Biomedical subjects

P Manikandan

Publications and source records attributed to P Manikandan.

10 recordsLinked to original sources

PubMed2001

Lattice-dictated conformers in bis(pyrazolyl)pyridine-based iron(II) complexes: Mössbauer, NMR, and magnetic studies.

Iron(II) complexes [FeL(2)](ClO(4))(2).CH(3)CN, [FeL(2)](BPh(4))(2).2CH(3)CN, and [FeL(2)](PF(6))(2) with an FeN(6) chromophore of the same ligand L (2,6-bis(3,5-dimethylpyrazol-1-ylmethyl)pyridine) and differing counterions have been made and their crystal and molecular structures determined. The first two crystallized in triclinic space group P(-)1, and the third, with PF(6)(-) anion in Ibca space group. The FeL(2) complex ions in all lattices have similarly distorted octahedral geometry. Variable-temperature Mössbauer spectra of [FeL(2)](ClO(4))(2).CH(3)CN and [FeL(2)](PF(6))(2) measured in the temperature range 1.7-300 K reveal temperature-dependent populations of two different spin states with increased amount of low-spin form at high temperatures, a phenomenon unlike the normal spin crossover behavior; this abnormal behavior is interpreted here as due to the presence of two different conformations. It is very interesting to note that the two different compounds have similar spectra, Mössbauer parameters, and temperature dependence. But the variable-temperature Mössbauer spectra of [FeL(2)](BPh(4))(2).2CH(3)CN in the range 20-300 K do not show the presence of such different species but exhibit a clear phase transition at approximately 200 K. This phase transition is further supported by SQUID measurements. The results of variable-temperature (1)H NMR in CD(3)CN and the solution susceptibility measurement of all complexes also support the presence of high-spin and low-spin forms in solution. Hence, the complex ion [FeL(2)](2+) exhibits a thermally driven interconversion between low-spin and a high-spin structural forms-a phenomenon observed in the solid and solution states due to ligand dynamics. This is not due to the well-known spin crossover phenomenon. These results are compared with the case of normal spin crossover seen in [FeL'(2)](ClO(4))(2) (L' = 2,6-(bis(pyrazol-1-ylmethyl)pyridine)).

Journal Article↗

PubMed2001

Proton positions in the Mn(2+) binding site of concanavalin A as determined by single-crystal high-field ENDOR spectroscopy.

High-field (95 GHz) pulsed EPR and electron-nuclear double resonance (ENDOR) techniques have been used for the first time to determine coordinates of ligand protons of a high-spin metal center in a protein single crystal. The protein concanavalin A contains a Mn(2+) ion which is coordinated to two water molecules, a histidine residue, and three carboxylates. Single crystals of concanavalin A were grown in H(2)O and in D(2)O to distinguish the exchangeable water protons from the nonexchangeable protons of the imidazole group. Distinct EPR transitions were selected by performing the ENDOR measurements at different magnetic fields within the EPR spectrum. This selection, combined with the large thermal polarization achieved at 4.5 K and a magnetic field of approximately 3.4 T allowed us to assign the ENDOR signals to their respective M(S) manifolds, thus providing the signs of the hyperfine couplings. Rotation patterns were acquired in the ac and ab crystallographic planes. Two distinct crystallographic sites were identified in each plane, and the hyperfine tensors of two of the imidazole protons and the four water protons were determined by simulations of the rotation patterns. All protons have axially symmetric hyperfine tensors and, by applying the point-dipole approximation, the positions of the various protons relative to the Mn(2+) ion were determined. Likewise, the water protons involved in H-bonding to neighboring residues were identified using the published, ultrahigh-resolution X-ray crystallographic coordinates of the protein (Deacon et al. J. Chem. Soc., Faraday Trans. 1997, 93(24), 4305-4312).

Binding Sites↗

PubMed2001

Elucidation of structure and location of V(IV) ions in heteropolyacid catalysts H4PVMo11O40 as studied by hyperfine sublevel correlation spectroscopy and pulsed electron nuclear double resonance at W- and X-band frequencies.

