Development of catalyst-free carbon-sulfur bond formation reactions under aqueous media and their applications

Methods for the carbon-sulfur bond formation under catalyst-free, aqueous conditions are extremely useful in organic synthesis and chemical biology. Our laboratory has developed methodologies to construct carbon-thiol bonds, carbon-sulfinic acid bonds, and carbon-disulfide bonds and such methodologies have been widely adopted by other research groups over multidisciplinary fields. In this article, our work on C–S bond formation in an aqueous solvent and its corresponding applications is summarized.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityPublished versionWe gratefully acknowledge the financial support from the Distinguished University Professor grant (Nanyang Technological University), AcRF Tier 1 grants from the Ministry of Education of Singapore (Nos. RG11/20 and RT14/20), and the Agency for Science, Technology and Research (A*STAR) for its MTC Individual Research Grant (No. M21K2c0114)

Recent developments in chemical conjugation strategies targeting native amino acids in proteins and their applications in antibody-drug conjugates

Many fields in chemical biology and synthetic biology require effective bioconjugation methods to achieve their desired functions and activities. Among such biomolecule conjugates, antibody-drug conjugates (ADCs) need a linker that provides a stable linkage between cytotoxic drugs and antibodies, whilst conjugating in a biologically benign, fast and selective fashion. This review focuses on how the development of novel organic synthesis can solve the problems of traditional linker technology. The review shall introduce and analyse the current developments in the modification of native amino acids on peptides or proteins and their applicability to ADC linker. Thereafter, the review shall discuss in detail each endogenous amino acid's intrinsic reactivity and selectivity aspects, and address the research effort to construct an ADC using each conjugation method.Ministry of Education (MOE)Nanyang Technological UniversityPublished versionWe gratefully acknowledge the financial support from Distinguished University Professor grant, Nanyang Technological University, Singapore, and AcRF Tier 1 grants from the Ministry of Education of Singapore (RG11/20 and RT14/20)

NH-bridged Dimeric Phosphazanes: Inorganic Molecular Switches based on Anion Responsive Bifurcated to Trifurcated Hydrogen Bond Transitions

Molecular machines and switches, supramolecular chemistry, and crystal engineering are vibrant areas of research. Organic chemists have devoted considerable efforts to develop a wide range of complex functional building blocks with enhanced properties and chemically responsive properties to advance these fields. However, the rational design of topologically versatile and chemically responsive building blocks in the main group arena is largely unexplored. Within this context, we have rationally designed a series of NH-bridged acyclic dimeric cyclodiphosphazanes species, [(μ-NH){PE(μ-NtBu)2PE(NHtBu)}2] (E= O and S), displaying bimodal bifurcated R21(8) and trifurcated R31(8,8) hydrogen bonding motifs. The reported species reversibly switch their topological arrangement in the presence of anions. Our results underscore these species as versatile building blocks for molecular machines and switches, as well as supramolecular chemistry and crystal engineering based on cyclophosphazane frameworks

N‐bridged acyclic trimeric poly‐cyclodiphosphazanes: highly tuneable cyclodiphosphazane building blocks

We have synthesized a completely new family of acyclic trimeric cyclodiphosphazane compounds comprising NH, N Pr, N Bu and NPh bridging groups. In addition, the first NH-bridged acyclic dimeric cyclophosphazane has been produced. The trimeric species display highly tuneable characteristics so that the distance between the terminal N(H)R moieties can be readily modulated by the steric bulk present in the bridging groups (ranging from ≈6 to ≈10 Å). Moreover, these species exhibit pronounced topological changes when a weak non-bonding NH⋅⋅⋅π aryl interaction is introduced. Finally, the NH-bridged chloride binding affinities have been calculated and benchmarked along with the existing experimental data available for monomeric cyclodiphosphazanes. Our results underscore these species as promising hydrogen bond donors for supramolecular host-guest applications