Synthesis and crystal structures of 3-hy-droxy-2,4-dimethyl-2-thio-phen-5-one and 3-hy-droxy-4-methyl-2-thio-phen-5-one.

The structures of two hy-droxy-thio-phenone derivatives related to the anti-biotic thiol-actomycin are presented. These are the racemic 3-hy-droxy-2,4-dimethyl-2-thio-phen-5-one, CHOS, and 3-hy-droxy-4-methyl-2-thio-phen-5-one, CHOS. The main structural feature of both compounds is (6) hydrogen-bonded chains formed between the OH and C=O groups.

Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation.

The fundamental pathophysiology of sickle cell disease is predicated by the polymerization of deoxygenated (T-state) sickle hemoglobin (Hb S) into fibers that distort red blood cells into the characteristic sickle shape. The crystal structure of deoxygenated Hb S (DeoxyHb S) and other studies suggest that the polymer is initiated by a primary interaction between the mutation βVal6 from one Hb S molecule, and a hydrophobic acceptor pocket formed by the residues βAla70, βPhe85 and βLeu88 of an adjacent located Hb S molecule. On the contrary, oxygenated or liganded Hb S does not polymerize or incorporate in the polymer.

Design, Synthesis, and Investigation of Novel Nitric Oxide (NO)-Releasing Prodrugs as Drug Candidates for the Treatment of Ischemic Disorders: Insights into NO-Releasing Prodrug Biotransformation and Hemoglobin-NO Biochemistry.

We have developed novel nitric oxide (NO)-releasing prodrugs of efaproxiral (RSR13) for their potential therapeutic applications in a variety of diseases with underlying ischemia. RSR13 is an allosteric effector of hemoglobin (Hb) that decreases the protein's affinity for oxygen, thereby increasing tissue oxygenation. NO, because of its vasodilatory property, in the form of ester prodrugs has been found to be useful in managing several cardiovascular diseases by increasing blood flow and oxygenation in ischemic tissues.