95055-00-8Relevant academic research and scientific papers
13C NUCLEAR MAGNETIC RESONANCE CHEMICAL SHIFTS IN STYRENES; SUBSTITUENT AND SOLVENT EFFECTS
Happer, Duncan A. R.
, p. 1673 - 1680 (1984)
The 13C n.m.r. chemical shifts of a series of meta- and para-X-substituted styrenes (X = H, NMe2, OMe, Me, F, Cl, Br, I, CF3, CO2Me, Ac, CN, NO2, NMe3+) have been determined in seven different solvents (75percent EtOH-D2O, EtOH, Me2SO, Me2CO, CDCl3, CCl4, and C6H6).The data for the side-chain carbons and for the ring carbon para- to the substituent (C6) in the meta-series have been analysed and used as a basis for assessing the effect of solvent on ?I, ?RO, ?RBA, and ?R-.
Novel irreversible butyrylcholinesterase inhibitors: 2-chloro-1-(substituted-phenyl)ethylphosphonic acids.
Zhang, Nanjing,Casida, John E
, p. 1281 - 1290 (2007/10/03)
2-Chloroethylphosphonic acid (ethephon) as the dianion phosphorylates butyrylcholinesterase (BChE) at its active site. In contrast, the classical organophosphorus esterase inhibitors include substituted-phenyl dialkylphosphates (e.g., paraoxon) with electron-withdrawing aryl substituents. The chloroethyl and substituted-phenyl moieties are combined in this study as 2-chloro-1-(substituted-phenyl)ethylphosphonic acids (1) to define the structure--activity relationships and mechanism of BChE inhibition by ethephon and its analogues. Phenyl substituents considered are 3- and 4-nitro, 3- and 4-dimethylamino, and 3- and 4-trimethylammonium. Phosphonic acids were synthesized via the corresponding O,O-diethyl phosphonate precursors followed by deprotection with trimethylsilyl bromide. They decompose under basic conditions about 100-fold faster than ethephon to yield the corresponding styrene derivatives. Electron-withdrawing substituents on the phenyl ring decrease the hydrolysis rate while electron-donating substituents increase the rate. The 4-trimethylammonium analogue has the highest affinity (K(i)=180 microM) and potency (IC(50)=19 microM) in first binding reversibly at the substrate site (possibly with stabilization in a dianion--monoanion environment) and then progressively and irreversibly inhibiting the enzyme activity. These observations suggest dissociation of chloride as the first and rate-limiting step both in the hydrolysis and by analogy in phosphorylation of BChE by bound at the active site.
