DFT studies on isomerization reactions in the copolymerization of ethylene and methyl acrylate catalyzed by Ni-diimine and Pd-diimine complexes

Gradient corrected density functional theory (DFT) has been used to investigate the isomerization reactions in the process of the ethylene/methyl acrylate copolymerization catalyzed by Pd-dimine and Ni-dimine complexes, modeled by a generic system NN–M–(CH₃)⁺ ; NN=–N(H)-C(H)-C(H)-N(H)-. The influence of the polar group and of the metal on the isomerization mechanism was studied. The results show that for the Pd-catalyst the isomerization follows the standard mechanism observed in homopolymerization processes, with the -hydrogen-transfer to the metal and formation of a -olefin–hydride complex. Electron withdrawing character of the polar group results in an increase of the hydride energy and the isomerization barrier. For the Ni-catalyst the overall isomerization picture is modified by the formation of a -olefin–hydride complex, in which the olefin is coordinated to the metal by the oxygen atom of the polar group. Such a -olefin–hydride is lower in energy for the Ni catalyst than the -olefin–hydride complex by 9.6 kcal mol^–1 . The latter is preferred by 2.6 kcal mol^–1 for the Pd-based system. The calculated isomerization barriers are 20.9 and 24.0 kcal mol^–1 (with respect to the initial 4-member chelate) for the Pd-catalyst and Ni-catalyst, respectively. This can result in a larger fraction of ester group directly connected to the copolymer backbone observed experimentally for the Ni-catalyst.Figure: Structure of the four-membered and five-membered chelates formed after 2,1-insertion of methyl acrylate into the metal–alkyl bond of the catalyst.     

Thermodynamics of the Binding of Chymotrypsin with the Black-eyed Pea Trypsin and Chymotrypsin Inhibitor (BTCI)

The binding of -chymotrypsin to black-eyed pea trypsin/chymotrypsin inhibitor (BTCI) has been studied using the inhibitory activity against the enzyme and the formation of the complex enzyme/inhibitor followed by measurements of fluorescence polarization. Apparent equilibrium constants were estimated for several temperatures and the values obtained range from 0.32 × 10⁷ to 1.36 × 10⁷ M^–1. The following values were found from van't Hoff plots: H _vh ^° = 10.8 kcal mol^-1 (from inhibitory assays) and 11.1 kcal mol^–1 (from fluorescence polarization); S° = 67.9 and = 67.8 kcal K^–1 mol^–1, respectively. Calorimetric binding enthalpy was determined (corrected for the ionization heat of the buffer) and the resulting value was H _cal ^° = 4.9 kcal mol^-1. These results indicate that the binding of chymotrypsin to BTCI is an entropically driven process.     

Modeling of the mechanism of nucleophilic aromatic substitution of fungicide chlorothalonil by glutathione

Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile, TCIN, CAS 1897-45-6) is a broad range spectrum fungicide whose fungitoxic action has been associated with the rapid formation of conjugated chlorothalonil–cellular thiol derivatives, specifically with thiol-rich enzymes such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and with glutathione (GSH). The biotransformation reaction sequence between enzyme-activated glutathione (GSH) and chlorothalonil depletes cellular glutathione reserves. The conjugation of glutathione with chlorothalonil via nucleophilic aromatic substitution was modeled for an isolated reacting species using semiempirical self-consistent field molecular orbital (SCF-MO) theory at the PM3 level. The potential energy hypersurface at each of the three possible chlorinated attack sites on chlorothalonil was elaborated using a thiolate (CH₃S^–) anion as a model for an enzyme-activated glutathione molecule. Calculated free energies of activation for formation of mono-RSH conjugates suggest that the order of nucleophilic attack on chlorine positions in TCIN is 2>4, 6>5 although energy differences are small (on the order of 1–2 kcal mol^–1). Meisenheimer or -complexes have been isolated as true intermediates on the hypersurface for each reaction, suggesting that the mechanism follows a two-step pathway.Electronic Supplementary Material available.     

