MO-Studies of enzyme reaction mechanisms. I. Model molecular orbital study of the cleavage of peptides by carboxypeptidase A

Ab initio and semiempiridal (AM1) molecular orbital theory has been used to model the cleavage of formamide at the active site of carboxypeptidase A. The model active site consists of a zinc dication coordinated to two imidazoles, an acetate, a water with a hydrogen-bonded formate, and a formamide molecule as model substrate. AM1 has been compared with ab initio theory for the coordination of water and formamide to Zn⁺⁺ and found to give excellent energetic results. The course of the amide cleavage was therefore calculated with AM1. The first step of the reaction is the dissociation of the zinc-coordinated water to give an active ZnOH⁺ species. The remote formate acts as proton acceptor. This process has an activation energy of only 4.6 kcal mol^?1. The next and rate-determining step is the concerted addition of the ZnOH⁺ moiety to the formamide C?O bond. The Zn? O distance in the transition state is more than 3 Å. In four further steps, the amide nitrogen is protonated and the C? N bond cleaved. The net activation energy for the entire process is 15.5 kcal mol^?1 relative to the active site model and 19.6 kcal mol^?1 relative to the most stable point on the calculated reaction profile.     

O?H stretching force constant in associated methanol species and the cooperativity effect

The effect of molecular interaction on the O? H stretching force constant of methanol (MeOH) is reported for its associated species. The various electron donors (D) and acceptors (A) considered include organic molecules such as methanol, dimethylether, acetone, acetonitrile, dimethyl formamide, pyridine, and ions such as F^?, Cl^?, Li⁺, and H⁺. The variation in the O? H stretching force constant of MeO? H…?D species on interaction with the electron acceptor such as in the species is explained on the basis of the cooperativity effect. (CE ). The effect is discussed in terms of the relationship CE = (ΔF/F) × 100, where ΔF is the reduction is force constant of the hydrogen-bonded O? H stretching mode of the associated methanol species MeOH…?D when the lone pair electrons on oxygen of the methanol molecule are involved in hydrogen bonding with A, and F is the hydrogen-bonded O? H stretching force constant of the species when the lone pair electrons are free. The cooperativity effect (CE ) is found to increase with increasing electron acceptor and electron donor capacities of A and D. The calculated force constants are compared with the experimental results.     

Electron transfer. 121. Oxidations by Rhodium-Bound Superoxide

The violet superoxo complex, [(H₂O)₄(OH)Rh^III(O₂)Rh^III(OH)(H₂O)₄]³⁺, formed by treatment of (Rh^II)₂⁴⁺ with O₂ in HClO₄, is converted to a le^? reduction product, the corresponding μ-peroxo complex, by the reductants I^?, IrCl₆^3?, and the trinuclear aquamolybdenum(III) cation, (Mo^III)₃. Each reaction is first-order in both redox partners, and the le^? reduction by IrCl₆^3? is followed by a much slower conversion to a peroxide-free complex. Among the rapid reductions of the superoxo derivative examined here and in a previous study, only that by IrCl₆^3? is accelerated by increases in acidity; the rate law for this reaction features both an acid-independent and a [H⁺]-proportional component, the latter stemming from partial conversion of the oxidant to its conjugate acid (pK_A < ?1.0). Rate laws for reductions by other metal-center reagents generally exhibit inverse-[H⁺] terms, reflecting deprotonation of the reductant. All reductions thus far observed involving this superoxo species appear to be outer-sphere. Treatment of acid-independent rate constants within the framework of the Marcus model, allows estimates of the self-exchange rate, k₁₁, for the (Rh^III)₂-bound superoxo-peroxo couple. Because values of k₁₁ calculated from the several reductions span a range of 10^4.5, reductions of the superoxo complex cannot be taken to conform satisfactorily to the Marcus treatment, being in this respect comparable to the systems VO(OH)^+/2+, Mn^2+/3+, Eu^2+/3+, and Ti(OH)^2+/3+, each of which exhibits similar divergences. The wide range of calculated self-exchange rates appears to invalidate an earlier suggestion that reduction of the superoxo complex by Fe²⁺ proceeds primarily through a bridged path. © 1994 John Wiley & Sons, Inc.     

