The Hydrolysis of Alkyl-3'Uridyl Phosphate or Acetate Esters Can be Used to Estimate the pKa of Neopentyl Alcohol
الكلمات المفتاحية:
Phosphate and Acetate Hydrolysis، Neopentanolالملخص
The research project aim is to determine the pKa of neopentanol alcohol because it has been used in many biological models as a leaving group. The pKa of neopentanol alcohol can be obtained by measuring the observed rate for compound 1 under identical conditions to that reported for a similar series of alkyl uridyl phosphate diesters. The pKa of neopentyl alcohol was derived from the reported Brønsted plot for the hydroxide-catalyzed hydrolysis of alkyl uridyl phosphate diesters and the observed rate constant for uridine 3´-neopentyl phosphate 1. As a result, the best estimate for the pKa of neopentanol alcohol can established from this work. The corresponding pKa of neopentyl alcohol from the observed rate of the hydroxide-catalyzed hydrolysis of 1 is 17.3, which is significantly greater than the value of 15.5 used in earlier reports. This new value can be used now to estimate a better half- life for pH-independent DNA cleavage. This allows us to use correctly the neopentyl group as a mimicked model for biological systems such as that in DNA cleavage
المراجع
Clayden, G., Warren and Wothers, Organic chemistry. First ed.; Oxford University Press: Oxford New York, pp. 181–191, 2001.
Bruice, T. C.; Fife, T. H.; Bruno, J. J.; Brandon, N. E., Hydroxyl Group Catalysis. II. The Reactivity of the Hydroxyl Group of Serine. The Nucleophilicity of Alcohols and the Ease of Hydrolysis of Their Acetyl Esters as Related to Their pKa'*. Biochemistry 1962, 1 (1), 7-12.
Bunton, C. A., Mhala, M. M., Oldham, K. G. & Vernon, C. A. (1960) J. Chem.Soc. 1960,
–3301.
Kosonen, M.; Yousefi-Salakdeh, E.; Strömb erg, R.; Lönnberg, H., pH- and buffer- independent cleavage and mutual isomerization of uridine 2[prime or minute]- and 3[prime or minute]-alkyl phosphodiesters: implications for the buffer catalyzed cleavage of RNA. Journal of the Chemical Society, Perkin Transactions 2 1998, (7).
Williams, N. H.; Takasaki, B.; Wall, M.; Chin, J., Structure and Nuclease Activity of Simple Dinuclear Metal Complexes: Quantitative Dissection of the Role of Metal Ions. Accounts of Chemical Research 1999, 32 (6), 485-493.
Lönnberg, T. A.; Helkearo, M.; Jancso, A.; Gajda, T., Mimics of small ribozymes utilizing a supramolecular scaffold. Dalton Transactions 2012, 41 (11), 3328-3338.
Åström, H. E. L. n.; E. Strömberg, R., Acidity of secondary hydroxyls in ATP and adenosine analogues and the question of a 2',3'-hydrogen bond in ribonucleosides. Journal of the American Chemical Society 2004, 126 (45), 14710-14711.
Ora, M.; Hanski, A., Stepwise Mechanism of Hydroxide Ion Catalyzed Cyclization of Uridine 3′-Thiophosphates. Helvetica Chimica Acta 2011, 94 (9), 1563-1574.
Wolfenden, R., Degrees of Difficulty of Water-Consuming Reactions in the Absence of Enzymes. Chemical Reviews 2006, 106 (8), 3379-3396.
Kirby, A. J.; Marriott, R. E., General base catalysis vs. medium effects in the hydrolysis of an RNA model. Journal of the Chemical Society, Perkin Transactions 2 2002, (3), 422-427.
Schroeder, G. K.; Lad, C.; Wyman, P.; Williams, N. H.; Wolfenden, R., The time required for water attack at the phosphorus atom of simple phosphodiesters and of DNA. Proceedings of the National Academy of Sciences of the United States of America 2006, 103 (11), 4052- 4055.
Harned, H.; Owen, B. Reinhold Publications., New York, USA 1958.
Florian, J.; Aqvist, J.; Warshel, A., On the Reactivity of Phosphate Monoester Dianions in Aqueous Solution: Bronsted Linear Free-Energy Relationships Do Not Have an Unique Mechanistic Interpretation. Journal of the American Chemical Society 1998, 120 (44), 11524- 11525.
Kamerlin, S. C. L.; Florián, J.; Warshel, A., Associative Versus Dissociative Mechanisms of Phosphate Monoester Hydrolysis: On the Interpretation of Activation Entropies. ChemPhysChem 2008, 9 (12), 1767-1773.
Bunton, C. A.; Mhala, M. M.; Oldham, K. G.; Vernon, C. A., 660. The reactions of organic phosphates. Part III. The hydrolysis of dimethyl phosphate. Journal of the Chemical Society (Resumed) 1960, 3293-3301.