Molecular dynamics simulations of void defects in the energetic material HMX

A molecular dynamics (MD) simulation was carried out to characterize the dynamic evolution of void defects in crystalline octahydro-1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine (HMX). Different models were constructed with the same concentration of vacancies (10 %) to discuss the size effects of void. Energetic ground state properties were determined by annealing simulations. The void formation energy per molecule removed was found to be 55–63 kcal/mol^?1, and the average binding energy per molecule was between 32 and 34 kcal/mol^?1 according to the change in void size. Voids with larger size had lower formation energy. Local binding energies for molecules directly on the void surface decreased greatly compared to those in defect-free lattice, and then gradually increased until the distance away from the void surface was around 10 Å. Analysis of 1 ns MD simulations revealed that the larger the void size, the easier is void collapse. Mean square displacements (MSDs) showed that HMX molecules that had collapsed into void present liquid structure characteristics. Four unique low-energy conformers were found for HMX molecules in void: two whose conformational geometries corresponded closely to those found in HMX polymorphs and two, additional, lower energy conformers that were not seen in the crystalline phases. The ratio of different conformers changed with the simulated temperature, in that the ratio of α conformer increased with the increase in temperature.     

Theoretical studies of the interaction between enflurane and water

Increase of the atmospheric concentration of halogenated organic compounds is partially responsible for a change of the global climate. In this work we have investigated the interaction between halogenated ether and water, which is one of the most important constituent of the atmosphere. The structures of the complexes formed by the two most stable conformers of enflurane (a volatile anaesthetic) with one and two water molecules were calculated by means of the counterpoise CP-corrected gradient optimization at the MP2/6–311++G(d,p) level. In these complexes the CH…O_w hydrogen bonds are formed, with the H…O_w distances varying between 2.23 and 2.32 Å. A small contraction of the CH bonds and the blue shifts of the ν(CH) stretching vibrations are predicted. There is also a weak interaction between one of the F atoms and the H atom of water, with the H_w…F distances between 2.41 and 2.87 Å. The CCSD(T)/CBS calculated stabilization energies in these complexes are between ?5.89 and ?4.66 kcal?mol^?1, while the enthalpies of formation are between ?4.35 and ?3.22 kcal?mol^?1. The Cl halogen bonding between enflurane and water has been found in two complexes. The intermolecular (Cl···O) distance is smaller than the sum of the corresponding van der Waals radii. The CCSD(T)/CBS stabilization energies for these complexes are about ?2 kcal?mol^?1.

Changes of primary sequence and secondary structure proximal to the 5′ end of the stop codon substantially increases the expression of the variable region of an antibody in <Emphasis Type="Italic">E. coli</Emphasis>

The sequence context at the 5 end of the stop codon may influence the efficiency of termination and translation. To increase the expression of a designed variable region of an antibody (named as VH5) against tumor necrosis factor (TNF), two nucleotides (TC) at 25 and 26 nucleotides (nt) upstream of termination codon were substituted with AG, respectively. The free energy of 70 nt (arbitrarily defined from the 32 nt upstream of termination codon to 38 nt downstream) was changed from –13.5 kcal mol^-1 to –17.3 kcal mol^-1. The expression level was increased from 1 ± 0.3% to 10 ± 1.2% of total cellular protein. Although the precise mechanism of this phenomenon remains to be elucidated, this report provides an alternative means to increase the expression of a foreign gene in E. coli. Revisions requested 18 October 2004; Revisions received 26 November 2004     

Stacking Interactions between Carbohydrate and Protein Quantified by Combination of Theoretical and Experimental Methods

