8-Chloroguanosine: solid-state and solution conformations and their biological implications.
The three-dimensional structure of 8-chloroguanosine dihydrate was determined by X-ray crystallography. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), and the cell dimensions are a = 4.871 (1) A, b = 12.040 (1) A, and c = 24.506 (1) A. The structure was determined by direct methods, and least-squares refinement, which included all hydrogen atoms, converged at R = 0.031 for 1599 observed reflections. The conformation about the glycosidic bond is syn with chi CN = -131.1 degrees. The ribose ring has a C(2')-endo/C-(1')-exo (2T1) pucker, and the gauche+ conformation of the -CH2OH side chain is stabilized by an intramolecular O-(5')-H...N(3) hydrogen bond. Conformational analysis by means of 1H NMR spectroscopy showed that, in dimethyl sulfoxide, the sugar ring exhibits a marked preference for the C(2')-endo conformation (approximately 70%) and a conformation about the glycosidic bond predominantly syn (approximately 90%), hence similar to that in the solid state. However, the conformation of the exocyclic 5'-CH2OH group exhibits only a moderate preference for the gauche+ rotamer (approximately 40%), presumably due to the inability to form the intramolecular hydrogen bond to N(3) in a polar medium. The conformational features are examined in relation to the behavior of 8-substituted purine nucleosides in several enzymatic systems, with due account taken of the steric bulk and electronegativities of the 8-substituents.
D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006860:Hydrogen Bonding; D007778:Lactobacillus / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010430:Pentosyltransferases / Q000378:metabolism; D011687:Purines; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D011687:Purines; D006151:Guanosine; C043808:8-chloroguanosine; D010430:Pentosyltransferases; C021888:nucleoside deoxyribosyltransferase