Calculated Binding Enthalpies Research Articles

How strongly do Janus all-cis C6H6F6 and C6H6Cl6 bind ions in the gas-phase?

The high-level G4(MP2) composite method and B2-PLYP double-hybrid density functional theory have been used to investigate interactions of all-cis hexafluorocyclohexane and hexachlorocyclohexane molecules with a series of anions and cations in the gas phase. The calculated binding enthalpies are exceptionally high for bound complexes formed between these ions and molecular species. The binding energies of Cl− to all-cis hexafluorocyclohexane and all-cis hexachlorocyclohexane obtained at the G4(MP2)[B2-PLYP] theoretical level are 159.3 [159.6] and 149.3 [147.7] kJ mol−1, respectively. Similar observations are made for some of the other considered complexes. We also show that for anionic complexes, the strongest complexes are formed with all-cis hexachlorocyclohexane rather than with all-cis hexafluorocyclohexane. However, for cationic complexes, an opposite behaviour is observed, with the exception of some cations such as Mg2+ and Zn2+.

Structural Investigation of the Dopamine-2 Receptor Agonist Bromocriptine Binding to Dimeric D2HighR and D2LowR States.

The active (D2HighR) and inactive (D2LowR) states of dimeric dopamine D2 receptor (D2R) models were investigated to clarify the binding mechanisms of the dopamine agonist bromocriptine, using Molecular Dynamics (MD) simulation. The aim of this comprehensive study was to investigate the critical effects of bromocriptine binding on each distinct receptor conformation. The different binding modes of the bromocriptine ligand in the active and inactive states have a significant effect on the conformational changes of the receptor. Based on the MM/GBSA approach, the calculated binding enthalpies of bromocriptine demonstrated selectivity toward the D2HighR active state. There is good agreement between the calculated and experimentally measured D2HighR selectivity. In the ligand-binding site, the key amino acids identified for D2HighR were Asp114(3.32) and Glu95(2.65), and for D2LowR, it was Ser193(5.42). Moreover, analysis of replicate MD trajectories demonstrated that the bromocriptine structure was more rigid at the D2HighR state and more flexible at the D2LowR state. However, the side chains of the ligand-receptor complex of D2HighR showed larger variations relative to the corresponding regions of D2LowR. The present study is part of an ongoing research program to study D2R conformational changes during ligand activation and to evaluate the conformational state selectivity for ligand binding.

Epidemiological link between multiple chemical sensitivity/idiopathic environmental intolerance and birth by caesarean section

Isothermal titration calorimetry (ITC) was used to characterize the thermodynamics of the complexation processes of α-, β- and γ-cyclodextrin (CD) with ferulate (FER) in aqueous solutions. The equilibrium constants of ferulate complexation with CDs (Kc, in dm3 mol−1) at pH 9.0 and 25.0 °C were: 176.5 ± 5.0 (β-CD), 53.2 ± 3.4 (α-CD) and 19.4 ± 0.4 (γ-CD). Although FER–β-CD is the tightest complex of the three studied, its binding reaction is also the least exothermic and the only one that is entropically favored. Calculated binding enthalpies, based on the buried surface area upon complexation, are close to those determined by ITC except for the FER–β-CD complex which is more than two times more exothermic. According to these results and those obtained by molecular docking simulations, it is proposed that ferulate binds to the hydrophobic cavity of β-CD, displacing more water molecules than in the other two CD complexes.

Binding Sites, Geometry, and Energetics of Propene at Nanoparticulate Au/TiO2

Surface adsorption and activation of propene, to catalytically produce propene oxide, is the first step in the industrially important gas-phase epoxidation reaction. Motivated by the significant practical importance of this reaction, site-specific adsorption of propene on nanoparticulate titania-supported Au (Au/TiO2) has been systematically characterized through Fourier transform infrared (FTIR) spectroscopy and density functional theoretical (DFT) calculations. The infrared spectra, recorded during propene uptake at low surface temperatures, and DFT calculations identified two distinct propene–surface binding motifs. Propene was found to bind to the surface through a π-interaction at TiO2 sites remote from the Au particles and through a (πσ)-interaction at a single atomic Au site, distinguishable through the stretching frequency of the propene double bond. Temperature-programmed desorption and calculated binding enthalpies for the minimum-energy configurations revealed the propene–Au interaction to have...