Electron spin resonance, pulsed electron nuclear double resonance (ENDOR) spectroscopy at W- and X-band frequencies, and hyperfine sublevel correlation (HYSCORE) spectroscopy have been employed to determine the location of the V(IV) ions in H4PVMo11O40 heteropolyacid catalysts. In these materials the heteropolyanions have the well-known structure of the Keggin molecule. Interactions of the unpaired electrons of the paramagnetic vanadyl ions (VO(2+)) with all relevant nuclei 1H, 31P, and 51V) could be resolved. The complete analysis of the hyperfine coupling tensor for the phosphorus nucleus in the fourth coordination sphere of the V(IV) ion allowed for the first time a detailed structural analysis of the paramagnetic ions in heteropolyacids in hydrated and dehydrated catalysts. The 31P and 1H ENDOR results show that V(IV) ions are incorporated as vanadyl pentaaqua complexes [VO(H2O)5](2+) in the void space between the heteropolyanions in the hydrated heteropolyacid. For the dehydrated H4PVMo11O40 materials the distance between the V(IV) ion and the central phosphorus atom of the Keggin molecule could be determined with high accuracy on the basis of orientation-selective 31P ENDOR experiments and HYSCORE spectroscopy. The results give a first direct experimental evidence that the paramagnetic vanadium species are not incorporated at molybdenum sites into the Keggin structure of H4PVMo11O40 and also do not act as bridges between two Keggin units after calcination of the catalyst. The vanadyl species are found to be directly attached to the Keggin molecules. The VO(2+) ions are coordinated to four or three outer oxygen atoms from one PVMo11 heteropolyanion in a trigonal-pyramidal or slightly distorted square-pyramidal coordination geometry, respectively.

Journal Article↗

PubMed2001

Copper(II) azide complexes of aliphatic and aromatic amine based tridentate ligands: novel structure, spectroscopy, and magnetic properties.

Copper(II) azide complexes of three tridentate ligands namely 2,6-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (L), 2,6-(pyrazol-1-ylmethyl)pyridine (L'), and dipropylenetriamine (dpt) yield three kinds of complexes with different azide-binding modes. The ligand L forms two end-on-end (mu-1,3) diazido-bridged binuclear complexes, [CuL(mu-N(3))](2)(ClO(4))(2) (1) and [CuL(mu-N(3))(ClO(4))](2).2CH(3)CN (2), and L' forms a perchlorato-bridged quasi-one-dimensional chain complex, [CuL'(N(3))(ClO(4))](n)() (3) with monodentate azide coordination. The ligation of dipropylenetriamine (dpt) gives a end-on (mu-1,1) diazido-bridged binuclear copper complex [Cu(dpt)(mu-N(3))](2)(ClO(4))(2) (4). The crystal and molecular structures of these complexes have been solved. Variable-temperature EPR results of 1 and 2 are identical and indicate the presence of both ferromagnetic and antiferromagnetic interactions within the dimer, the former dominating at low temperatures and the latter at high temperatures. The unusual temperature-dependent magnetic moment and EPR spectra of this dimer reveal the presence of temperature-dependent population of two triplet states, one being caused by antiferromagnetic and the other by ferromagnetic interaction, the former transforming to the latter on cooling. While the interaction of ground spin doublets of the two metal centers gives rise to a ferromagnetic coupling of J(g) = 90.73 cm(-1), the other coupling of J(e) = -185.64 cm(-1) is suggested to be caused by the interaction between an electron in one metal center and an electron from the azide of the other monomer by excitation of a d-electron to the empty ligand orbital. The ferromagnetic state is energetically favored by 104.39 cm(-1). Compound 3 exhibits axial spectra at room temperature and 77 K, and variable-temperature magnetic susceptibility data indicate that the copper centers form a weakly antiferromagnetic one-dimensional chain with J = -0.11 cm(-1). In the case of 4, the unique presence of two nonidentical dimeric units with different bond lengths and bond angles within the unit cell as inferred by crystal structure is proved by single-crystal EPR spectroscopy.

Journal Article↗

PubMed2001

35 GHz ENDOR characterization of the "very rapid" signal of xanthine oxidase reacted with 2-hydroxy-6-methylpurine (13C8): evidence against direct Mo-C8 interaction.

