Thermodynamic study on inclusion complex formation of riboflavin with hydroxypropyl-β-cyclodextrin in water

The inclusion complex formation of riboflavin (RF) with hydroxypropyl-β-cyclodextrin (HP-β-CD) in water was investigated by ¹H NMR, UV-vis spectroscopy, and solubility methods. A 1:1 stoichiometry and thermodynamic parameters of complex formation (K, Δ_c G ⁰, Δ_c H ⁰, and Δ_c S ⁰) were determined. Complexation was characterized by negative enthalpy and entropy changes due to prevalence of van der Waals interactions and hydrogen bonding between polar groups of the solutes. A partial insertion of RF into macrocyclic cavity was revealed on the basis of ¹H NMR data and molecular mechanics calculation. Location of benzene ring of RF molecule inside the hydrophobic cavity of HP-β-CD results in an increase of aqueous solubility of the former.     

Molecular Modeling for Mobile Phase Optimization in RP-HPLC

Abstract

The applicability of molecular parameters calculated on the bases of molecular mechanics have been investigated for the prediction of reversed-phase retention behavior of structurally unrelated series of drug molecules. Non-polar, non-polar unsaturated and polar surface areas, surface energies, dipole moments, van der Waals radii and hydrophobicity values expressed by the logarithm of the octanol/water partition coefficients have been calculated from the molecular structure. The reversed-phase retention behavior was described by the slope and the intercept of the straight lines obtained by plotting the log k¹ values against the acetonitrile concentration of the mobile phase. The acetonitrile concentration (OP%₀) which was needed for the log k¹ = 0 retention was also calculated from the slope and intercept values. Step-wise linear regression analyses have been applied for revealing the correlations between the investigated parameters. The slope values could be described by the difference of the non-polar and non-polar accessible surface areas or by the total surface energy values and the van der Waals radii. The intercept values could be described by the hydrophobicity parameter, the slope and the reciprocal values of dipole moment. The acetonitrile concentration for the log k'=O retention (OP%₀) could have been calculated from the hydrophobicity and the non-polar unsaturated surface area values of the investigated compounds.     

Van der Waals radii of elements from the data of structural inorganic chemistry

Van der Waals radii of elements were determined from the data of the structural inorganic chemistry: from intersitial distances in CdX₂- and graphite-type structures, bond lengths in van der Waals molecules, molar volumes of A₂-type substances, refractometry data, and from quantum chemical and correlation ratios. The recommended values of van der Waals radii of elements are tabulated.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 24–29, January, 1995.The author is grateful to the administration of the Department of Chemistry at the University of Durham (Great Britain) for the opportunity to perform this work and to Prof. J. Howard and Prof. K. Wade for useful discussions.     

Accurate DMBE Potential Energy Surface For the N(2D) + H2(1Σ g + ) Reaction Using an Improved Switching Function Formalism

A single-sheeted double many-body expansion (DMBE) potential energy surface is reported for the 1 ² A′′ state of NH₂. To approximate its true multi-sheeted nature, a novel switching function that imposes the correct behavior at the H₂(X ¹Σ _g ⁺)+ N(² D) and NH(X ³Σ^-) + H(² S) dissociation limits has been suggested. The new DMBE form is shown to fit with high accuracy an extensive set of new ab initio points (calculated at the multi-reference configuration interaction level using the full valence complete active space as reference and aug-cc-pVQZ and aug-cc-pV5Z basis sets) that have been semiempirically corrected at the valence regions by scaling the n-body dynamical correlation terms such as to account for the finite basis set size and truncated configuration interaction expansion. A detailed study of the N(² D) ... H₂(X ¹Σ _g ⁺) van der Waals region has also been carried out. These calculations predict a nearly free rigid-rotor with two shallow van der Waals wells of C _2v and C _{∞ v} symmetries. Such a result contrasts with previous cc-pVTZ calculations which predict a single T-shaped van der Waals structure. Except in the vicinity of the crossing seam, which is replaced by an avoided intersection, the fit shows the correct physical behavior over the entire configurational space. The topographical features of the new DMBE potential energy surface are examined in detail and compared with those of other potential functions available in the literature. Amongst such features, we highlight the barrier for linearization (11,802 cm^-1) which is found to overestimate the most recent empirical spectroscopic estimate by only 28 cm^-1. Additionally, the T-shaped N(² D) ... H₂ van der Waals minimum is predicted to have a well depth of 90 cm^-1, being 11 cm^-1 deeper than the C _{∞ v} minimum. The title DMBE form is therefore recommendable for dynamics studies of both non-reactive and reactive N(² D)+H₂ collisions.     