Carbohydrate – receptor interactions are an integral part of biological events. They play an important role in many cellular processes, such as cell-cell adhesion, cell differentiation and in-cell signaling. Carbohydrates can interact with a receptor by using several types of intermolecular interactions. One of the most important is the interaction of a carbohydrate''s apolar part with aromatic amino acid residues, known as dispersion interaction or CH/π interaction. In the study presented here, we attempted for the first time to quantify how the CH/π interaction contributes to a more general carbohydrate - protein interaction. We used a combined experimental approach, creating single and double point mutants with high level computational methods, and applied both to Ralstonia solanacearum (RSL) lectin complexes with α-l-Me-fucoside. Experimentally measured binding affinities were compared with computed carbohydrate-aromatic amino acid residue interaction energies. Experimental binding affinities for the RSL wild type, phenylalanine and alanine mutants were −8.5, −7.1 and −4.1 kcal.mol⁻¹, respectively. These affinities agree with the computed dispersion interaction energy between carbohydrate and aromatic amino acid residues for RSL wild type and phenylalanine, with values −8.8, −7.9 kcal.mol⁻¹, excluding the alanine mutant where the interaction energy was −0.9 kcal.mol⁻¹. Molecular dynamics simulations show that discrepancy can be caused by creation of a new hydrogen bond between the α-l-Me-fucoside and RSL. Observed results suggest that in this and similar cases the carbohydrate-receptor interaction can be driven mainly by a dispersion interaction.     

Technical communication: Determination of cuprous ions in bacterial leachates and for environmental monitoring

A sensitive and precise spectrophotometric method has been developed for the determination of copper(I) in bacterial leach liquors produced by the action of Thiobacillus ferrooxidans and T. thiooxidans on copper ores. In this method bicinchoninic acid (BCA) has been used as the chromogenic reagent which produces a stable purple complex with Cu(I) which was found to obey Beer's Law and with _max at 560 nm. The coloured complex has a molar extinction coefficient () value of 6.6 × 10³ l mol^–1 cm^–1; specific absorptivity () value of 0.104 ml^–1 g cm^–1 and the Sandell sensitivity (S) value was 0.0096 g cm². Optimal conditions for development of coloration/sensitivity were determined. Interferences due to cations and anions were investigated and various masking agents for alleviating their inhibition were studied. The method has been found very useful in determining ratios of Cu(I) to Cu(II) in bacterial leach liquors and should play a significant role in determining the reaction mechanisms of biological leaching and for environmental monitoring.     

Hydropathic analysis of the free energy differences in anthracycline antibiotic binding to DNA

Molecular models of six anthracycline antibiotics and their complexes with 32 distinct DNA octamer sequences were created and analyzed using HINT (Hydropathic INTeractions) to describe binding. The averaged binding scores were then used to calculate the free energies of binding for comparison with experimentally determined values. In parsing our results based on specific functional groups of doxorubicin, our calculations predict a free energy contribution of –3.6 ± 1.1 kcal mol^–1 (experimental –2.5 ± 0.5 kcal mol^–1) from the groove binding daunosamine sugar. The net energetic contribution of removing the hydroxyl at position C9 is –0.7 ± 0.7 kcal mol^–1 (–1.1 ± 0.5 kcal mol^–1). The energetic contribution of the 3′ amino group in the daunosamine sugar (when replaced with a hydroxyl group) is –3.7 ± 1.1 kcal mol^–1 (–0.7 ± 0.5 kcal mol^–1). We propose that this large discrepancy may be due to uncertainty in the exact protonation state of the amine. The energetic contribution of the hydroxyl group at C14 is +0.4 ± 0.6 kcal mol^–1 (–0.9 ± 0.5 kcal mol^–1), largely due to unfavorable hydrophobic interactions between the hydroxyl oxygen and the methylene groups of the phosphate backbone of the DNA. Also, there appears to be considerable conformational uncertainty in this region. This computational procedure calibrates our methodology for future analyses where experimental data are unavailable.     

Influence of soil temperature on methane emission from rice paddy fields

Methane emission rates from an Italian rice paddy field showed diel and seasonal variations. The seasonal variations were not closely related to soil temperatures. However, the dieL changes of CH₄ fluxes were significantly correlated with the diel changes of the temperature in a particular soil depth. The soil depths with the best correlations between CH4 flux and temperature were shallow (1–5cm) in May and June, deep (10–15cm) in June and July, and again shallow (1–5 cm) in August. Apparent activation energies (E_a) calculated from these correlations using the Arrhenius model were relatively low (50–150 kJ mol^–1) in May and June, but increased to higher values (80–450 kJ mol^–1) in August. In the laboratory, CH₄ emission from two rice cultures incubated at temperatures between 20 and 38°C showed E . values of 41 and 53 kJ mol^–1) Methane production in anoxic paddy soil suspensions incubated between 7 and 43°C showed E values between 53 and 132 kJ mol^–1 with an average value of 85 kJ mol^–1) and in pure cultures of hydrogenotrophic methanogenic bacteria E _a values between 77 and 173 (average 126) kJ mol^–1. It is suggested that diel changes of soil properties other than temperature affect CH₄ emission rates, e.g. diel changes in root exudation or in efficiency of CH⁴ oxidation in the rhizosphere.     