One-bond 1J(15N,H) coupling constants at sp2-hybridized nitrogen of Schiff bases,enaminones and similar compounds: A theoretical study

¹J(¹⁵N,H) coupling constants for enaminones and NH-forms of intramolecularly hydrogen-bonded Schiff bases as model compounds for sp²-hybridized nitrogen atoms are evaluated using density functional theory (DFT) to find the optimal functionals and basis sets. Ammonia is used as a test molecule and its one-bond coupling constant is compared with experiment. A methylamine Schiff base of a truncated molecule of gossypol is used for checking the performance of selected B3LYP, O3LYP, PBE, BHandH, and APFD density functionals and standard, modified, and dedicated basis sets for coupling constants. Both in vacuum and in chloroform, modeled by the simple continuum model of solvent, the modified basis sets predict significantly better the ¹J(¹⁵N,H) value in ammonia and in the methylamine Schiff base of a truncated molecule of gossypol than the standard basis sets. This procure is then used on a broad set of intramolecularly hydrogen-bonded molecules, and a good correlation between calculated and experimental one-bond NH coupling constants is obtained. The ¹J(¹⁵N,H) couplings are slightly overestimated. The calculated data show for hydrogen-bonded NH interatomic distances that the calculated values depend on the NH bond lengths. The shorter the bond lengths, the larger the ¹J(¹⁵N,H). A useful correlation between ¹J(¹⁵N,H) and NH bond length is derived that enables realistic predictions of one-bond NH coupling constants. The calculations reproduce experimentally observed trends for the studied molecules.     

Mesophase behaviour of azobenzene-based angular supramolecular hydrogen-bonded liquid crystals

New types of angular 1:1 hydrogen-bonded supramolecular complexes via hydrogen-bond formation between 4-alkoxyphenylazo benzoic acids (In) and 4-(3?-pyridylazo)-4??-alkoxybenzoates (IIm) with various alkoxy chains (from 6 to 16 carbons) were prepared and investigated for their mesophase behaviour by differential scanning calorimetry (DSC) and polarised-light microscopy (PLM). All prepared homologues were found to be dimorphic, possessing smectic C and nematic mesophases. The formation of 1:1 hydrogen-bonded supramolecular liquid crystals (LCs) complexes was confirmed by FTIR and UV?visible (UV?vis) absorption spectroscopy. The study revealed that nematic transition enhancement (ΔT) decreases with the increase of the alkoxy chain length on the base complement, while it increases with the increase of the chain attached to the acid complement of the complex, that is the stability of the nematic phase is more dependent on the length of the acid component.     

Density Functional Theory calculations on the magnetic properties of the model tyrosine radical-histidine complex mimicking tyrosyl radical Y<Subscript>D</Subscript><Superscript>·</Superscript> in photosystem II

Results of Density Functional Theory (DFT) theoretical investigations, which use a model tyrosyl (Tyr) radical and tyrosyl-histidine (Tyr-His) complex to mimick the Y _D ^· radical in Photosystem II (PSII) are presented and compared to experimental results from ¹⁵N Electron-Nuclear Double Resonance spectroscopy (ENDOR) studies of the τ nitrogen coupling from His-189 in the PSII Tyr-His complex. The DFT calculations are performed using an optimized geometry of the tyrosine radical and Tyr-His complex. The conformational space of the Tyr-His tandem is explored by varying the relative geometry of the two components; relevant parameters, such as the spin distribution on the phenoxy-ring carbons of the Tyr radical and the EPR hyperfine tensors, are calculated at each geometry and compared with the available experimental data. The isotropic ¹⁵N-ENDOR signal arising from spin delocalization on the His hydrogen-bonded to the PSII tyrosine radical is analyzed in terms of the DFT obtained parameters. The calculations of the g tensor using the Gauge Independent Atomic Orbital (GIAO) approach are presented and the influence of the geometry of the Tyr-His complex on the deviation of the g-tensor elements from the free electron values is discussed.     