COSMIC(90): An improved molecular mechanics treatment of hydrocarbons and conjugated systems

Summary Four modifications to the COSMIC molecular mechanics force field are described, which greatly increase both its versatility and the accuracy of calculated conformational energies. The Hill non-bonded van der Waals potential function has been replaced by a two-parameter Morse curve and a new H-H potential, similar to that in MM3, incorporated. Hydrocarbon energies in particular are much improved.A simple iterative Hückel pi-electron molecular orbital calculation allows modelling of conjugated systems. Calculated bond lengths and rotational barriers for a series of conjugated hydrocarbons and nitrogen heterocycles are shown to be as accurate as those determined by the MM2 SCF method.Explicit hydrogen-bonding potentials for H-bond acceptor-donor atom pairs have been included to give better hydrogen bond energies and lengths. The van der Waals radii of protonic hydrogens are reduced to 0.5 Å and the energy well depth is increased to 1.0 kcal mol^-1.Two new general atom types, N⁺ _sp ² and O^- _sp ³ , have been introduced which allow a wide variety of charged conjugated systems to be studied. A minimum of parameterisation is required, as the new types are easily included in the Hückel scheme which automatically adjusts bond and torsional parameters according to the defined bond-order relationships.     

Van der Waals volume fragmental constants

Van der Waals (vdW) volumes (V_w,x) of 117 molecular fragments (X) have been calculated by numerical integration of the van der Waals envelope using the hard-sphere approximation, standard geometries, and effective atomic van der Waals radii which were determined by comparison of their effects on the predicted sterically allowed conformations of peptides with observed crystal structures. vdW volume fragmental constants give accurate estimates of molecular, vdW volume as sum of approximate V_w,xs.     

Ionic Liquids: Dissecting the Enthalpies of Vaporization

We calculate the heats of vaporisation for imidazolium‐based ionic liquids [C_nmim][NTf₂] with n=1, 2, 4, 6, 8 by means of molecular dynamics (MD) simulations and discuss their behavior with respect to temperature and the alkyl chain length. We use a force field developed recently. The different cohesive energies contributing to the overall heats of vaporisations are discussed in detail. With increasing alkyl chain length, the Coulomb contribution to the heat of vaporisation remains constant at around 80 kJ mol^?1, whereas the van der Waals interaction increases continuously. The calculated increase of about 4.7 kJ mol^?1 per CH₂‐group of the van der Waals contribution in the ionic liquid exactly coincides with the increase in the heats of vaporisation for n‐alcohols and n‐alkanes, respectively. The results support the importance of van der Waals interactions even in systems completely composed of ions.     

Adsorption of ions onto polymer surfaces and its influence on zeta potential and adhesion phenomena

 The adhesion behavior that governs many technologically and biologically relevant polymer properties can be investigated by zeta potential measurements with varied electrolyte concentration or pH. In a previous work [1] it was found that the difference of the adsorption free energies of Cl^- and K⁺ ions correlates with the adhesion force caused by van der Waals interactions, and that the decrease of adhesion strength by adsorption layers can be elucidated by zeta potential measurements. In order to confirm these interrelations, zeta potential measurements were combined with atomic force microscopy (AFM) measurements. Force–distance curves between poly(ether ether ketone) and fluorpolymers, respectively, and the Si₃N₄ tip of the AFM device in different electrolyte solutions were measured and analysed. The adsorption free energy of anions calculated from the Stern model correlates with their ability to prevent the adhesion between the polymer surface and the Si₃N₄ tip of the AFM device. These results demonstrate the influence of adsorption phenomena on the adhesion behavior of solids. The results obtained by AFM confirm the thesis that the electrical double layer of solid polymers in electrolyte solutions is governed by ion adsorption probably due to van der Waals interactions and that therefore van der Waals forces can be detected by zeta potential measurements. Received: 18 November 1997 Accepted: 19 January 1998     

Fluorimetric and molecular mechanics study of the inclusion complex of 2-quinoxalinyl-phenoxathiin with β-cyclodextrin

The complex formed by the inclusion of the polarity-sensitive fluorescent probe 2-[2′-quinoxalinyl]-phenoxathiin (QP) into β-cyclodextrin (β-CD) was investigated by steady-state fluorescence spectroscopy in order to confirm the previously stated intramolecular charge transfer nature of the first excited singlet state of QP. A decrease in the emission intensity in the presence of β-CD was observed and explained on this basis. The 1:1 stoichiometry of the inclusion complex and its association constant of 2,223 M⁻¹ were computed. The QP–β-CD complex was further studied by molecular mechanics (MM+ force field), in order to determine its structure and the type of interactions between QP and β-CD. All possible ways QP could penetrate the β-CD cavity were considered and several structures were generated and optimized. The interaction, binding (van der Waals and electrostatic contributions) and perturbation energies were also calculated. The results have showed that the β-CD cavity incorporates the central part of QP and that complexation is mainly due to van der Waals host–guest interactions.     