Xanthine oxidase is a molybdenum-containing enzyme that catalyzes the hydroxylation of xanthine and a wide variety of other aromatic heterocycles. In the course of the reaction with xanthine and substrates such as 2-hydroxy-6-methylpurine (HMP), the enzyme gives rise to a Mo(V) EPR signal, denoted "very rapid", that arises from an authentic catalytic intermediate. The two alternative catalytic mechanisms proposed for this enzyme differ critically in whether the distance between Mo and C8 of the purine nucleus in this intermediate is short enough to admit a direct bonding interaction. To examine this distance, we have performed 13C ENDOR measurements of the "very rapid" EPR signal generated by xanthine oxidase during reaction with 13C8-HMP. The resulting (13)C8 hyperfine tensor, A = [10.2(1), 7.0(1), 6.5(1)] MHz, is discussed in the framework of a detailed consideration of factors involved in extracting metrical parameters from an anisotropic hyperfine interaction composed of contributions from multiple sources, in particular, the effect of the local contributions from spin density on (13)C8. The analysis presented here gives a Mo...C distance whose value is expected to be ca. 2.7-2.9 A in the "very rapid" intermediates formed with both xanthine and HMP, consistent with plausible bond lengths for a Mo-O-C8 fragment where C8 is a trigonal-planar aromatic carbon. The difference from earlier conclusions is explained. The data thus do not support the existence of a direct Mo-C bond in the signal-giving species. This conclusion supports a mechanism that does not involve such an interaction and which begins with base-assisted nucleophilic attack of the Mo(VI)-OH group on the C-8 of substrate, with concomitant hydride transfer to the Mo=S group to give Mo(IV)-SH; the EPR-active "very rapid" species then forms by one-electron oxidation and deprotonation to yield the EPR-detectable Mo(V)OS(OR) species. We further discuss the complexities and limitations of the semiempirical method used to arrive at these conclusions.

Electron Spin Resonance Spectroscopy↗

PubMed2001

Structure of copper(II)-histidine based complexes in frozen aqueous solutions as determined from high-field pulsed electron nuclear double resonance.

W-band (95 GHz) pulsed EPR and electron-nuclear double resonance (ENDOR) spectroscopic techniques were used to determine the hyperfine couplings of different protons of Cu(II)-histidine complexes in frozen solutions. The results were then used to obtain the coordination mode of the tridentate histidine molecule and to serve as a reference for Cu(II)-histidine complexation in other, more complex systems. Cu(II) complexes with L-histidine and DL-histidine-alpha-d,beta-d2 were prepared in H2O and in D2O, and orientation-selective W-band 1H and 2H pulsed ENDOR spectra of these complexes were recorded at 4.5 K. These measurements lead to the unambiguous assignment of the signals of the H alpha, H beta, imidazole H epsilon, and the exchangeable amino, Ham, protons. The 14N superhyperfine splitting observed in the X-band EPR spectrum and the presence of only one type of H alpha and H beta protons in the W-band ENDOR spectra show that the complex is a symmetric bis complex. Its g parallel is along the molecular symmetry axis, perpendicular to the equatorial plane that consists of four coordinated nitrogens in histamine-like coordinations (NNNN). Simulations of orientation-selective ENDOR spectra provided the principal components of the protons' hyperfine interaction and the orientation of their principal axes with respect to g parallel. From the anisotropic part of the hyperfine interaction of H alpha and H beta and applying the point-dipole approximation, a structural model was derived. An unexpectedly large isotropic hyperfine coupling, 10.9 MHz, was found for H alpha. In contrast, H alpha of the Cu(II)-1-methyl-histidine complex where only the amino nitrogen is coordinated, showed a much smaller coupling. Thus, the hyperfine coupling of H alpha can serve as a signature for a histamine coordination where both the amino and imino nitrogens of the same molecule bind to the Cu(II), forming a six-membered chelating ring. Unlike H alpha the hyperfine coupling of H epsilon is not as sensitive to the presence of a coordinated amino nitrogen of the same histidine molecule.

Copper↗

PubMed2001

The effect of spin relaxation on ENDOR spectra recorded at high magnetic fields and low temperatures.

