored by experimentalists that the reactivity of a catalyst can be consecutively tuned without ligand modification.

Recent Advances in the Delivery Carriers and Chemical Conjugation Strategies for Nucleic Acid Drugs

With the development of new anticancer medicines, novel modalities are being explored for cancer treatment. For many years, conventional modalities, such as small chemical drugs and antibody drugs, have worked by “inhibiting the function” of target proteins. In recent years, however, nucleic acid drugs, such as ASOs and siRNAs, have attracted attention as a new modality for cancer treatment because nucleic acid drugs can directly promote the “loss of function” of target genes. Recently, nucleic acid drugs for use in cancer therapy have been extensively developed and some of them have currently been under investigation in clinical trials. To develop novel nucleic acid drugs for cancer treatment, it is imperative that cancer researchers, including ourselves, cover and understand those latest findings. In this review, we introduce and provide an overview of various DDSs and ligand modification technologies that are being employed to improve the success and development of nucleic acid drugs, then we also discuss the future of nucleic acid drug developments for cancer therapy. It is our belief this review will increase the awareness of nucleic acid drugs worldwide and build momentum for the future development of new cancer-targeted versions of these drugs.

[Co(TPP)]–Catalyzed Carbene Transfer from Acceptor–Acceptor Iodonium Ylides via N-enolate Carbene Radicals

Square-planar cobalt(II)-systems have emerged as powerful carbene transfer catalysts for the synthesis of numerous (hetero)cyclic compounds via cobalt(III)-carbene radical intermediates. Spectroscopic detection and characterization of reactive carbene radical intermediates is limited to a few scattered experiments, centering around mono-substituted carbenes. Here, we reveal the unique formation of disubstituted cobalt(III)-carbene radicals derived from a cobalt(II)-porphyrin complex and acceptor–acceptor λ3-iodaneylidenes (iodonium ylides) as carbene precursors and their catalytic application. Particularly noteworthy is the fact that iodonium ylides generate novel bis-carbenoid species via reversible ligand modification of the paramagnetic [Co(TPP)]-catalyst. Two interconnected catalytic cycles are involved in the overall mechanism, with a mono-carbene radical and an unprecedented N-enolate-carbene radical intermediate at the heart of each respective cycle. Notably, N-enolate formation is not a deactivation pathway, and both the N-enolate and carbene radical moieties can be transferred to styrene. The findings are supported by extensive experimental and computational studies.