Formaldehyde (FA), in the 0.2-0.4 mM range, is produced and maintained endogenously via enzymatic pathways. At these levels, FA can promote cell proliferation as well as mediate memory formation. Once elevated, FA stress is known to induce cognitive impairments, memory loss, and neurodegeneration owing to its potent DNA and protein cross-linking mechanisms. Optical imaging is a powerful noninvasive approach used to study FA in living systems; however, biocompatible chemical probes for FA are currently lacking. Herein, we report the design, synthesis, and biological evaluation of Formaldehyde Probe 1 (FP1), a new fluorescent indicator based on the 2-aza-Cope sigmatropic rearrangement. The remarkable sensitivity, selectivity, and photostability of FP1 has enabled us to visualize FA in live HEK293TN and Neuroscreen-1 cells. We envision that FP1 will find widespread applications in the study of FA associated with normal and pathological processes.

A method for the catalytic, enantioselective, intermolecular, 1,2-sulfenoamination of alkenes is described. Functionalization is achieved through the intermediacy of an enantioenriched, configurationally stable thiiranium ion generated by Lewis base activation of a readily available sulfur electrophile. A diverse set of anilines and benzylamines react with different styrenes to afford products in good yield and stereoselectivity. Downstream manipulation of the products is facilitated by deprotonation of the amines to enable carbon-sulfur bond cleavage.

Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The two-step, one-pot Davis-Beirut reaction was used to synthesize a library of 2H-indazoles and 1H-indazolones as putative inhibitors of MPO. A structure-activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H2O2 consumption assays. Docking studies as well as toxicophore and Lipinski analyses were performed. Fourteen compounds were found to be potent inhibitors with IC50 values <1 μM, suggesting these compounds could be considered as potential modulators of pro-oxidative tissue injury pertubated by the inflammatory MPO:H2O2:HOCl/HOBr system.

A general procedure for the asymmetric synthesis of highly substituted 1,2-amino alcohols in high yield and diastereoselectivity is described that uses organometallic additions of a wide range of nucleophiles to tertbutylsulfinimines as the key step. The addition of organolithium reagents to these imines follows a modified Davis model. The diastereoselectivity for this reaction depends significantly on both the nucleophile and electrophile. These highly substituted 1,2-amino alcohols are used to synthesize stereochemically diverse and structurally novel, polysubstituted 2,2′-methylene(bisoxazoline) ligands in high yields.

A number of (1H-1,2,3-triazol-1-yl)benzo[d]thiazoles were synthesized utilizing a versatile Cu-catalyzed azide-alkyne click reaction (CuAAC) on tautomeric benzo[4,5]thiazolo[3,2-d]tetrazole (1) and 2-azidobenzo[d]thiazole (2) starting materials. Moreover, one of the resulting products of this investigation, triazolbenzo[d]thiazole 22, was found to possess significant neuroprotective activity in human neuroblastoma (SH-SY5Y) cells.