Spectroscopic investigations of hematoxylin–Eu(III) complex interacting with Herring-sperm DNA

The interaction of HE–Eu(III) complex (HE?=?hematoxylin) with Herring-sperm DNA (hsDNA) has been studied by absorption spectra, fluorescence, and viscosity measurements in physiological buffer (pH?=?7.40). The binding constant of HE–Eu(III) complex to hsDNA was obtained by double reciprocal method at 298 and 310?K and the corresponding thermodynamic parameters (Δ_r Hm??=?8.55?×?10⁴?J?mol^?1, Δ_r Gm??=??3.01?×?10⁴?J?mol^?1, Δ_r Sm??=?387.95?J?mol^?1?K^?1) were calculated, showing that the interaction between HE–Eu(III) complex and hsDNA was driven mainly by entropy. The value of K indicated that the binding mode of HE–Eu(III) complex with DNA was not classical intercalation. These results were further supported by viscosity method and competitive binding experiment. Scatchard analysis suggests that the interaction mode was a mixed binding, which contains partial intercalation and groove binding.     

C?H bonds with a Positive Dipole Gradient Can Form Blue‐Shifting Hydrogen Bonds: The Complex of Halothane with Methyl Fluoride

The complex of halothane (CF₃CBrClH) with ([D₃])methyl fluoride is investigated theoretically by means of ab initio calculations at the MP2/6‐311++G(d,p) level and experimentally by infrared spectroscopy of solutions in liquid krypton. The complexation energy is calculated to be ?12.5 kJ mol^?1. The dipole moment of halothane monomer as a function of the C? H stretching coordinate is calculated with different methodologies and the value of (?μ/?Q₁)₀ is found to be positive. In the spectra, formation of a 1:1 complex is observed. The standard complexation enthalpy is measured to be ?8.4(2) kJ mol^?1. The C? H stretching vibration of halothane shows a blueshift of +15.4 cm^?1 on complexation, and its infrared intensity ratio ε_complex/ε_monomer is found to be 1.39(7). The frequency shift is analyzed by a Morokuma analysis, and the infrared intensities are rationalized by using a model which includes the mechanical and electrical anharmonicity of the C? H stretching vibration.     

Properties of strong hydrogen-bonded systems: The formation of hydrogen-bonded ion pair in amine·HCL systems

The hydrogen-bonded complexes between CH₃NH₂ and (CH₃)₂NH with HCl have been studied by the ab initio molecular orbital method using the 4–31G basis set. Calculations show that the proton potential curve has a single minimum near to the nitrogen atom in both complexes. This means that the proton has been transferred from HCl to the amine. ΔE and the dipole moment of the complexes studied are as follows: ?18.2 kcal mol^?1, 10.3 D for methylamine ·HCl, and ?21.7 kcal mol^?1 11.1 D for the corresponding dimethylamine complex. Other properties of the hydrogen-bonded ion pairs are discussed.     

Energetics and electronic rearrangements of proton transfer in (H3NHOH2)+

Proton transfer between N and O in the hydrogen-bonded system (H₃NHOH₂)⁺ is studied by ab initio molecular orbital methods. Potential energy curves are calculated at the hartree–Fock level using the 4–31G basis set for hydrogen bond lengths R(NO) varying from the equilibrium value of 2.664 to 3.10 Å. Short hydrogen bonds are associated with asymmetric single-well potentials in which the minimum corresponds to the NH? O configuration. For longer R(NO) separations, the potential is of double-well form, including both N? HO and NH? O as minima. It is found that the height of the energy barrier to proton transfer is sensitive to both stretches and bends of the hydrogen bond. Continuous changes in the electron density are monitored at various stages of proton transfer via density difference maps and Mulliken population analyses. The initial loss of density from the proton-accepting molecule during the first half of the transfer is accelerated during the second half. A correlation is drawn between the energetics of transfer in a number of systems and the net charge lost by the proton-acceptor group.     

