Geometrical control of the active site electronic structure of pyranopterin enzymes by metal-dithiolate folding: aldehyde oxidase

Density functional calculations on geometry-optimized oxidized (Mo(VI)) and reduced (Mo(IV)) analogues of the isolated active site of aldehyde oxidase (MOP), a member of the xanthine oxidase family of pyranopterindithiolate enzymes, show that fold angle changes of the dithiolate ligand modulate the relative metal and dithiolate contributions to the frontier redox orbitals. Proton abstraction from the equatorial aqua ligand of the oxidized Mo(VI) site also flattens the metal dithiolate fold angle. It is proposed that static and/or dynamic changes in the structure of the protein surrounding the active site can induce changes in the dithiolate fold angle and thereby provide a mechanism for electronic buffering of the redox orbital, for fine-tuning the nucleophilicity of the equatorial aqua/hydroxide ligand, and for modulating the electron-transfer regeneration of the active sites of molybdenum and tungsten enzymes via a "dithiolate folding effect".     

Ab-initio studies of fluoroxytrifluoromethane geometry and electronic structure

Ab-initio molecular orbital calculations using both minimal or STO-3G and extended or 4-31G basis sets have been applied to fluoroxytrifluormethane. Complete geometry optimizations using both basis sets have been applied to this molecule and the calculated structural parameters have been compared to the electron diffraction data. The extended basis set calculations are found to be in much better overall agreement with experiment although the minimal basis set does reproduce the angular parameters well, including the tilt angle. The barrier to the CF₃ torsion has been computed and it compares favorably with the microwave spectral value.The electronic structure of CF₃OF and some related molecules have been examined by partitioning the electrons according to the method of Mulliken. The highest occupied orbital in CF₃OF is found to be largely an O-F π * orbital and the O-F bond is also found to be the least ionic and weakest bond in the molecule. The computed dipole moment of CF₃OF agrees well with the experimental value.     

End-substitution effect on the geometry and electronic structure of oligoheterocyclics

The end-substitution effects on the geometric and electronic structures of oligoheterocyclics are systematically studied using the density functional theory. It is found that the influence of the end-substitution does not depend on the heteroatom. End-substitution plays a fine-tune effect on the geometry and the excitation state. While the influences on the conducting type (p-type or n-type) and the inter-chain charge carrier hoping channels are much different between the electron-donating –CH ₃ and electron–accepting –CN substitutions. Both molecular electrostatic potentials and charge carrier injection rates indicate that the –CH ₃/–CH ₃ substitution is beneficial to the p-type doping, while the –CN/–CN substitution is in favor of the n-type doping, which is in agreement with the experimental observations. The –CH ₃ substituted packing dimers exert similar intermolecular interactions to the unsubstituted ones. The –CN substituted packing dimers yield much stronger intermolecular interactions comparing to the –CH ₃ substituted ones. It could be anticipated that the –CN substitution would be helpful to the charge carrier hopings between chains and thereby enhance the conductivity.     

The electronic structure and geometry of HNF and HBF

The results of ab initio calculations, making use of the restricted Hartree-Foek scheme, on two radicals - HNF and the postulated species HBF - are presented. Geometry predictions made, using three different basis sets of gaussian orbitals are compared, and the bonding is discussed in terms of the Mulliken population analysis. The structure of various low-lying excited states is also considered.     

Substitution effect on the geometry and electronic structure of the ferrocene

The substitution effects on the geometry and the electronic structure of the ferrocene are systematically and comparatively studied using the density functional theory. It is found that -NH(2) and -OH substituents exert different influence on the geometry from -CH(3), -SiH(3), -PH(2), and -SH substituents. The topological analysis shows that all the C-C bonds in a-g are typical opened-shell interactions while the Fe-C bonds are typical closed-shell interactions. NBO analysis indicates that the cooperated interaction of d --> pi* and feedback pi --> d + 4s enhances the Fe-ligand interaction. The energy partitioning analysis demonstrates that the substituents with the second row elements lead to stronger iron-ligand interactions than those with the third row elements. The molecular electrostatic potential predicts that the electrophiles are expected to attack preferably the N, O, P, or S atoms in Fer-NH(2), Fer-OH, Fer-PH(2), and Fer-SH, and attack the ring C atoms in Fer-SiH(3) and Fer-CH(3). In turn, the nucleophiles are supposed to interact predominantly by attacking the hydrogen atoms. The simulated theoretical excitation spectra show that the maximum absorption peaks are red-shifted when the substituents going from second row elements to the third row elements.     