Adamantylazoles: IV. Acid-Catalyzed Adamantylation of Pyrazoles

Pyrazoles with pK _{B H} ⁺ no more than 0.8 and having substituents in 3(5) position with effective van der Waals radii not exceeding 2 Å in a mixture of phosphoric and acetic acids at weight ratio 4:1 (H ₀ -1,8) react with 1-adamantanol to afford the corresponding 1-(1-adamantyl)- or 1,4-di(1-adamantyl)pyrazoles.     

On the spatial structure of methyl 6,7-endo, sin-dibrom-7-anti-(phenylsulfonyl) bicyclo[3.1.1]heptane-6-exo-carboxylate

In the ¹ H and ¹³ C NMR spectra of methyl 6,7-endo,sin-dibromo-7-anti-(phenylsulfonyl)bicycle-[3.1.1]heptane-6-exo-carboxylate, H(1) and H(5) protons as well as C(1) and C(5) carbon atoms show their chemical inequivalence determined by the hindered rotation of sulfonyl and ester groups about simple C-S and C-C bonds due to the existence of donor-acceptor interaction between the carbonyl C atom and the oxygen atom of the SO₂Ph group. This interaction is indicated by the single crystal X-ray diffraction study detecting the shortened intramolecular contacts (2.49 ? with the sum of the C…O van der Waals radii of 3.00 ?). Other features of the norpinane skeleton conformation and the spatial orientation of substituents in the single crystal are discussed. By ¹ H NMR methods, the parameters of the dependence of molecular conformations on the temperature of DMSO-d ₆ solution and the activation free energy △G _c ^≠ = 80.1 kJ/mol of conformational transitions are determined. By a quantum chemical DFT calculation of the potential energy surface it is revealed that the hindered rotation of the ester group makes the main contribution to the barrier of conformational transitions.     

Anisotropy of the van der Waals Configuration of Atoms in Complex,Condensed, and Gas-Phase Molecules

Anisotropic van der Waals (vdW) radii of 5b–7bsubgroup elements were determined from structures of gas-phase van der Waals complexes and crystal molecular compounds. The anisotropy of the van der Waals configuration of atoms was shown to decrease when going from isolated molecules to the condensed state. Variations in intermolecular distances, which are usually explained in terms of the formation of hydrogen bonds, are substantially governed by the anisotropic effect.     

DFT evaluation of the electronic structures and spectroscopic properties of the self-assembled [Pt2M4(C ≡ CH)8] (M=Cu, Ag) clusters

Electronic structures and spectroscopic properties of self-assembled [Pt₂M₄(C≡CH)₈] (M=Cu, Ag) clusters have been studied by the TD-DFT (time-dependent density functional theory) calculations with the polarizable continuum model (PCM). The ground- and excited-state structures were optimized by the DFT (density functional theory) methods. The calculated structures and spectroscopic properties are in agreement with the corresponding experimental results. The [Pt₂Ag₄(C≡CH)₈] clusters have two stable ground state geometries (D ₄ and D _4h symmetry). The calculated Pt-M distances suggest only very weak interactions. The Cu-Cu distances are larger than the van der Waals radii of two Cu atoms and the Ag-Ag distances are analogous with the sum of van der Waals radii of two Ag atoms. Upon excitation, the interaction of Pt⋯M, Ag⋯Ag is strengthened, while the Cu⋯Cu distances are shortened but they are still larger than the sum of van der Waals radii of two Cu atoms. The lowest-energy absorptions are at 450, 365 and 375 nm and the emissions are at 611, 431 and 435 nm for [Pt₂Cu₄(C≡CH)₈], [Pt₂Ag₄(C≡CH)₈] (A) and (B), respectively. The transitions are all perturbed by the Cu or Ag composition through the UV-Vis spectra region; therefore, there are not pure ILCT or M_PtLCT characteristics (ILCT: intraligand charge transfer; MLCT: metal-to-ligand charge transfer) in absorptions of heteropolynuclear [Pt₂M₄(C≡CH)₈] clusters. Since the emissions and the lowest-absorptions have different transition characteristics for each complex, the emissions should not come from the lowest-energy absorptions. Because the M⋯M interactions in the excited state of [Pt₂Ag₄(C≡CH)₈] are augmented, the emissions of [Pt₂Ag₄(C≡CH)₈] clusters bear prominent ILCT character, which is the reason why the emission wavelengths of [Pt₂Ag₄(C≡CH)₈] have a small hypsochromic shift relative to the emission wavelength of homoleptic [Pt(C≡CH)₄]²⁻ precursor.     

