Investigating the structural and electronic properties of nitrile hydratase model iron(III) complexes using projected unrestricted Hartree-Fock (PUHF) calculations.

Important structural and mechanistic details concerning the non-heme, low-spin Fe(III) center in nitrile hydratase (NHase) remain poorly understood. We now report projection unrestricted Hartree-Fock (PUHF) calculations on the spin preferences of a series of inorganic complexes in which Fe(III) is coordinated by a mixed set of N/S ligands. Given that many of these compounds have been prepared as models of the NHase metal center, this study has allowed us to evaluate this computational approach as a tool for future calculations on the electronic structure of the NHase Fe(III) center itself. When used in combination with the INDO/S semiempirical model, the PUHF method correctly predicts the experimentally observed spin state for 12 of the 13 Fe(III)-containing complexes studied here. The one compound for which there is disagreement between our theoretical calculations and experimental observation exhibits temperature-dependent spin behavior. In this case, the failure of the PUHF-INDO/S approach may be associated with differences between the structure of the Fe(III) complex present under the conditions used to measure the spin preference and that observed by X-ray crystallography. A preliminary analysis of the role of the N/S ligands and coordination geometry in defining the Fe(III) spin preferences in these complexes has also been undertaken by computing the electronic properties of the lowest energy Fe(III) spin states. While any detailed interpretation of our results is constrained both by the limited set of well-characterized Fe(III) complexes used in this study and by the complicated dependence of Fe(III) spin preference upon metal-ligand interactions and coordination geometry, these PUHF-INDO/S calculations support the hypothesis that the deprotonated amide nitrogens coordinating the metal stabilize the low-spin Fe(III) ground state seen in NHase. Strong evidence that the sulfur ligands exclusively define the Fe(III) spin state preference by forming metal-ligand bonds with significant covalent character is not provided by these computational studies. This might, however, reflect limitations in modeling these systems at the INDO/S level of theory.

Binuclear 1,2,4,5-tetraimino-3,6-diketocyclohexane bis[bis(bipyridine)ruthenium(II)] redox series.

The reaction of the [Ru(bpy)2(MeOH)2]2+ cation (bpy = 2,2'-bipyridine) with 1,2,4,5-tetraaminobenzene in the presence of trace water and oxygen yields the cation [(bpy)2Ru(1,2,4,5-tetraimino-3,5-diketocyclohexane)Ru(bpy)2]4+. This binuclear species undergoes ligand-based reductions, giving the 3+ and 2+ charged species. The X-ray structure, electrochemistry, ZINDO calculations, and NMR, ESR, UV/vis, and IR spectra were analyzed where possible, giving an electronic model of the binuclear species and some of its redox products. The X-ray structure reveals the [(bpy)2Ru] fragments symmetrically disposed across the 1,2,4,5-tetraimino-3,5-diketocyclohexane bridge in a molecule with Cs symmetry.

A theoretical study of the interaction of anhydrotetracycline with Al(III).

In this article the complexation of anhydrotetracycline (AHTC), the major toxic decomposition product of the antibiotic tetracycline, with Al(III) has been investigated using the AM1 semiempirical and ab initio Hartree-Fock levels of theory. Different modes of complexation have been considered with the structure of tetra- and pentacoordinated complexes being fully optimized. In the gas phase, processes ii and iii, which lead to the complexes with stoichiometry MHL2+, are favored. Structure II ([AlLH2(OH)(H2O)]2+) has the metal coordinated to the O11 and O12 groups and the O3 group protonated and is the global minimum on the potential energy surface for the interaction. In water solution, the Al(III) is predicted to form predominantly a tetracoordinated complex at the Oam and O3 site (V) of the AHTC with the stoichiometry MH2L3+ (process i). The experimental proposal is the complexed form with the metal ion coordinated to the O11-O12 moiety (site II). The intramolecular proton transfer, which leads to the most stable Al(III)-AHTC MHL2+ complex, has not been considered by the experimentalists. The experimental structure was found to be unfavorable in our calculations in both gas phase and water solution. All the semiempirical results are in perfect agreement with the ab initio calculations. So, we suggest that the experimental assignments should be revised, taking into account the results obtained in the present study.

Conformational analysis of the anhydrotetracycline molecule: a toxic decomposition product of tetracycline.

Anhydrotetracycline (AHTC) is a toxic decomposition product of the widely used antibiotic tetracycline (TC). The side effects of AHTC have been attributed to the conformational changes in the ring system. In the present study a systematic conformational analysis has been carried out using the semiempirical quantum mechanical AM1 model. The conformational pH dependence has been analyzed through the study of all the ionized species. The results obtained showed two distinct families of conformation, referred to as A and B, with the interconversion process involving a rotation around the C4a-C12a bond. The solvent effect has been considered using the continuum model COSMO. From the population analysis in the gas phase, we conclude that form A should be dominant for the LH3+ and LH2 +/- species and B is the preferred conformer for the L2- ionized form (97.54%). For the LH- derivative, we predict that both conformations should be present in the equilibrium mixture in the gas phase, with the relative concentration found to be 68.47% (A) and 31.53% (B). The inclusion of the solvent does not change the A/B equilibrium for the LH3+ and LH2 +/- species. However, for the LH- form, the equilibrium is shifted to conformer A in water solution. The population analysis in water solution for the L2- suggest the following relative concentrations: A (34.46%) and B (65.54%). The biological activity of the TC parent compound is attributed to the zwitterionic species, which should adopt a twisted conformation. According to the results obtained in the present study, the most abundant form of the LH2 +/- zwitterionic species for the AHTC molecule is the extended one (100% in both the gas phase and water solution). Therefore, from a pharmacodynamic point of view, this conformational difference should be taken into account in order to explain the toxic effects of the anhydrous derivative. Another point related to the structure-activity relationship was analyzed through the investigation of the tautomerization process LH2(0)-->LH2 +/-. The result obtained suggests that the LH2(0) tautomer should be dominant in the gas phase (nonpolar solvent) and adopt a conformation classified as B. In water solution, the tautomer LH2 +/- is present as conformer A (96%). This result is in agreement with the conformation changes involved in the tautomerization process for the OTC active derivative.