Spectroscopic and density functional studies of the red copper site in nitrosocyanin: role of the protein in determining active site geometric and electronic structure

The electronic structure of the red copper site in nitrosocyanin is defined relative to that of the well understood blue copper site of plastocyanin by using low-temperature absorption, circular dichroism, magnetic circular dichroism, resonance Raman, EPR and X-ray absorption spectroscopies, combined with DFT calculations. These studies indicate that the principal electronic structure change in the red copper site is the sigma rather than the pi donor interaction of the cysteine sulfur with the Cu 3d(x2-y2) redox active molecular orbital (RAMO). Further, MCD data show that there is an increase in ligand field strength due to an increase in coordination number, whereas resonance Raman spectra indicate a weaker Cu-S bond. The latter is supported by the S K-edge data, which demonstrate a less covalent thiolate interaction with the RAMO of nitrosocyanin at 20% relative to plastocyanin at 38%. EXAFS results give a longer Cu-S(Cys) bond distance in nitrosocyanin (2.28 A) compared to plastocyanin (2.08 A) and also show a large change in structure with reduction of the red copper site. The red copper site is the only presently known blue copper-related site with an exogenous water coordinated to the copper. Density functional calculations reproduce the experimental properties and are used to determine the specific protein structure contributions to exogenous ligand binding in red copper. The relative orientation of the CuNNS and the CuSC(beta) planes (determined by the protein sequence) is found to be key in generating an exchangeable coordination position at the red copper active site. The exogenous water ligation at the red copper active site greatly increases the reorganization energy (by approximately 1.0 eV) relative to that of the blue copper protein site, making the red site unfavorable for fast outer-sphere electron transfer, while providing an exchangeable coordination position for inner-sphere electron transfer.     

New antitumour active platinum compounds containing carboxylate ligands in trans geometry: synthesis, crystal structure and biological activity

New asymmetric trans-platinum(II) complexes, composed of an isopropylamine, an azole and two carboxylate leaving groups, are presented. The crystal and molecular structures of one of the complexes has been determined and the cytotoxicity and reactivity with 5'-guanosine monophosphate is reported. The complexes show a reduced reactivity, but no decrease in cytotoxic activity compared to their chloro-counterparts. Furthermore the complexes largely overcome cisplatin resistance, they therefore present an interesting class of antitumour active trans-platinum complexes.     

Theoretical studies on electronic structure and magnetic properties of mixed‐valence uteroferrin active site

The electronic structure and magnetic interaction of the active site of pig purple acid phosphatase (PAP, uteroferrin) were investigated using pure DFT (UBLYP) and hybrid DFT methods (UB3LYP and UB2LYP). Uteroferrin catalyzes the hydrolysis of a phosphate ester under acidic conditions and contains a binuclear iron center. The mammalian PAPs are expected to be targets for drug design of osteoporosis. Their active sites are typical examples of the Fe(II)‐Fe(III) mixed‐valence system. We studied double exchange interaction of the mixed‐valence system, using the potential energy difference between the Fe(II)‐Fe(III) and the Fe(III)‐Fe(II) states. The pathway of the antiferromagnetic coupling between Fe(III) and Fe(II) were also discussed by using chemical indices, which are evaluated by the occupation numbers of singly occupied natural orbitals. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

EPR and ligand field studies of iron superoxide dismutases and iron-substituted manganese superoxide dismutases: relationships between electronic structure of the active site and activity

The problem of metal selectivity of iron/manganese superoxide dismutases (SODs) is addressed through the electronic structures of active sites using electron paramagnetic resonance and ligand field calculations. Studies of wild-type iron(III) SOD (FeSOD) from Escherichia coli and from Methanobacterium thermoautotrophicum and iron-substituted manganese(III) SOD (Fe(sub)MnSOD) from E. coli and from Serratia marcescens are reported. EPR spectroscopy of wild-type enzymes shows transitions within all three Kramers doublets identified by their g values. From the temperature dependence of the observed transitions, the zero-field splitting is found to be negative, D = -2 +/- 0.2 cm-1. The electronic structure is typical of a distorted trigonal bipyramid, all the EPR features being reproduced by ligand field analysis. This unique and necessary electronic structure characterizes wild-type enzymes whatever their classification from the amino acid sequence into iron or manganese types, as E. coli FeSOD or M. thermoautotrophicum FeSOD. In iron-substituted manganese SODs, reduced catalytic activity is found. We describe how inhomogeneity of all reported substituted MnSODs might explain the activity decrease. EPR spectra of substituted enzymes show several overlapping components. From simulation of these spectra, one component is identified which shares the same electronic structure of the wild-type FeSODs, with the proportion depending on pH. Ligand field calculations were performed to investigate distortions of the active site geometry which induce variation of the excitation energy of the lowest quartet state. The corresponding coupling between the ground state and the excited state is found to be maximum in the geometry of the native SODs. We conjecture that such coupling should be considered in the electron-transfer process and in the contribution of the typical electronic structure of FeSOD to the activity.     

