THE COORDINATION OF VO2+ TO HYDROXAMATE BINDERS AS STUDIED BY ORIENTATION SELECTIVE ESEEM SPECTROSCOPY

摘要

The binding of VO2+ to chiral dihydroxamate binders facilitates the transport of VO2+ through the cell membrane into the cell interior, where it was shown to simulate glucose metabolism (Shechter, Y;; Shisheva, A.; Lazar, R.; Libman, J.; Shanzer, A. Biochemistry 1992, 31, 2063). The unique structure of the binders relies on a modular dipodal topology which generates different binding cavities. The coordination of VO2+ to two homologues of these ligands, RL261 and RL239, having different dipod arms but identical donor groups, was investigated by orientation selective electron spin echo envelope modulation (ESEEM) spectroscopy. Relatively deep modulations were observed for the N-14 nuclei in the hydroxamate groups in both complexes owing to the fulfillment of the cancellation condition at similar to 9 GHz. The Fourier transform Fl ESEEM spectra showed four peaks, three corresponding to the nuclear quadrupole resonance (NQR) lines, v(o), v(-), and v(+), and one to the overtone, 2(vm). In VO-RL261 the NQR and the 2(vm) peaks appear at 1.75, 2.15, 3.9, and 6.0 MHz, respectively, whereas in VO-RL239 they are at 1.75, 2.05, 3.9, and 6.2 MHz, respectively. From the positions of these peaks the N-14 quadrupole coupling constant, e(2)qQ/h, the asymmetry parameter, eta, and the isotropic hyperfine constant a(iso), were estimated to be 4.0, 0.87, and 2.5 MHz, respectively, for VO-RL261 and 3.8, 0.91, and 2.8 MHz, respectively, for VO-RL239. The unique orientation dependence of the v(+) peak, which practically disappeared when the field was set to A(parallel to)(V-51), indicates that the principal axis of the quadrupole tenser, z'', is either parallel or perpendicular to the VO axis. In order to obtain more accurate values of the above parameters and to determine the anisotropic hyperfine component, a(perpendicular to), as well as the orientations of the hyperfine and quadrupole tensors with respect to the VO axis, a series of simulations were carried out. The best fit parameters showed that a(perpendicular to) is rather large (0.6-0.7 MHz) and cannot be neglected and that a(iso) is smaller than expected, i.e., 1.6-1.8 MHz. We also obtained that z'' is to a good approximation parallel to the VO axis indicating that the two hydroxamate planes are perpendicular to the VO axis in both complexes. Two possible structures, one with a C-2 symmetry, trans configuration, and one with a sigma(xz) symmetry, cis configuration, were considered in the simulations and the latter was found to agree better with the experimental results. The slight differences in the parameters obtained for VO-RL261 and VO-RL239 are attributed to electronic effects induced by the different groups bounded to the hydroxamate carbonyl. [References: 45]