Ligand dynamics and reactivity in trimetallic clusters

The general relationships between trinuclear cluster reactivity and the ligand dynamical processes in these systems are explored. Three specific mechanistic studies are presented: (1) the rate and stereochemistry of ligand addition to ₃-imidoyl complexes, (2) the factors influencing the rate of carbon-hydrogen bond activation in ₃-alkyne complexes, and (3) the origin of anomalously large kinetic deuterium isotope effect in metal to ligand and ligand to metal hydrogen transfer in trinuclear and binuclear complexes. In all three cases, the current state of the mechanistic studies are summarized and the possible rate of specific ligand dynamical processes in controlling the mechanism are put forth.     

Synthesis of the methanesulfonates of α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)emenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol,alpha styryl carbinol antifungal agents

The methanesulfonates of (α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol ( 1a, b ) are orally effective α-styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large-scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4-triazole simultaneously as a base transfer agent and nucleophile.     

Evaluation of heats of transition in scanning calorimetry

A procedure for the evaluation of heats of transition in scanning calorimetry has been developed. A formula for evaluation of the energy of fusion of a compound at its melting point is derived that takes into account the baseline shift that is attributable to the heat capacity change on melting. Several other calorimeter parameters of importance are discussed. These include heat exchange between calorimeter vessel and jacket, the time constant of the instrument, the scanning rate, and the heater placement.     

The dielectric constant and salt effects upon the acid hydrolysis of ethyl formate

The hydrolysis of ethyl formate catalysed by hydrochloric acid was studied at three temperatures in water-acetone media and in water media containing different concentrations of sodium nitrate. The effect of various ionic strengths and dielectric constants upon the rate of acid hydrolysis of ethyl formate is presented from the point of electrostatics and the results were compared to like effects upon the acid hydrolysis of ethyl acetate and methyl propionate. Neither the dielectric constant effect nor the salt effect lends itself readily to theoretical interpretation. It was assumed that a partial explanation of these anomalous results might be in the extrapolation of the acid radical to the simplest carboxylic acid. This suggestion was supported somewhat by the trends towards less adherance to the electrostatic theory at certain temperatures in the series methyl propionate, ethyl acetate and ethyl formate.     

Thin‐Film Infrared Spectroscopy of Acetonitrile

Acetonitrile and [D₃]acetonitrile in the vicinal region of a planar AgX fiber contain linear dipole–dipole linked oligomers as shown by 1) comparison of infrared band intensity ratios in the gaseous and condensed phases and 2) remarkable plots of absorbance (C? N stretch) versus time during evaporation from an AgX planar fiber element. The plots (CH₃CN 2252 cm^?1, CD₃CN 2262 cm^?1) reveal the presence of octamers, hexamers, tetramers, and dimers along with some heptamer, trimer, and monomer structures. A novel isotope effect arises from the somewhat smaller size of the CD₃CN resulting in an increase in the CN band intensity. The organized oligomers may be termed pseudocrystals and are the main components responsible for absorption intensity in the infrared spectrum of acetonitrile, on the AgX planar fiber or in an IR cell.     

Synthesis and binding affinities of novel SRIF-mimicking beta-D-glucosides satisfying the requirement for a pi-cloud at C1

[reaction: see text] The synthesis of four bioactive analogues of the somatostatin (SRIF-14) mimetic, beta-d-glucoside (+)-2, in which the C1 indole side chain is replaced with indole surrogates, has been achieved. These congeners, possessing the naphthyl, benzothiophene, benzyl, and benzofuran substituents, were predicted to satisfy the electrostatic requirements of the tryptophan binding pocket of SRIF. Unlike the previously described C4 picolyl and pyrazinyl congeners, these ligands bind the hSST4 receptor.     

3H-Indol-3-ols by a novel ring contraction

Treatment of α-hydroxy-α-phenyl-o-toluidide with phosphorus tribromide afforded a series of 4H-3,1-benzoxazines. These last, when reacted with potassium amide in liquid ammonia, ring contracted to 2,3-disubstituted 3H-indol-3-ols. The scope of this rearrangement was examined. The indolols on treatment with hot base were found to rearrange to indoxyls. Several of these as well as their N-alkylation products are described.     

Spin trapping chemistry of sodium 2-sulfonatophenyl t-butyl nitrone . a negatively charged water-soluble spin trap

A new water-soluble negatively charged spin trap, sodium 2-sulfonatophenyl $\text{t}$-butyl nitrone is described.     

RAMPED-UP NMR: multiplexed NMR-based screening for drug discovery

The crucial step in drug discovery is the identification of a lead compound from a vast chemical library by any number of screening techniques. NMR-based screening has the advantage of directly detecting binding of a compound to the target. The spectra resulting from these screens can also be very complex and difficult to analyze, making this an inefficient process. We present here a method, RAMPED-UP NMR, (Rapid Analysis and Multiplexing of Experimentally Discriminated Uniquely Labeled Proteins using NMR) which generates simple spectra which are easy to interpret and allows several proteins to be screened simultaneously. In this method, the proteins to be screened are uniquely labeled with one amino acid type. There are several benefits derived from this unique labeling strategy: the spectra are greatly simplified, resonances that are most likely to be affected by binding are the only ones observed, and peaks that yield little or no information upon binding are eliminated, allowing the analysis of multiple proteins easily and simultaneously. We demonstrate the ability of three different proteins to be analyzed simultaneously for binding to two different ligands. This method will have significant impact in the use of NMR spectroscopy for both the lead generation and lead optimization phases of drug discovery by its ability to increase screening throughput and the ability to examine selectivity. To the best of our knowledge, this is the first time in any format that multiple proteins can be screened in one tube.