Assessment of the electronic structure of 2,2'-pyridylpyrrolides as ligands

The ligand class 2,2'-pyridylpyrrolide is surveyed, both for its structural features and its electronic structure, when attached to monovalent K, Cu, Ag, Au, and Rh. The influence of pyrrolide ring substituents is studied, as well as the question of push/pull interaction between the pyridyl and pyrrolide halves. The π donor ability of the pyrrolide is found to be less than that of an analogous phenyl. However, in contrast to the phenyl analog, the HOMO is pyrrolide π in character for pyridylpyrrolide complexes of copper and rhodium, while it is conventionally metal localized for planar, d(8) rhodium pyridylphenyl. Monovalent three-coordinate copper complexes show great deviations from Y-shaped toward T-shaped structures, including cases where the pyridyl ligand bonds only weakly.     

Optimization of the geometry and electronic structure of bridged binuclear aromatic molecules

The geometries of the molecules of (C₆H₅)₂M, where M=NH, PH, O, S, CO, CS, SO, CH=CH, CH=N, N=N, and N=NO, the diphenylamine radical cation, and the diphenylnitrogen and diphenyl nitroxide radicals have been optimized by the CNDO/2, INDO, and MINDO/3 methods, and their electronic structures have been calculated. The data obtained have been interpreted in light of the investigation of the problem of reactivity.N. G. Chernyshevskii Saratov State University. Translated from Zhurnal Strukturnoi Khimii, Vol. 32, No. 2, pp. 23–29, March–April, 1991.     

Communication between the active site and the allosteric site in class A beta-lactamases

Bacterial production of beta-lactamases, which hydrolyze beta-lactam type antibiotics, is a common antibiotic resistance mechanism. Antibiotic resistance is a high priority intervention area and one strategy to overcome resistance is to administer antibiotics with beta-lactamase inhibitors in the treatment of infectious diseases. Unfortunately, beta-lactamases are evolving at a rapid pace with new inhibitor resistant mutants emerging every day, driving the design and development of novel beta-lactamase inhibitors. Here, we examined the inhibitor recognition mechanism of two common beta-lactamases using molecular dynamics simulations. Binding of beta-lactamase inhibitor protein (BLIP) caused changes in the flexibility of regions away from the binding site. One of these regions was the H10 helix, which was previously identified to form a lid over an allosteric inhibitor binding site. Closer examination of the H10 helix using sequence and structure comparisons with other beta-lactamases revealed the presence of a highly conserved Trp229 residue, which forms a stacking interaction with two conserved proline residues. Molecular dynamics simulations on the Trp229Ala mutants of TEM-1 and SHV-1 resulted in decreased stability in the apo form, possibly due to loss of the stacking interaction as a result of the mutation. The mutant TEM-1 beta-lactamase had higher H10 fluctuations in the presence of BLIP, higher affinity to BLIP and higher cross-correlations with BLIP. Our results suggest that the H10 helix and specifically W229 are important modulators of the allosteric communication between the active site and the allosteric site.     

Molecular geometry and electronic structure of chlorosubstituted trans- and cis-stilbene derivatives

Geometrical structures of several chlorostilbenes were determined from ultraviolet absorption spectra in solution by calculations based on the simple LCAO molecular orbital method. Dipole moments were evaluated for all derivatives without a center of symmetry in the calculated geometry. The results are in good agreement with experimental data.

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Zusammenfassung Die geometrischen Strukturen einiger Chlorostilbene werden aus den UV-Absorptionsspektren in Lösung mittels einfacher MO-LCAO Berechnungen erhalten. Für alle Verbindungen, deren berechnete Struktur kein Symmetriezentrum aufweist, werden die Dipolmomente bestimmt. Die Resultate stehen in gutem Einklang mit den experimentellen Daten.

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Résumé Les structures géométriques de plusieurs chlorostilbènes ont été déterminées à partir des spectres d'absorption ultraviolette en solution par des calculs fondés sur la méthode simple des orbitales moléculaires. Pour tous les dérivés sans centre de symétrie les moments dipolaires ont été évalués à l'aide de la géométrie calculée. Les résultats sont en bon accord avec l'expérience.

