title: A simple DNase model system comprising a dinuclear Zn(II) complex in methanol accelerates the cleavage of a series of methyl aryl phosphate diesters by 10(11)-10(13).
abstract: The di-Zn(II) complex of 1,3-bis[ N1, N1'-(1,5,9-triazacyclododecyl)]propane with an associated methoxide ( 3:Zn(II) 2: (-)OCH 3) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters ( 6) was studied at s (s)pH 9.8 in methanol at 25.0 +/- 0.1 degrees C. Plots of k obs vs [ 3:Zn(II) 2: (-)OCH 3] free for all members of 6 show saturation behavior from which K(M) and kcat (max) were determined. The second order rate constants for the catalyzed reactions (kcat (max)/K(M)) for each substrate are larger than the corresponding methoxide catalyzed reaction (k 2 (-OMe)) by 1.4 x 10(8) to 3 x 10 (9)-fold. The values of k cat (max) for all members of 6 are between 4 x 10(11) and 3 x 10(13) times larger than the solution reaction at s (s)pH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO 2 or C(O)OCH 3 groups. Based on the linear Brønsted plots of k cat (max) vs s (s)pKa of the phenol, beta lg values of -0.57 and -0.34 are determined respectively for the catalyzed methanolysis of "regular" substrates that do not contain the ortho-NO 2 or C(O)OCH 3 groups, and those substrates that do. The data are consistent with a two step mechanism for the catalyzed reaction with rate limiting formation of a catalyst-coordinated phosphorane intermediate, followed by fast loss of the aryloxy leaving group. A detailed energetics calculation indicates that the catalyst binds the transition state comprising [CH 3O (-): 6], giving a hypothetical [ 3:Zn(II) 2:CH 3O (-): 6] complex, by -21.4 to -24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO 2 or C(O)OCH 3 groups.
authors.affiliation: Department of Chemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Neverov
authors.forename: C Tony
authors.initials: CT
authors.lastname: Liu
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Bunn
authors.forename: David
authors.initials: D
authors.lastname: Edwards
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: White
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Melnychuk
authors.forename: R Stan
authors.initials: RS
authors.lastname: Brown
mesh_terms: D001372:Aza Compounds / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D003851:Deoxyribonucleases / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D000432:Methanol / Q000031:analogs & derivatives*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000737:chemistry*; D010755:Organophosphates / Q000737:chemistry; D011407:Propane / Q000031:analogs & derivatives*; D013056:Spectrophotometry, Ultraviolet; D015032:Zinc / Q000737:chemistry*
chemical_list: D001372:Aza Compounds; D009942:Organometallic Compounds; D010755:Organophosphates; D003851:Deoxyribonucleases; D015032:Zinc; D011407:Propane; D000432:Methanol