Intermolecular Interactions in Li+‐glyme and Li+‐glyme–TFSA− Complexes: Relationship with Physicochemical Properties of [Li(glyme)][TFSA] Ionic Liquids

The stabilization energies (ΔE_form) calculated for the formation of the Li⁺ complexes with mono‐, di‐ tri‐ and tetra‐glyme (G1, G2, G3 and G4) at the MP2/6‐311G** level were ?61.0, ?79.5, ?95.6 and ?107.7 kcal mol^?1, respectively. The electrostatic and induction interactions are the major sources of the attraction in the complexes. Although the ΔE_form increases by the increase of the number of the O???Li contact, the ΔE_form per oxygen atom decreases. The negative charge on the oxygen atom that has contact with the Li⁺ weakens the attractive electrostatic and induction interactions of other oxygen atoms with the Li⁺. The binding energies calculated for the [Li(glyme)]⁺ complexes with TFSA^? anion (glyme=G1, G2, G3, and G4) were ?106.5, ?93.7, ?82.8, and ?70.0 kcal mol^?1, respectively. The binding energies for the complexes are significantly smaller than that for the Li⁺ with the TFSA^? anion. The binding energy decreases by the increase of the glyme chain length. The weak attraction between the [Li(glyme)]⁺ complex (glyme=G3 and G4) and TFSA^? anion is one of the causes of the fast diffusion of the [Li(glyme)]⁺ complex in the mixture of the glyme and the Li salt in spite of the large size of the [Li(glyme)]⁺ complex. The HOMO energy level of glyme in the [Li(glyme)]⁺ complex is significantly lower than that of isolated glyme, which shows that the interaction of the Li⁺ with the oxygen atoms of glyme increases the oxidative stability of the glyme.     

Investigation of aromatic hydroxyoxime-transition metal complexes by infrared spectroscopy

The preparation and infrared spectroscopic studies of coordination compounds of salicylaldoxime, 2-hydroxy-acetophenone oxime, 2-hydroxy-benzophenone oxime and 2-hydroxy-4-methoxy-benzophenone oxime with copper (II), nickel (II), cobalt (II) and iron (II) are described. The frequency of the C=N stretching vibration is usually higher in the complex than that in the ligand. The higher this frequency is, the larger the stability constant of the complex will be, but there is no quantitative relationship. In the case of complexes of salicylaldoxime with Cu (II), Ni (II), Co (II) and Fe (II), v_O=N values are correlated linearly with the ionization potentials of the central metal ions. The frequency of the OH stretching vibration is closely related to the geometric configuration of the complex. Thus aromatic hydroxyoximes form coordination compounds with Co (II) and Fe (II) with cis configuration possessing six-membered hydrogen-bonded ring. This is indicated in the infrared spectra by the complete absence of the OH stretching band, or by the appearance of an extremely broad and flat band of very low intensity. However, Cu (II) or Ni (II) complex possesses trans configuration with five-membered hydrogen-bonded bridge showing characteristic OH absorption band in the infrared region. The v_oh's of complexes investigated are closely related to the polar nature of substituents on the benzene ring. By examining the spectra of ⁶³Cu and ⁶⁵Cu complexes with 2-hydroxy-4(5)-substituted benzophenone oximes in the far infrared region, the characteristic frequency of M-O and M-N were assigned for a series of aromatic hydroxyoxime-transition metal complexes.     