Thermodynamic analysis of ferulate complexation with α-, β- and γ-cyclodextrins

Isothermal titration calorimetry (ITC) was used to characterize the thermodynamics of the complexation processes of α-, β- and γ-cyclodextrin (CD) with ferulate (FER) in aqueous solutions. The equilibrium constants of ferulate complexation with CDs (Kc, in dm3mol−1) at pH 9.0 and 25.0°C were: 176.5±5.0 (β-CD), 53.2±3.4 (α-CD) and 19.4±0.4 (γ-CD). Although FER–β-CD is the tightest complex of the three studied, its binding reaction is also the least exothermic and the only one that is entropically favored. Calculated binding enthalpies, based on the buried surface area upon complexation, are close to those determined by ITC except for the FER–β-CD complex which is more than two times more exothermic. According to these results and those obtained by molecular docking simulations, it is proposed that ferulate binds to the hydrophobic cavity of β-CD, displacing more water molecules than in the other two CD complexes.

Surface Binding of Organophosphates on Silica: Comparing Experiment and Theory

A consistent embedding hierarchy is applied to the calculation of binding enthalpies for organophosphate molecules to a silica surface and compared to experiment. The interaction of four probe molecules, dimethyl methylphosphonate (DMMP), diisopropyl methylphosphonate (DIMP), diisopropyl fluorophosphate (DFP), and sarin, with the silica surface is examined. Quantum chemical methods are employed to compute binding enthalpies and vibrational spectra for all interactions between probe molecules and silanol sites on the silica surface. Comparison with experimentally measured infrared shifts indicates that the theoretically modeled adsorption sites are similar to those found in experiment. The calculated binding enthalpies agree well with experiment for sarin, ΔHads,443K = −22.0 kcal/mol (calculated) vs −18.8 ± 5.5 kcal/mol (measured, 433 K < Texpt < 453 K), and DIMP, ΔHads,463K = −26.9 kcal/mol (calculated) vs −29.3 ± 0.9 kcal/mol (measured, 453 K < Texpt < 473 K). Agreement with experiment is less good for D...

Threshold Collision‐Induced Dissociation of Hydrated Magnesium: Experimental and Theoretical Investigation of the Binding Energies for Mg2+(H2O)x Complexes (x=2–10)

The sequential bond energies of Mg(2+)(H2O)x complexes, in which x=2-10, are measured by threshold collision-induced dissociation in a guided ion beam tandem mass spectrometer. From an electrospray ionization source that produces an initial distribution of Mg(2+)(H2O)x complexes in which x=7-10, complexes down to x=3 are formed by using an in-source fragmentation technique. Complexes smaller than Mg(2+)(H2O)3 cannot be formed in this source because charge separation into MgOH(+)(H2O) and H3O(+) is a lower-energy pathway than simple water loss from Mg(2+)(H2O)3. The kinetic energy dependent cross sections for dissociation of Mg(2+)(H2O)x complexes, in which x=3-10, are examined over a wide energy range to monitor all dissociation products and are modeled to obtain 0 and 298 K binding energies. Analysis of both primary and secondary water molecule losses from each sized complex provides thermochemistry for the sequential hydration energies of Mg(2+) for x=2-10 and the first experimental values for x=2-4. Additionally, the thermodynamic onsets leading to the charge-separation products from Mg(2+)(H2O)3 and Mg(2+)(H2O)4 are determined for the first time. Our experimental results for x=3-7 agree well with quantum chemical calculations performed here and previously calculated binding enthalpies, as well as previous measurements for x=6. The present values for x=7-10 are slightly lower than previous experimental results and theory, but within experimental uncertainties.