A simple theoretical model that describes the pulsed Davies electron-nuclear double resonance (ENDOR) experiment for an electron spin S = (1/2) coupled to a nuclear spin I = (1/2) was developed to account for unusual W-band (95 GHz) ENDOR effects observed at low temperatures. This model takes into account the thermal polarization along with all internal relaxation processes in a four-level system represented by the electron- and nuclear-spin relaxation times T(1e) and T(1n), respectively, and the cross-relaxation time, T(1x). It is shown that under conditions of sufficiently high thermal spin polarization, nuclei can exhibit asymmetric ENDOR spectra in two cases: the first when t(mix) >> T(1e) and T(1n), T(1x) >> T(1e), where ENDOR signals from the alpha manifold are negative and those of the beta manifold positive, and the second when the cross- and/or nuclear-relaxation times are longer than the repetition time (t(mix) << T(1e) << t(R) and T(1n), T(1x) > t(R)). In that case the polarization of the ENDOR signals becomes opposite to the previous case, the lines in the alpha manifolds are positive, and those of the beta manifold are negative. This case is more likely to be encountered experimentally because it does not require a very long mixing time and is a consequence of the saturation of the nuclear transitions. Using this model the experimental t(mix) and t(R) dependencies of the W-band (1)H ENDOR amplitudes of [Cu(imidazole)(4)]Cl(2) were reproduced and the values of T(1e) and T(1x) >> T(1e) were determined. The presence of asymmetry in the ENDOR spectrum is useful as it directly provides the sign of the hyperfine coupling. The presented model allows the experimentalist to adjust experimental parameters, such as t(mix) and t(R), in order to optimize the desired appearance of the spectrum.

Journal Article↗

PubMed2001

Experimental myocardial necrosis in rats: role of arjunolic acid on platelet aggregation, coagulation and antioxidant status.

Arjunolic acid, a new triterpene and a potent principle from the bark of Terminalia arjuna, has been shown to provide significant cardiac protection in isoproterenol induced myocardial necrosis in rats. To further explore the mechanism of action of arjunolic acid, antiplatelet activity, anticoagulant assays, electrocardiographic changes, serum marker enzymes, antioxidant status, lipid peroxide and myeloperoxidase (MPO) have been measured and the results are compared with a potent cardioprotective drug, acetyl salicylic acid (ASA). Administration of isoproterenol produces electrocardiographic changes such as decreased R amplitude and increased ST segment elevation and has resulted in an increase in serum marker enzyme levels as well as a decrease in enzymatic and nonenzymatic antioxidant levels. Arjunolic acid at an effective dosage of 15 mg/kg body wt. (pre and post treatment), when administered intraperitoneally (i.p.), effects a decrease in serum enzyme levels and the electrocardiographic changes get restored towards normalcy. Arjunolic acid treatment is also shown to prevent the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, alpha-tocopherol, reduced glutathione (GSH), ascorbic acid, lipid peroxide, MPO and the cardioprotection is confirmed by the histopathological studies. This study shows that the cardioprotection of arjunolic acid pre and post treatment could possibly be due to the protective effect against the damage caused by myocardial necrosis.

Animals↗

PubMed2000

[2,6-bis]

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Journal Article↗

PubMed1999

A W-band pulsed ENDOR spectrometer: setup and application to transition metal centers.

The design and performance of a 95 GHz pulsed W-band EPR/ENDOR spectrometer is described with emphasis on the ENDOR part. Its unique feature is the easy and fast sample exchange at 4.2 K for frozen solution and single crystal samples. In addition, the microwave bridge power output is relatively high (maximum 267 mW), which allows the application of short microwave pulses. This increases the sensitivity in echo experiments because of the broader excitation bandwidth and the possibility of employing short pulse intervals, as long as the dead time does not increase significantly with the power. The spectrometer features two microwave and radiofrequency (0.1-220 MHz, 3 kW pulse power) channels and a 6 T superconducting magnet in a solenoid configuration. The magnet is equipped with cryogenic sweep coils providing a sweep range of +/-0. 4 and +/-0.2 T for a center field of 0-4 and 4-6 T, respectively. The spectrometer performance is demonstrated on Cu(II) centers in single crystals, a zeolite polycrystalline sample, and a protein frozen solution.

Copper↗