We have investigated the influence of electron density on the three-center [N–I–N]+ halogen bond. A series of [bis(pyridine)iodine]+ and [1,2-bis((pyridine-2-ylethynyl)benzene)iodine]+ BF4– complexes substituted with electron withdrawing and donating functionalities in the para-position of their pyridine nitrogen were synthesized and studied by spectroscopic and computational methods. The systematic change of electron density of the pyridine nitrogens upon alteration of the para-substituent (NO2, CF3, H, F, Me, OMe, NMe2) was confirmed by 15N NMR and by computation of the natural atomic population and the π electron population of the nitrogen atoms. Formation of the [N–I–N]+ halogen bond resulted in >100 ppm 15N NMR coordination shifts. Substituent effects on the 15N NMR chemical shift are governed by the π population rather than the total electron population at the nitrogens. Isotopic perturbation of equilibrium NMR studies along with computation on the DFT level indicate that all studied systems possess static, symmetric [N–I–N]+ halogen bonds, independent of their electron density. This was further confirmed by single crystal X-ray diffraction data of 4-substituted [bis(pyridine)iodine]+ complexes. An increased electron density of the halogen bond acceptor stabilizes the [N···I···N]+ bond, whereas electron deficiency reduces the stability of the complexes, as demonstrated by UV-kinetics and computation. In contrast, the N–I bond length is virtually unaffected by changes of the electron density. The understanding of electronic effects on the [N–X–N]+ halogen bond is expected to provide a useful handle for the modulation of the reactivity of [bis(pyridine)halogen]+-type synthetic reagents.

The catalytic ability of a dinuclear Zn2+ complex of 1,3-bis-N1-(1,5,9-triazacyclododecyl)propane (3) in promoting the cleavage of an RNA model, 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1), and a DNA model, methyl p-nitrophenyl phosphate (MNPP, 4), was studied in methanol solution in the presence of added CH3O- at 25 degrees C. The di-Zn2+ complex (Zn2 :3), in the presence of 1 equiv of added methoxide, exhibits a second-order rate constant of (2.75 +/- 0.10) x 10(5) M(-1) s(-1) for the reaction with 1 at s(s)pH 9.5, this being 10(8)-fold larger than the k2 value for the CH3O- promoted reaction (kOCH3 = (2.56 +/- 0.16) x 10(-3) M(-1) s(-1)). The complex is also active toward the DNA model 4, exhibiting Michaelis-Menten kinetics with a KM and kmax of 0.37 +/- 0.07 mM and (4.1 +/- 0.3) x 10(-2) s(-1), respectively. Relative to the background reactions at s(s)pH 9.5, Zn2 :3 accelerates cleavage of each phosphate diester by a remarkable factor of 1012-fold. A kinetic scheme common to both substrates is discussed. The study shows that a simple model system comprising a dinuclear Zn2+ complex and a medium effect of the alcohol solvent achieves a catalytic reactivity that approaches enzymatic rates and is well beyond anything seen to date in water for the cleavage of these phosphate diesters.

An NMR study of the rates of hydroxide-promoted hydrolysis of formamide in aqueous media of varying mole fraction D(2)O (n) was performed at [LO(-)] = 1.42 M, T = 25 degrees C, to shed light on whether the mechanism involves a nucleophilic attack of HO(-) on the C=O or HO(-) acting as a general base to remove a proton from an attacking water. The solvent deuterium kinetic isotope effect under these conditions is inverse, k(OH)/k(OD) = 0.77 +/- 0.02 or k(OD)/k(OH) = 1.30 +/- 0.03. Proton inventory analysis of the k(n)() versus n data was undertaken through NLLSQ fits to equations representing four possible mechanisms encompassing nucleophilic and general base ones with waters of solvation on the attacking hydroxide, and with or without waters of solvation on the developing amide hydrate oxyanion. Both nucleophilic and general base mechanisms can be accommodated, but there are restraints on each that are discussed. The preferred mechanism is a nucleophilic one proceeding through a transition state having two solvating waters remaining on the attacking hydroxide and three additional waters attached to the developing amide hydrate oxyanion.

The potentiometric titrations of nine lanthanideIII triflates, ZnII and CuII triflate, and the NiII, CoII, MgII, and TiIV perchlorates were obtained in methanol to determine the titration constants (defined as the sspH at which the [OCH3–]/[Mx+]t ratios are 0.5 and 1.5) as well as the apparent sspKa values for deprotonation of the metal-bound solvent molecules. The titrations were performed under various conditions with and without added salts as electrolytes, and the variations in the titration constants are discussed. In selected cases (La3+, Zn2+) the titration profiles were analyzed using a complex fitting program to obtain information about the species present in solution.Key words: potentiometric titration, methanol, sspH, metal ion, lanthanides, apparent sspKa.

The methanolyses of a series of O,O-diethyl O-aryl phosphates (2,5) and O,O-diethyl S-aryl phosphorothioates (6) promoted by methoxide and two metal ion systems, (La3+)2(-OCH3)2 and 4:Zn2+:-OCH3 (4 = 1,5,9-triazacyclododecane) has been studied in methanol at 25 degrees C. Brønsted plots of the logk2 values vs. pKa for the phenol leaving groups give beta(lg) values of -0.70, -1.43 and -1.12 for the methanolysis of the phosphates and -0.63, -0.87 and -0.74 for the methanolysis of the phosphorothioates promoted by the methoxide, La3+ and Zn2+ systems respectively. The kinetic data for the metal-catalyzed reactions are analyzed in terms of a common mechanism where there is extensive cleavage of the P-XAr bond in the rate-limiting transition state. The relevance of these findings to the mechanism of action of the phosphotriesterase enzyme is discussed.