Density Functional Study of Hydrogen Bond Formation between Methanol and Organic Molecules Containing Cl, F, NH2, OH, and COOH Functional Groups

Various hydrogen-bonded complexes of methanol with different proton accepting and proton donating molecules containing Cl, F, NH(2), OH, OR, and COOH functional groups have been modeled using DFT with hybrid B3LYP and M05-2X functionals. The latter functional was found to provide more accurate estimates of the structural and thermodynamic parameters of the complexes of halides, amines, and alcohols. The characteristics of these complexes are influenced not only by the principle hydrogen bond of the methanol OH with the proton acceptor heteroatom, but also by additional hydrogen bonds of a C-H moiety with methanol oxygen as a proton acceptor. The contribution of the former hydrogen bond in the total binding enthalpy increases in the order chlorides < fluorides < alcohols < amines, while the contribution of the second type of hydrogen bond increases in the reverse order. A general correlation was found between the binding enthalpy of the complex and the electrostatic potential at the hydrogen center participating in the formation of the hydrogen bond. The calculated binding enthalpies of different complexes were used to clarify which functional groups can potentially form a hydrogen bond to the 2'-OH hydroxyl group in ribose, which is strong enough to block it from participation in the intramolecular catalytic activation of the peptide bond synthesis. Such blocking could result in inhibition of the protein biosynthesis in the living cell if the corresponding group is delivered as a part of a drug molecule in the vicinity of the active site in the ribosome. According to our results, such activity can be accomplished by secondary or tertiary amines, alkoxy groups, deprotonated carboxyl groups, and aliphatic fluorides, but not by the other modeled functional groups.

Mixed implicit/explicit solvation models in quantum mechanical calculations of binding enthalpy for protein–ligand complexes

AbstractAn approach to quantum mechanical investigation of interactions in protein–ligand complexes has been developed that treats the solvation effect in a mixed scheme combining implicit and explicit solvent models. In this approach, the first solvation shell of the solvent around the solute is modeled with a limited number of hydrogen bonded explicit solvent molecules. The influence of the remaining bulk solvent is treated as a surrounding continuum in the conductor‐like screening model (COSMO). The enthalpy term of the binding free energy for the protein–ligand complexes was calculated using the semiempirical PM3 method implemented in the MOPAC package, applied to a trimmed model of the protein–ligand complex constructed with special rules. The dependence of the accuracy of binding enthalpy calculations on size of the trimmed model and number of optimized parameters was evaluated. Testing of the approach was performed for 12 complexes of different ligands with trypsin, thrombin, and ribonuclease with experimentally known binding enthalpies. The root‐mean‐square deviation (RMSD) of the calculated binding enthalpies from experimental data was found as ∼1 kcal/mol over a large range. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

The Effect of Alkylation of N- and O-Donor Atoms on Their Strength of Coordination to Silver(I)

The observation that alkylation of amine ligands can lead to enhanced coordination to silver(I) is investigated through the determination of structures and incremental binding enthalpies for Ag+(L)n ionic clusters (with L = NH3, NH2Me, NHMe2, NMe3, H2O, MeOH, and Me2O for n = 1−2), using density-functional and CCSD(T) electronic structure methods. For the nonalkylated complexes Ag+(H2O), Ag+(NH3), Ag+(H2O)2, and Ag+(NH3)2, the calculated binding enthalpies agreed well with experimental values for all but Ag+(NH3)2, while good agreement between the binding entropies was achieved for all but Ag+(H2O). As a function of the degree of alkylation, the calculated binding enthalpies initially increase but then decrease. The results are interpreted in terms of the bonding models of Meyerstein and of Deng et al. as arising from increased ligand σ-donating ability and reduced ion-ligand electrostatic interactions. It is clear that gas-phase effects are insufficient to explain the sometimes observed increased binding energies of tertiary macrocyclic amines compared to secondary ones.