Energy-rich glyceric acid oxygen esters: Implications for the origin of glycolysis

The apparent Gibbs free energy change of hydrolysis (G°', pH 7) of the 2- and 3-O-glyceroyl esters of 2- and 3-O-L-glyceroyl-L-glyceric acid methyl ester were measured at 25 °C. The 2- and 3-glyceroyl esters were found to be energy-rich with G°' values of –9.1 kcal mol^–1 and –7.8 kcal mol, respectively. This result indicates that the analogous 2- and 3-glyceroyl esters of polyglyceric acid are also energy-rich and, therefore, could have acted as an energy source for primitive phosphoanhydride synthesis.     

Metal-humic complexes and plant micronutrient uptake: a study based on different plant species cultivated in diverse soil types

There are several studies in the literature dealing with the effect of metal-humic complexes on plant metal uptake, but none of them correlate the physicochemical properties of the complexes with agronomic results. Our study covers both aspects under various experimental conditions. A humic extract (SHE) obtained from a sapric peat was selected for preparing the metal–humic complexes used in plant experiments. Fe–, Zn– and Cu–humic complexes with a reaction stoichiometry of 2:0.25 (humic:metal, w/w) were chosen after studying their stability and solubility with respect to pH (6–9) and the humic:metal reaction stoichiometry. Wheat and alfalfa plants were greenhouse cultured in pots containing one of three model soils: an acid, sandy soil and two alkaline, calcareous soils. Treatments were: control (no additions), SHE (53 mg kg^–1 of SHE), and metal (Cu, Zn and Fe)–SHE complexes (2.5 and 5 mg kg^–1 of metal rate and a SHE concentration to make 53 mg kg ^–1). Cu- and Zn–humic complexes significantly (p0.05) increased the plant uptake and the DTPA-extractable soil fraction of complexed micronutrients in most plant–soil systems. However, these effects were associated with significant increases (p0.05) of shoot and root dry weight only in alfalfa plants. In wheat, significant increases of root and shoot dry matter were only observed in the Cu–humic treated plants growing in the acid soil, where Cu deficiency was more intense. The Fe–humic complex did not increase Fe plant assimilation in any plant–soil system, but SHE increased Fe-uptake and/or DTPA-extractable soil Fe in the wheat–calcareous soil systems. These results, taken together with those obtained from the study of the pH- and SHE:metal ratio-dependent SHE complex solubility and stability, highlight the importance of the humic:Fe complex stoichiometry on iron bioavailability as a result of its influence on complex solubility.     

Selection of a support for immobilization of a microbial lipase for the hydrolysis of triglycerides

Baterial lipase from Staphylococcus carnosus (pLipMut2) has been immobilized on various supports in order to determine a suitable immobilization technique in terms of activity and stability, when utilized for the hydrolysis of tributyrin. The hydrophobic materials PBA Eupergit and PBA Eupergit 250L prooved to be appropriate supports, when the enzyme was crosslinked with glutaraldehyde after adsorption. No desorption of the immobilized enzyme occured during operation. The pore size of the support has a strong effect on the activity but does not influence stability.The initial activity for immobilized and soluble lipase is found to follow the Arrhenius equation at low temperature, where mass transfer does not affect reaction kinetics. Activation energies for soluble and immobilized lipase were evaluated to be 21.7 kJ mol^–1 and 60.8 kJ mol^–1, respectively.Operational stability was studied in a packed bed recirculation reactor. Thermal desactivation followed first order kinetics with a half-life of 1340 h at 10°C. Model calculations for productivity showed, that optimal temperatures for high productivity are well below the temperature of maximal activity.List of Symbols E _a [kJ mol^–1] activation energy - E _d [kJ mol^–1] activation energy of desactivation - H [–] half-number - k _d [h^–1] desactivation constant - k _d, [h^–1] constant - k _N [–] desactivation constant (number) - N [–] number of runs - p [mol dm^–3] productivity - t [h] time - t _0.5 [h] half-life - T [K] absolute temperature - V [U ml^–1] activity - V(N) [Uml^–1] activity exhibited in the n-th run - V _s,O [U ml^–1] initial activity of supernatant - V _s, [U ml^–1] activity of supernatant after immobilization - V _O [U ml^–1] initial activity - V [U ml^–1] constant - _imm [–] activity yield - [ml ml^–1] ratio of volume of support to volume of supernatant Financial support of this work by the Deutsche Forschungsgemeinschaft (SFB 145, A15) is gratefully acknowledged.     

