Tailoring B-doped silicon nanocrystal surface chemistry phosphorus pentachloride - mediated surface alkoxylation.

Doped silicon nanocrystals (SiNCs) are promising materials that could find use in a wide variety of applications. Realizing methods to tailor the surface chemistry of these particles offers greater tunability of the material properties as well as broader solvent compatibility. Herein, we report organic-soluble B-doped SiNCs prepared a thermal processing method followed by phosphorus pentachloride etching induced functionalization with alkoxy ligands of varied chain lengths.

A Potent Fluorescent Reversible-Covalent Inhibitor of Cardiac Muscle Contraction.

Compounds that directly modulate the response of the cardiac sarcomere have potential in the treatment of cardiac disease. While a number of sarcomere activators have been discovered and extensively studied, very few inhibitors have been identified. We report a potent cardiac sarcomere inhibitor, DN-F01, targeting the cardiac muscle thin filament protein troponin complex.

The Role of Electrostatics in the Mechanism of Cardiac Thin Filament Based Sensitizers.

Heart muscle contraction is regulated by calcium binding to cardiac troponin C. This induces troponin I (cTnI) switch region binding to the regulatory domain of troponin C (cNTnC), pulling the cTnI inhibitory region off actin and triggering muscle contraction. Small molecules targeting this cNTnC-cTnI interface have potential in the treatment of heart disease.

Thioimidate Bond Formation between Cardiac Troponin C and Nitrile-containing Compounds.

We have investigated the mechanism and reactivity of covalent bond formation between cysteine-84 of the regulatory domain of cardiac troponin C and compounds containing a nitrile moiety similar to the calcium sensitizer levosimendan. The results of modifications to the levosimendan framework ranged from a large increase in covalent bond formation to complete inactivity. We present the biological activity of one of the most potent compounds.

Optimizing fluorine labelling for F solid-state NMR in oriented biological systems.

When planning a fluorine labeling strategy for F solid state NMR (ssNMR) studies of the structure and/or mobility of fluorine labeled compounds in situ in an oriented biological system, it is important to characterize the NMR properties of the label. This manuscript focuses on the characterization of a selection of aromatic fluorine compounds in dimyristoylphosphatidylcholine bilayers using F ssNMR from the standpoint of determining the optimum arrangement of fluorine nuclei on a pendant aromatic ring before incorporation into more complex biological systems.

Feasibility of trifluoromethyl TROSY NMR at high magnetic fields.

Insights into the structure and dynamics of large biological systems has been greatly improved by two concurrent NMR approaches: the application of transverse relaxation-optimized spectroscopy (TROSY) techniques in multi-dimensional NMR, especially the methyl-TROSY, and the resurgence of F NMR using trifluoromethyl (CF) probes. Herein we investigate the feasibility of combining these approaches into a trifluoromethyl-TROSY experiment. Using a CF-labelled parvalbumin, we have evaluated the natural abundance C-F correlation spectra and find no indication of a CF TROSY at high magnetic fields.

Reversible Covalent Reaction of Levosimendan with Cardiac Troponin C in Vitro and in Situ.

The development of calcium sensitizers for the treatment of systolic heart failure presents difficulties, including judging the optimal efficacy and the specificity to target cardiac muscle. The thin filament is an attractive target because cardiac troponin C (cTnC) is the site of calcium binding and the trigger for subsequent contraction. One widely studied calcium sensitizer is levosimendan.