Reactions of multidentate ligands with ligated alkali cation complexes: self-exchange and “sandwich” complex formation kinetics of gas phase crown ether–alkali cation complexes

Natural abundance isotopic labeling has been employed to study the reactions of labeled LM + complexes with L (L = triglyme, TG; 12-crown-4, C4; 15-crown-5, C5; 18-crown-6, C6; or 21-crown-7, C7; M = Li, Na, K, Rb, or Cs) in the gas phase using Fourier transform ion cyclotron resonance mass spectrometry. Reaction efficiencies for both ligand exchange and the formation of 2:1 ligand:metal “sandwich” complexes were determined. For a given ligand, self-exchange rates generally decrease with increasing metal size, while the sandwich complex formation rates show strong dependence on the relative sizes of the metal ions and ligand cavities. Acyclic TG complexes undergo self-exchange more rapidly than the analogous cyclic C4 complexes, whereas the sandwich complex formation rates are faster for the C4 complexes. Sandwich formation rates show a weak positive pressure dependence, as increased pressure leads to increased collisional stabilization of the complexes. Extrapolation of the rates to the zero pressure limits still yields significant rates, reflecting radiative stabilization. The self-exchange reactions have weak, negative pressure dependences, suggesting they are in direct competition with sandwich complex formation. Analysis of the sandwich complex formation radiative association kinetics yields estimates of binding enthalpies for attachment of the second ligand. Trends in the binding enthalpies, like the kinetics, show strong dependence on the relative sizes of the metal ions and ligand cavities. For a given metal, binding of a second TG is weaker than binding of a second C4. Binding enthalpies for the second ligand are in every case substantially less than calculated binding enthalpies for the first ligand to attach to a given metal.

A Study of Silver (I) Ion−Organonitrile Complexes: Ion Structures, Binding Energies, and Substituent Effects

Density functional calculations at B3LYP/DZVP are used to obtain the binding enthalpies and free energies for the reaction Ag+ + XCN → AgNCX+, where X = H, CH3, NH2, OH, F, CF3, CN, NO2, N(CH3)2, C6H5, p-C6H4N(CH3)2, p-C6H4NO2, and p-C6H4NH2. The calculated binding enthalpies at 298 K range from 52.2 kcal mol-1 for X = p-C6H4N(CH3)2 to 21.3 kcal mol-1 for X = NO2. Calculations at this level of theory are also used to optimize the structures of Ag(NCCH3)n+ and Ag(NCH)n+ ions, where n = 1−6. The binding enthalpies for the addition of the first and second molecules of CH3CN are 40.1 and 35.3 kcal mol-1, whereas for HCN, they are calculated to be 31.2 and 28.3 kcal mol-1, respectively. The binding enthalpies of the third and fourth ligands are much smaller at 15.9 and 10.8 kcal mol-1 for CH3CN and 13.5 and 9.7 kcal mol-1 for HCN. The 5- and 6-coordinate structures have positive free energies of formation with both ligands. Electrospraying a solution of AgNO3 and acetonitrile in water shows the dominant ions t...

Electronic and Vibrational Circular Dichroism of Model β-Lactams: 3-Methyl- and 4-Methylazetidin-2-one

The chiroptical properties of the simplest chiral β-lactams, 3- and 4-methylazetidin-2-one, 1 and 2, respectively, were investigated. The experimental vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra were measured and compared with ab initio predictions. Both compounds were found to form dimers with calculated binding enthalpies and free energies of about −51 kJ/mol and −6 to −8 kJ/mol, respectively. The experimentally measured IR and VCD spectra were measured in concentrated nonpolar (CCl4) solution and are in agreement with the predicted IR and VCD spectra of the dimeric forms, 12 and 22, but not the monomers. The most intense dimer VCD bands originate from in-plane N-H wags, which perturb the H-bonded cyclic array. At the more dilute concentrations employed for the ECD spectra, the experimental ECD spectra in heptane were interpreted satisfactorily as arising from a mixture consisting predominantly of monomers. In protic solvent (H2O, MeOH), the ECD spectra are consistent with H-bonded monomers. Simple modeling suggests that the rotational strengths of the first electronic transition gain most of their intensity from the nonplanarity of the amide chromophore, the contributions of which follow a spiral rule previously enunciated.