Conformational changes in human red cell membrane proteins induced by sugar binding

Summary We have previously shown that the human red cell glucose transport protein and the anion exchange protein, band 3, are in close enough contact that information can be transmitted from the glucose transport protein to band 3. The present experiments were designed to show whether information could be transferred in the reverse direction, using changes in tryptophan fluorescence to report on the conformation of the glucose transport protein. To see whether tryptophan fluorescence changes could be attributed to the glucose transport protein, we based our experiments on procedures used by Helgerson and Carruthers [Helgerson, A.L., Carruthers, A., (1987)J. Biol. Chem. 262:5464–5475] to displace cytochalasin B (CB), the specificd-glucose transport inhibitor, from its binding site on the inside face of the glucose transport protein, and we showed that these procedures modified tryptophan fluorescence. Addition of 75mm maltose, a nontransportable disaccharide which also displaces CB, caused a timedependent biphasic enhancement of tryptophan fluorescence in fresh red cells, which was modulated by the specific anion exchange inhibitor, DBDS (4,4-dibenzamido-2,2-stilbene disulfonate). In a study of nine additional disaccharides, we found that both biphasic kinetics and DBDS effects depended upon specific disaccharide conformation, indicating that these two effects could be attributed to a site sensitive to sugar conformation. Long term (800 sec) experiments revealed that maltose binding (±DBDS) caused a sustained damped anharmonic oscillation extending over the entire 800 sec observation period. Mathematical analysis of the temperature dependence of these oscillations showed that 2 m DBDS increased the damping term activation energy, 9.5±2.8 kcal mol^–1 deg^–1, by a factor of four to 39.7±5.1 kcal mol^–1 deg^–1, providing strong support for the view that signalling between the glucose transport protein and band 3 goes in both directions.     

Is Ag(I) an adequate probe for Cu(I) in structural copper–metallothionein studies?

The binding abilities of silver(I) to mammalian MT 1 have been studied and compared with those of copper(I), recently reported [Bofill et al. (2001) J Biol Inorg Chem 6:408–417], with the aim of analyzing the suitability of Ag(I) as a Cu(I) probe in Cu–MT studies. The Zn/Ag replacement in recombinant mouse Zn₇–MT 1 and corresponding Zn₄-MT 1 and Zn₃-MT 1 fragments, as well as the stepwise incorporation of Ag(I) to the corresponding apo-MTs, have been followed in parallel by various spectroscopic techniques including electronic absorption (UV–vis), circular dichroism (CD) and electrospray mass spectrometry coupled to capillary zone electrophoresis (CZE-ESI-MS). A comparative analysis of the sets of data obtained in the titration of Zn₇–MT 1, Zn₄–MT 1 and Zn₃-MT 1 with AgClO₄ at pH 7.5 and 2.5 has led to the reaction pathways followed during the incorporation of silver to these proteins under these specific conditions, disclosing unprecedented stoichiometries and structural features for the species formed. Thus, the Zn/Ag replacement in Zn₇–MT 1 at pH 7.5 has revealed the subsequent formation of Ag₄Zn₅–MT, Ag₇Zn₃–MT, Ag₈Zn₃–MT, Ag₁₀Zn₂–MT, Ag₁₂Zn₁–MT, Ag_x–MT, x=14–19, whose structure consists of two additive domains only if Zn(II) remains coordinated to the protein. A second structural role for Zn(II) has been deduced from the different folding found for the Ag_x–MT species of the same stoichiometry formed at pH 7.5 or 2.5. Comparison of the binding features of Cu(I) and Ag(I) to the entire MT at pH 7.5 shows that, among all the _xZn_y–MT (0y<7) species found, only M^I₄Zn₅–MT [(Zn₄)(₄Zn₁)] and M^I₇Zn₃–MT [(₃Zn₂)(₄Zn₁)], which form during the first stages of the Zn(II)/M(I) metal replacement, show comparable 3D structures; thus, they are the only species where Ag(I) ions can be predicted to be an adequate probe for Cu(I).Electronic Supplementary Material Supplementary material is available in the online version of this article at .     

