Density functional and Monte Carlo studies of sulfur. I. Structure and bonding in S-n rings and chains (n=2-18) (vol 118, pg 9257, 2003)

Density functional calculations have been performed for ring isomers of sulfur with up to 18 atoms, and for chains with up to ten atoms. There are many isomers of both types, and the calculations predict the existence of new forms. Larger rings and chains are very flexible, with numerous local energy minima. Apart from a small, but consistent overestimate in the bond lengths, the results reproduce experimental structures where known. Calculations are also performed on the energy surfaces of S8 rings, on the interaction between a pair of such rings, and the reaction between one S8 ring and the triplet diradical S8 chain. The results for potential energies, vibrational frequencies, and reaction mechanisms in sulfur rings and chains provide essential ingredients for Monte Carlo simulations of the liquid–liquid phase transition. The results of these simulations will be presented in Part II.

Managment of adult lower respiratory tract infection in primary care

%0 per cent of antibiotic use in the community is for respiratory infection. this editorial considers wwh 8 out of 10 consultations for cough in general practice result inantibiotic prescribing

A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

The coronavirus main protease, Mpro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential Mpro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed Mpro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a Ki value of 35.3 M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.