     

Interrelations between charging, structure and electrokinetics of nanometric polyelectrolyte films

Streaming current, surface conductivity and swelling data of poly(acrylic acid) (PAA) and poly(ethylene imine) (PEI) thin films are analyzed on the basis of the theory for diffuse soft interfaces (J.F.L. Duval, R. Zimmermann, A. L. Cordeiro, N. Rein, C. Werner, Langmuir 25 (2009) 10691). Focus is put on ways to unravel the electroosmotic and migration contributions of the measured surface conductivity, which is crucial for appropriate electrokinetic analysis of films carrying high densities of dissociable groups. Results demonstrate that the osmotically-driven swelling of the PAA films with increasing pH is accompanied by an increase in diffuseness for the interphasial polymer segment density distribution. This heterogeneity is particularly marked at low ionic strength with a non-monotonous dependence of the streaming current on pH and the presence of a maximum at pH～6.5. The analysis of the PEI films evidences heterogeneous swelling with lowering pH, i.e. upon protonation of the amine groups. The characteristic decay length in the interphasial PEI segment density distribution is found to be nearly independent of the pH, which is in line with the moderate swelling determined by ellipsometry. A critical discussion is given on the strengths and limitations of electrokinetics/surface conductivity for quantifying the coupled electrohydrodynamic and structural properties of moderately to highly swollen polyelectrolyte thin films.     

Sharp-line electronic spectroscopy and metal-ligand geometry in chromium(III) complexes with triazacyclononane ligands

Summary An angular overlap model analysis of the sharp-line electronic spectrum of bis(triazacyclononane)chromium(III) chloride indicates that the nitrogen coordination sphere is only slightly distorted from an octahedral arrangement. The best fit to the spectrum was obtained for a geometry in which the nitrogens within a ring are displaced 1.1° away from the cartesian axes towards the molecular C₃ axis and the two rings are twisted by 3.4° away from an antiprismatic orientation. The blue-shift often observed for triazacyclononane complexes compared to complexes with other amine ligands appears not to be due to large geometric distortions in the [9]aneN₃ complexes, and in fact the nitrogen ligand field strengths in [9]aneN₃ and ethylenediamine complexes are not very different when geometric distortions in both complexes are accounted for. A similar analysis of the sharp-line spectrum of triazacylononanetriacetatochromium(III) was undertaken, making use of the known ligand geometry. The ligand field strength of the nitrogens is significantly smaller for this ligand because of inductive effects from the acetato groups. The acetato ligands are strong - and -donors.     

Photoelectron spectra,electronic and spatial structure of phenylhydrazones

Theoretical and Experimental Chemistry -     

Discrimination between enantioselective and non-selective binding sites on cellobiohydrolase-based stationary phases by site specific competing ligands.

A systematic study was performed to investigate the influence of cellobiose or lactose on the enantioselective retention behaviour of some beta-blockers in liquid chromatography using Cellobiohydrolase (CHB) I from Trichoderma reesei or Cellobiohydrolase 58 from Phanerochaete chrysosporium immobilized on silica as stationary phases. The results revealed that the retention could be described by the function [equation; see text] where the observed capacity factor corresponds to the sum of an enantioselective mode being influenced by a site specific competing ligand (competitor) and a non-selective mode unaffected by the competitor. A non-constrained non-linear least-square regression gave in all cases virtually identical nondisplacable capacity factors (k'ns) for both enantiomers of the same drug. The experimental capacity factors (k'(x,C)) of the enantiomers all show a close fit to the adapted function. The Kd values calculated for the competitor were also virtually identical for each pair of enantiomers and were in accordance with Ki data determined for the competitors in classical enzyme kinetics experiments, demonstrating that one unique site; namely, the catalytic site, was responsible for the enantioselective binding. Similar results were obtained with the resolution of rac-alprenolol and rac-metoprolol on CBH I phase.     

Sulfur K-edge XAS and DFT calculations on nitrile hydratase: geometric and electronic structure of the non-heme iron active site

The geometric and electronic structure of the active site of the non-heme iron enzyme nitrile hydratase (NHase) is studied using sulfur K-edge XAS and DFT calculations. Using thiolate (RS(-))-, sulfenate (RSO(-))-, and sulfinate (RSO(2)(-))-ligated model complexes to provide benchmark spectral parameters, the results show that the S K-edge XAS is sensitive to the oxidation state of S-containing ligands and that the spectrum of the RSO(-) species changes upon protonation as the S-O bond is elongated (by approximately 0.1 A). These signature features are used to identify the three cysteine residues coordinated to the low-spin Fe(III) in the active site of NHase as CysS(-), CysSOH, and CysSO(2)(-) both in the NO-bound inactive form and in the photolyzed active form. These results are correlated to geometry-optimized DFT calculations. The pre-edge region of the X-ray absorption spectrum is sensitive to the Z(eff) of the Fe and reveals that the Fe in [FeNO](6) NHase species has a Z(eff) very similar to that of its photolyzed Fe(III) counterpart. DFT calculations reveal that this results from the strong pi back-bonding into the pi antibonding orbital of NO, which shifts significant charge from the formally t(2)(6) low-spin metal to the coordinated NO.