Hydrolysis of 2',3'-O-methyleneadenosin-5'-yl bis-5'-O-methyluridin-3'-yl phosphate: the 2'-hydroxy group stabilizes the phosphorane intermediate, not the departing 3'-oxyanion, by hydrogen bonding.
Hydrolytic reactions of 2',3'-O-methyleneadenosin-5'-yl bis-5'-O-methyluridin-3'-yl phosphate (1a) have been followed by RP HPLC over a wide pH range to elucidate the role of the 2'-OH group as an intermolecular hydrogen bond donor facilitating the cleavage of 1a. At pH < 2, where the decomposition of 1 is first-order in hydronium-ion concentration, the P-O5' and P-O3' bonds are cleaved equally rapidly. Over a relatively wide range from pH 2 to 4, the hydrolysis is pH-independent and the P-O5' bond is cleaved 1.6 times as rapidly as the P-O3' bond. At pH 6, the reaction becomes first-order in hydroxide-ion concentration and cleavage of the P-O3' bond starts to predominate, accounting for 89% of the overall hydrolysis in 10 mmol L(-)(1) aqueous sodium hydroxide. Under alkaline conditions, the 2'-OH group facilitates the cleavage of 1 by a factor of 27 compared to the 2'-OMe counterpart, the influence on the P-O3' and P-O5' bond cleavage being equal. Accordingly, the 2'-hydroxy group stabilizes the phosphorane intermediate, not the departing 3'-oxyanion, by hydrogen bonding.
Lönnberg
Tuomas
T
Department of Chemistry, University of Turku, FIN-20014 Turku, Finland. tuanlo@utu.fi
Korhonen
Jonna
J
D000241:Adenosine / Q000031:analogs & derivatives*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009711:Nucleotides / Q000737:chemistry; D010755:Organophosphates / Q000737:chemistry*; D013816:Thermodynamics; D014529:Uridine / Q000031:analogs & derivatives*
D009711:Nucleotides; D010755:Organophosphates; D000241:Adenosine; D014529:Uridine