Treatment of hydrogen bonding within CNDO/2 and MINDO/3: CNDO/2H and MINDO/3H

A formalism has been developed to treat hydrogen-bonded A—H…?B systems within the CNDO /2 and the MINDO /3 methodologies. In this formalism the interactions are divided into three distinct classes; those between (a) two hydrogen-bonded atoms, (b) one hydrogen-bonded and non-hydrogen-bonded atom, and (c) two non-hydrogen-bonded atoms. The last class of interactions is treated solely by the existing CNDO /2 or MINDO /3 method. For A –H…?B systems, the core resonance integrals are individually parametrized depending upon the class of the interaction. Three types of A—H…?B systems have been thus far parametrized. Nine hydrogen-bonded dimers have been studied using the new formalism and the current CNDO /2 and the MINDO /3 methods. MINDO /3 predicts very large interatomic (A –B) distances for the equilibrium geometry, and relatively small stabilization values for the hydrogen-bond energies. CNDO/2 predicts the reverse. The new formalism for both CNDO /2 and MINDO /3 predicts accurate geometries as well as energies for all nine dimers. The new formalisms are called CNDO /2H and MINDO /3H. A general discussion of the nature of hydrogen bonding as exhibited by CNDO /2H and MINDO /3H is presented.     

Metallkomplexe mit Tetrapyrrol-Liganden. 68. Synthese wasserlöslicher Osmium-Porphyrin-Komplexe

Metal Complexes with Tetrapyrrole Ligands. 68. Synthesis of Water-Soluble Osmium Porphyrin Complexes The synthesis of osmium tetraphenylporphyrinates with functional groups in the para-position of the phenyl rings is described. By sulfonation of the corresponding para-unsubstituted complex the carbonylosmium(II)-complex [OsCO(TPPS₄)H₂O]^4? or the dioxoosmium(VI)-complex [OsO₂(TPPS₄)]^4? [(TPPS₄)^6?: hexa-anion of tetrakis(4-sulfonatophenyl)porphyrin] is obtained. The osmochrome complex [Os(TPPS₄)(1-Meim)₂]^4?, which changes to the osmichrome complex [Os(TPPS₄)(1-Meim)₂]^3? in the presence of air, is formed from the dioxo-compound by reduction. These anions are deposited as water-soluble sodium- or as water-insoluble tetraphenylarsonium salts. The novel osmochrome complex Os(TMeCPP)(1-Meim)₂ (TMeCPP)^2?: [dianion of tetrakis(4-methoxycarbonylphenyl)porphyrin] is transformed by alcaline saponification and precipitation with hydrochloric acid to the corresponding alcali-soluble osmochrome tetracarbonic acid Os(TH₄CPP)(1-Meim)₂. UV/Vis-, ¹H-NMR-spectra and electrophoreses provide insight into the behaviour of the osmiumporphyrinate anions in water.     

Rapid determination of liquid-vapor equilibria. 2,2,2-Trifluoroethanol +tetrahydrofuran at 298.15 K

An automated vapor-pressure apparatus designed in this laboratory has been used to obtain liquid-vapor equilibria for 2,2,2-trifluoroethanol + tetrahydrofuran at 298.15 K. Curves of vapor pressure against composition (liquidus and vapor lines) are inferred from pressures and total compositions, using activity-coefficient expansions consistent with the Gibbs-Duhem equation. Deviations from vapor-phase ideality have been attributed to formation of a 1—1 hydrogen-bonded complex between trifluoroethanol and tetrahydrofuran, for which an association constant of 55 dm³ mol^?1 is calculated. The experimental and computational methods described can yield accurate liquid-vapor equilibrium results in a fraction of the time required for conventional recirculating-still experiments.     

A Theoretical Study of Complex Formation between Formaldehyde and Lithium

Ab initio SCF and CI calculations on the cationic and neutral complexes of formaldehyde and lithium are reported. For the cationic complex CH₂O/Li⁺, the stabilization energy of 41.7 kcal/mol obtained from the SCF calculation increases to 51.6 kcal/mol if a configuration interaction is introduced. For the neutral complex CH₂O^?/Li⁺, the C_2v-conformer of the ²A₁-state with the equilibrium bond distances of d(C? O) = 1.23 Å and d (O? Li) = 1.90 Å is calculated to be more stable than the ₂B₁-state with d (C? O) = 1.34 Å, and d (O? Li) = 1.65 Å. Charge transfer and polarization effects upon complex formation are discussed.     