Thermal stability and thermodynamic analysis of native and methoxypolyethylene glycol modified trypsin

Four methoxypolyethylene glycols (MPEG, molecular masses 350, 750, 2000 and 5000 Da), each activated by nitrophenyl chloroformate, were used to modify trypsin. Compared with the native trypsin, the MPEG-modified trypsin was more stable against temperature between 30°C and 70°C, longer chain of MPEG moiety corresponding to higher thermal stability. The T for the native and the modified trypsin (0.4 mg ml^–1) was increased from 47°C to 66°C. The stabilization effect caused by MPEG modification was the result of decreasing in both the autolysis rate and the thermal denaturation rate. The thermodynamic analysis of the thermal denaturation process showed that the activation free energy (G^*) of the native and the modified trypsin at 60°C was increased from 102.9 to 109.3 kJ mol^–1; the activation enthalpy (H^*) was increased from 57.4 to 86.9 kJ mol^–1; the activation entropy (S^*) was increased from –136 to –67 J molK^–1. A possible explanation for the decreased thermal denaturation rate caused by MPEG modification was also discussed.     

The reactions between glutaraldehyde and various proteins. An investigation of their kinetics

Synopsis Glutaraldehyde reacts readily with various proteins in solution. With high concentrations of both, the solutions become yellow and many proteins form a gel. At low concentrations the reactions may be followed by the changes in the u.v. spectrum between 250 and 300 nm. The reverse reaction does not proceed to any detectable extent. The kinetics are pseudo-first-order. The activation energies for the reactions between proteins and glutaraldehyde were found to be about II kcal/mole. This suggests that the proteins have not been denatured to any marked extent by the glutaraldehyde fixation. The rates of reactions increase with pH. The rate of formation of glutaraldehyde-protein links per protein molecule glutarated is approximately I sec^–1 mol^–1 1.     

Bacterial production in a mesohumic lake estimated from [14C]leucine incorporation rate

Incorporation of [¹⁴C]leucine into proteins of bacteria was studied in a temperate mesohumic lake. The maximum incorporation of [¹⁴C] leucine was reached at a concentration of 30 nm determined in dilution cultures. Growth experiments were used to estimate factors for converting leucine incorporation to bacterial cell numbers or biomass. The initially high conversion factors calculated by the derivative method decreased to lower values after the bacteria started to grow. Average conversion factors were 7.09 × 10¹⁶ cells mol^–1 and 7.71 × 10¹⁵ m³ mol^–1, if the high initial values were excluded. Using the cumulative method, the average conversion factor was 5.38 × 10¹⁵ m^–3 mol^–1 I . The empirically measured factor converting bacterial biomass to carbon was 0.36 pg C m^–3 or 33.1 fg C cell^–1. Bacterial production was highest during the growing season, ranging between 1.8 and 13.2 g C liter^–1 day^–1, and lowest in winter, at 0.2–2.9 g C liter^–1 day^–1. Bacterial production showed clear response to changes in the phytoplankton production, which indicates that photosynthetically produced dissolved compounds were used by bacteria. In the epilimnion bacterial production was, on average, 19–33% of primary production. Assuming 50% growth efficiency for bacteria, the allochthonous organic carbon could have also been an additional energy and carbon source for bacteria, especially in autumn and winter. In winter, a strong relationship was found between temperature and bacterial production. The measuring of [¹⁴C]leucine incorporation proved to be a simple and useful method for estimating bacterial production in humic water. However, an appropriate amount of [¹⁴C]leucine has to be used to ensure the maximum uptake of label and to minimize isotope dilution.     

