Comparing Spontaneous Hydrolysis Rates of Activated Models of DNA and RNA
This research project aims to investigate difference in
relative rates concerning phosphoryl transfer relevant to biological
catalysis of DNA and RNA in the pH-independent reactions.
Activated Models of DNA and RNA for alkyl-aryl phosphate diesters
(with 4-nitrophenyl as a good leaving group) have successfully been
prepared to gather kinetic parameters. Eyring plots for the pH–
independent hydrolysis of 1 and 2 were established at different
temperatures in the range 100–160 °C. These measurements have
been used to provide a better estimate for the difference in relative
rates between the reactivity of DNA and RNA cleavage. Eyring plot
gave an extrapolated rate of kH2O = 1 × 10-10 s -1 for 1 (RNA model)
and 2 (DNA model) at 25°C. Comparing the reactivity of RNA
model and DNA model shows that the difference in relative rates in
the pH-independent reactions is surprisingly very similar at 25°. This
allows us to obtain chemical insights into how biological catalysts
such as enzymes may have evolved to perform their current
functions.
[1] Watson, J. D.; Crick, F. H. C., Molecular Structure of Nucleic Acids: A
Structure for Deoxyribose Nucleic Acid. Nature 1953, 171 (4356), 737-
738
[2] Lönnberg, T. A.; Helkearo, M.; Jancso, A.; Gajda, T., Mimics of small
ribozymes utilizing a supramolecular scaffold. Dalton Transactions
2012, 41 (11), 3328-3338.
[3] Wolfenden, R., Degrees of Difficulty of Water-Consuming Reactions in
the Absence of Enzymes. Chemical Reviews 2006, 106 (8), 3379-3396.
[4] Bunton, C. A., Mhala, M. M., Oldham, K. G. & Vernon, C. A. (1960) J.
Chem.Soc. 1960, 3293–3301.
[5] Kumamoto, J., Cox, J. R., Jr., & Westheimer, F. H. (1956) J. Am. Chem.
Soc.78, 4858–4860.
[6] Kirby, A. J. & Younas, M. (1970) J. Chem. Soc. B 1970, 510–513.
[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.
[8] Davis, A. M.; Hall, A. D.; Williams, A., Charge description of basecatalyzed
alcoholysis of aryl phosphodiesters: a ribonuclease model.
Journal of the American Chemical Society 1988, 110 (15), 5105-5108.
[9] Lönnberg, H., Cleavage of RNA phosphodiester bonds by small
molecular entities: a mechanistic insight. Organic & Biomolecular
Chemistry 2011, 9 (6), 1687-1703
[10] 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.
[11] Kosonen, M.; Yousefi-Salakdeh, E.; Strömberg, R.; Lönnberg, H., pHand
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)
[12] Åstro¨m, H. E. L. n.; E. Stro¨mberg, 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.
[13] Kosonen, M.; Yousefi-Salakdeh, E.; Strömberg, R.; Lönnberg, H., pHand
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).
[14] Jarvinen, P.; Oivanen, M.; Lonnberg, H., Interconversion and
phosphoester hydrolysis of 2',5'- and 3',5'-dinucleoside monophosphates:
kinetics and mechanisms. The Journal of Organic Chemistry 1991, 56
(18), 5396-5401.
[15] Kirby, A. J.; Younas, M., The reactivity of phosphate esters. Diester
hydrolysis. Journal of the Chemical Society B: Physical Organic 1970,
510-513.
[16] Kirby, A. J.; Younas, M., The reactivity of phosphate esters. Reactions
of diesters with nucleophiles. Journal of the Chemical Society B:
Physical Organic 1970, 1165-1172.
[17] Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth,
P.; Hengge, A. C. Journal of the American Chemical Society 2008, 130,
17858.