Hyperpolarizabilities of hydrogen-bonded complexes of phenol derivatives with ammonia: PM3 and ab initio studies

Polarizability and first hyperpolarizability values of the hydrogen-bonded complexes formed by nitrosubstituted phenols with ammonia have been calculated using PM3 and ab initio (STO-3G) methods. It has been shown that enhancement of the polarizability (Δα) as well as the first hyperpolarizability (Δβ) of the complex arises from the hydrogen bond interaction between the phenol derivative and ammonia.     

Crystal structure,DNA interaction,and antiproliferative activity of the cobalt(II) complex of demethylcantharate and imidazole

A new cobalt(II) complex, [Co(C₃H₄N₂)(C₈H₈O₅)(H₂O)₂]·2H₂O, of demethylcantharate(7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C₈H₈O₅) with imidazole has been synthesized from cobalt chloride, demethylcantharidin (NCTD) and imidazole. The complex was characterized by elemental analysis, IR, and X-ray single crystal diffraction. The complex crystallized in the monoclinic crystal system and P2₁/m space group with a?=?0.634790(10)?nm, b?=?0.963030(10)?nm, c?=?1.221770(10)?nm, α?=?90°, β?=?95.9700(10)°, γ?=?90°, V?=?0.742844(15)?nm³, M_r ?=?383.22, D_c ?=?1.713?g?cm^?3, Z?=?2, F(0?0?0)?=?398, μ?=?1.206?mm^?1, the final R?=?0.0291, and wR?=?0.0837 [I?>?2σ(I?)]. The interaction of the complex with deoxyribonucleic acid (DNA) was studied by electronic absorption spectra, fluorescence spectra, and viscosity measurements, which indicate that the complex binds to calf thymus DNA through a partially intercalative mode. The binding constant K _b for the complex was 2.62?×?10⁴?L?mol^?1. The antiproliferation activity test showed that the complex has high antiproliferative ability against human hepatoma cells SMMC7721 (with IC₅₀ being 42.8?±?0.9?µmol?L^?1) and human lung cancer cells A549 (with IC₅₀ being 65.1?±?3.2?µmol?L^?1). The inhibition rates of the complex are much higher than those of NCTD.     

Iron(III)‐Complexes Engaged in the Biochemical Processes in Seawater. I. Voltammetry of Fe(III)‐Succinate Complexes in Model Aqueous Solution

Fe³⁺ complexes with succinic acid, a ligand naturally present in seawater, were investigated in aqueous solutions by square‐wave and cyclic voltammetry. [Fe(suc)₂(OH)₂] and [Fe(suc)₃] were detected at potentials ?0.22 and ?0.37 V, depending on C_suc in the ranges from 0.01 to 0.07 and 0.1 to 0.5 mol L^?1, respectively. Redox processes were irreversible, first with reactant adsorption and second diffusion controlled, both accompanied by chemical step. By UV/Vis spectra formation of these complexes was confirmed and equilibrium constant Fe(suc)₂(OH)₂?Fe(suc)₃ calculated (logK_2?3=(1.14±0.15) mol^?1 L), as well as their perceptible stoichiometry. With NTA as competing ligand, conditional stability constant of [Fe(suc)₂(OH)₂] complex was calculated (β^cond=(3.1±1.3)×10²² mol^?1 L).     

Synthesis, structure and spectral characterisation of a hydrogen-bonded polymeric manganese(III) Schiff base complex

A new hydrogen-bonded polymeric Mn(III) complex C₁₉H₂₀Mn₁N₃O₃S₁ (1) has been synthesised by conventional procedure with a new Schiff base ligand (2Z,3Z)-N ¹,N ²-bis(1-(2-hydroxyphenyl)ethylidene)ethane-1,2-diamine (H ₂ L) bearing a tetradentate N₂O₂ donor site. The complex has been characterised with several spectroscopic techniques like FT-IR, UV/Vis and EPR and also well supported by variable temperature magnetic susceptibility study. The structure of the co-ordination complex has been unequivocally confirmed from single crystal X-ray diffraction study. The redox stability of the metal chelate complex has been investigated with a slow scan cyclic voltammetry.