Catalysis of phosphodiester transesterification by dinuclear Cu(II) complexes: The role of the second Cu(II) ion

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 13, 1997, Pages 1779-1784

  Liu, Shanghao ^a   Hamilton, Andrew D ^a  

^a UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER ION; ESTER; RIBOZYME;

ARTICLE; CATALYSIS; ENZYME MECHANISM; ESTERIFICATION; RNA METABOLISM;

EID: 0030753264     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00303-X     Document Type: Article

References (28)

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4. Liu, S.; Hamilton, A. D. Tetrahedron Lett. 1997, 38, 1107.
5. 5a For comparison of the behaviors of RNA and p-nitrophenyl phosphodiesters similar to HPNPP as substrates for ribonuclease A and its mutants, see (a) Thompson, J. E.; Raines, R. T. J. Am. Chem. Soc. 1994, 116, 5467.
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7. For a recent review on multi-metal ion phosphodiesterases see: Strater, N.; Lipscomb, W. N.; Klabunde, T.; Krebs, B. Angew. Chem. Int. Ed. Engl. 1996, 35, 2024.
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19. 6O calcd 444.1698, obsd 444.1693.
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23. 2]) for the chlorides corresponding to 4 and 5, respectively.
24. Linkletter, B.; Chin, J. Angew. Chem. Int. Ed. Engl. 1995, 34, 472.
25. o is the initial HPNPP concentration.
26. Hurst, P.; Takasaki B. K.; Chin. J. J. Am. Chem. Soc. 1996, 118, 9982.
27. 6
28. These two pH-rate profiles are unusual in that the rate increases only slightly from pH 7.0 to 8.0 and decreases sharply from pH 8.0 to 8.5. Complex 1 is known to dimerize when one of the Cu(II) ion-bound water molecules become deprotonated (the first pKa of 1 is 6.6) and the dimer is catalytically inactive.14 The unusual flatness of the pH-rate profiles from pH 7.0 to 8.0 is probably due to increased dimerization of the catalysts which slows the rate increase by decreasing the concentration of the active Cu(II)-OH forms. On the other hand, the unusually large rate decrease from pH 8.0 to 8.5 is probably due to inhibition of the activity of the catalysts by AMPSO in the buffer solution. The Cu(II) ion in 1 is more accessible than that in 2 to other potential ligands. Also, the secondary amino group in AMPSO is not as steric hindered as the tertiary amino group in HEPES. Therefore, it is possible that the amino group in AMPSO binds to the Cu(II) ion in 1 and in the bipyridine subunit of 5. As a result, the Cu(II) ion becomes inaccessible to the substrate and the activities of 1 and 5 are diminished. The above explanation is supported by our unpublished observation that 1 and 5 also show much lower activities in the TAPSO (also a secondary amine) buffers than in the HEPES buffer at the same pH (7.5-8.0).