[1] Watson, J. D.; Crick, F. H. C., Molecular Structure of Nucleic Acids: A
Structure for Deoxyribose Nucleic Acid. Nature 1953, 171 (4356), 737-
738
[2] Lönnberg, T. A.; Helkearo, M.; Jancso, A.; Gajda, T., Mimics of small
ribozymes utilizing a supramolecular scaffold. Dalton Transactions
2012, 41 (11), 3328-3338.
[3] Wolfenden, R., Degrees of Difficulty of Water-Consuming Reactions in
the Absence of Enzymes. Chemical Reviews 2006, 106 (8), 3379-3396.
[4] Bunton, C. A., Mhala, M. M., Oldham, K. G. & Vernon, C. A. (1960) J.
Chem.Soc. 1960, 3293–3301.
[5] Kumamoto, J., Cox, J. R., Jr., & Westheimer, F. H. (1956) J. Am. Chem.
Soc.78, 4858–4860.
[6] Kirby, A. J. & Younas, M. (1970) J. Chem. Soc. B 1970, 510–513.
[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.
[8] Davis, A. M.; Hall, A. D.; Williams, A., Charge description of basecatalyzed
alcoholysis of aryl phosphodiesters: a ribonuclease model.
Journal of the American Chemical Society 1988, 110 (15), 5105-5108.
[9] Lönnberg, H., Cleavage of RNA phosphodiester bonds by small
molecular entities: a mechanistic insight. Organic & Biomolecular
Chemistry 2011, 9 (6), 1687-1703
[10] 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.
[11] Kosonen, M.; Yousefi-Salakdeh, E.; Strömberg, R.; Lönnberg, H., pHand
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)
[12] Åstro¨m, H. E. L. n.; E. Stro¨mberg, 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.
[13] Kosonen, M.; Yousefi-Salakdeh, E.; Strömberg, R.; Lönnberg, H., pHand
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).
[14] Jarvinen, P.; Oivanen, M.; Lonnberg, H., Interconversion and
phosphoester hydrolysis of 2',5'- and 3',5'-dinucleoside monophosphates:
kinetics and mechanisms. The Journal of Organic Chemistry 1991, 56
(18), 5396-5401.
[15] Kirby, A. J.; Younas, M., The reactivity of phosphate esters. Diester
hydrolysis. Journal of the Chemical Society B: Physical Organic 1970,
510-513.
[16] Kirby, A. J.; Younas, M., The reactivity of phosphate esters. Reactions
of diesters with nucleophiles. Journal of the Chemical Society B:
Physical Organic 1970, 1165-1172.
[17] Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth,
P.; Hengge, A. C. Journal of the American Chemical Society 2008, 130,
17858.
@article{"International Journal of Chemical, Materials and Biomolecular Sciences:61823", author = "Mohamed S. Sasi and Adel M. Mlitan and Abdulfattah M. Alkherraz", title = "Comparing Spontaneous Hydrolysis Rates of Activated Models of DNA and RNA", abstract = "This research project aims to investigate difference in
relative rates concerning phosphoryl transfer relevant to biological
catalysis of DNA and RNA in the pH-independent reactions.
Activated Models of DNA and RNA for alkyl-aryl phosphate diesters
(with 4-nitrophenyl as a good leaving group) have successfully been
prepared to gather kinetic parameters. Eyring plots for the pH–
independent hydrolysis of 1 and 2 were established at different
temperatures in the range 100–160 °C. These measurements have
been used to provide a better estimate for the difference in relative
rates between the reactivity of DNA and RNA cleavage. Eyring plot
gave an extrapolated rate of kH2O = 1 × 10-10 s -1 for 1 (RNA model)
and 2 (DNA model) at 25°C. Comparing the reactivity of RNA
model and DNA model shows that the difference in relative rates in
the pH-independent reactions is surprisingly very similar at 25°. This
allows us to obtain chemical insights into how biological catalysts
such as enzymes may have evolved to perform their current
functions.
", keywords = "DNA & RNA Models, Relative Rates, Reactivity.", volume = "8", number = "9", pages = "988-3", }