Probing the nature of hydrogen bonds in DNA base pairs

Energy decomposition analyses based on the block-localized wave-function (BLW-ED) method are conducted to explore the nature of the hydrogen bonds in DNA base pairs in terms of deformation, Heitler–London, polarization, electron-transfer and dispersion-energy terms, where the Heitler–London energy term is composed of electrostatic and Pauli-exchange interactions. A modest electron-transfer effect is found in the Watson–Crick adenine–thymine (AT), guanine–cytosine (GC) and Hoogsteen adenine-thymine (H-AT) pairs, confirming the weak covalence in the hydrogen bonds. The electrostatic attraction and polarization effects account for most of the binding energies, particularly in the GC pair. Both theoretical and experimental data show that the GC pair has a binding energy (−25.4 kcal mol⁻¹ at the MP2/6-31G** level) twice that of the AT (−12.4 kcal mol⁻¹) and H-AT (−12.8 kcal mol⁻¹) pairs, compared with three conventional N-H···O(N) hydrogen bonds in the GC pair and two in the AT or H-AT pair. Although the remarkably strong binding between the guanine and cytosine bases benefits from the opposite orientations of the dipole moments in these two bases assisted by the π-electron delocalization from the amine groups to the carbonyl groups, model calculations demonstrate that π-resonance has very limited influence on the covalence of the hydrogen bonds. Thus, the often adopted terminology “resonance-assisted hydrogen bonding (RHAB)” may be replaced with “resonance-assisted binding” which highlights the electrostatic rather than electron-transfer nature of the enhanced stabilization, as hydrogen bonds are usually regarded as weak covalent bonds. Figure Electron density difference (EDD) maps for the GC pair: a shows the polarization effect (isodensity 1.2×10⁻³ a.u.); b shows the charge transfer effect (isodensity 2×10⁻⁴ a.u.) Dedicated to Professor Paul von Ragué Schleyer on the occasion of his 75th birthday     

Zwitterionic conformers of pyrrolysine and their interactions with metal ions—a theoretical study

A total of 16 pyrrolysine conformers in their zwitterionic forms are studied in gas and simulated aqueous phase using a polarizable continuum model (PCM). These conformers are selected on the basis of our study on the intrinsic conformational properties of non-ionic pyrrolysine molecule in gas phase [Das and Mandal (2013) J Mol Model 19:1695?1704]. In aqueous phase, the stable zwitterionic pyrrolysine conformers are characterized by full geometry optimization and vibrational frequency calculations using B3LYP/6-311++G(d,p) level of theory. Single point calculations are also carried out at MP2/6-311++G(d,p) level. Characteristic intramolecular hydrogen bonds present in each conformer, their relative energies, theoretically predicted vibrational spectra, rotational constants and dipole moments are systematically reported. The calculated relative energy range of the conformers at B3LYP/6-311++G(d,p) level is 5.19 kcal mol^?1 whereas the same obtained by single point calculations at MP2/6-311++G(d,p) level is 4.58 kcal mol^?1. A thorough analysis reveals that four types of intramolecular H-bonds are present in the conformers; all of which play key roles in determining the energetics and in imparting the observed conformations to the conformers. The vibrational frequencies are found to shift invariably toward the lower side of frequency scale corresponding to the presence of the H-bonds. This study also points out that conformers with diverse structural motifs may differ in their thermodynamical stability by a narrow range of relative energy. The effects of metal coordination on the relative stability order and structural features of the conformers are examined by complexing five zwitterionic conformers of pyrrolysine with Cu⁺² through their carboxylate groups. The interaction enthalpies and Gibbs energies, rotational constants, vibrational frequencies and dipole moments of the metal complexes calculated at B3LYP level are also reported. The zwitterionic conformers of pyrrolysine are not stable in gas phase; after geometry optimization they are converted to the non-ionic forms.