Long-Range van der Waals Interactions in Density Functional Theory

The early difficulties in accounting for long-range van der Waals interactions in the framework of density functional theory (DFT) have been overcome to a certain extent in recent works by several groups, and those interactions can be computed numerically. In this paper a derivation of the analytical form of the attractive van der Waals interaction between two neutral atoms with polarizabilities α₁ and α₂ at large distance R, namely E _int=−C ₆ α₁ α₂/R ⁶ is performed within the context of DFT. Use is made of the properties of the Coulomb correlation hole, and it is shown that nonlocal Coulomb correlations are responsible for long-range dispersion interactions.     

Molecular Modeling to Estimate the Diffusion Coefficients of Drugs and Other Small Molecules

Diffusion is a spontaneous process and one of the physicochemical phenomena responsible for molecular transport, the rate of which is governed mainly by the diffusion coefficient; however, few coefficients are available because the measurement of diffusion rates is not straightforward. The translational diffusion coefficient is related by the Stokes–Einstein equation to the approximate radius of the diffusing molecule. Therefore, the stable conformations of small molecules were first calculated by molecular modeling. A simple radius r_s and an effective radius r_e were then proposed and estimated using the stable conformers with the van der Waals radii of atoms. The diffusion coefficients were finally calculated with the Stokes–Einstein equation. The results showed that, for the molecules with strong hydration ability, the diffusion coefficients are best given by r_e and for other compounds, r_s provided the best coefficients, with a reasonably small deviation of ~0.3 × 10⁻⁶ cm²/s from the experimental data. This demonstrates the effectiveness of the theoretical estimation approach, suggesting that diffusion coefficients have potential use as an additional molecular property in drug screening.     

The strength and length of donor-acceptor bonds in molecular complexes

Numerous published data on the structure and thermodynamics of formation of molecular complexes are analyzed. The enthalpies of complexation (−ΔH) are related to the characteristic parameter Δr = [r _DA−a ₁(r _D+r _A)], where r _DA is the donor-acceptor bond length determined by microwave spectroscopy and X-ray analysis, r _D and r _A are the tabulated values of the homopolar covalent radii of the heteroatoms that form the donor-acceptor bond, and a ₁ is an empirical coefficient equal to 0.901±0.007. The relation between −ΔH and Δr values has the form −ΔH = a ₂/Δr (a ₂ = 21.6±1.6 kJ Å mol⁻¹), with a mean relative error of approximation of about 15% and a correlation coefficient of 0.97. As the strength of the complex increases, the donor-acceptor bond length approaches the sum of the heteropolar covalent radii of the atoms involved in the bond (Δr tends to zero). At Δr ≫ 1, the strength of complexes is determined by weak van der Waals interactions between the complex components and the −ΔH values tend to zero. Dedicated to the memory of E. N. Guryanova (1911–2004), a prominent scientist who formulated the basic principles elaborated by her disciples in this review. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1869–1878, October, 2007.     

Rationalizing some experimental facts on the complexation of 2-methyl naphthalenecarboxylate and hydroxypropyled cyclodextrins by molecular mechanics and molecular dynamics

Molecular mechanics (MM) and Molecular dynamics (MD) calculations were applied to study the complexation of 2-Methyl naphthalenecarboxylate (2MN) and 2-hydroxypropyl -α-, -β-, and γ-cyclodextrins (HPCDs) in the presence of water. Results showed that 1:1 complexes of 2MN with modified cyclodextrins are stable and that the non-bonded van der Waals interactions are mainly responsible for the complexation. Theoretical results are in good agreement with fluoresence results and they permit us to explain the signs and quantitative differences of ΔH ⁰ and ΔS ⁰ on the basis of the different cavity sizes and the movement of the guest inside the HPCD cavity. Results also reveal a more favorable complexation when 2MN approaches on its polar side.     

Very short OH?hydrogen bond in l-histidinium difluoride

The crystal structure of C₆H₁₁N₃O₂²⁺·2F²⁻ is reported. The structure contains a fluoride ion strongly H-bonded to a carboxylic O atom, a rare, very strong, hydrogen bond. The donor-acceptor distance is 2.3818(10) Å, the shortest value reported to date, considerably less than the sum of the van der Waals radii of the atoms implicated, as expected from a very strong hydrogen bond. The di-cation has an open conformation. There is an extensive H-bonding network between anions and cations assembling rings on the ac plane and chains in several directions. Two extra intermolecular interactions of the type CH?π are found, exhausting the aromatic π electron system ability to act as a proton acceptor.     

Calculation of alcohol conformations by molecular mechanics

The geometries and energies of simple alcohols were calculated with a molecular mechanics force field. The force field requires the application of the charge interaction model with charges calculated by the CNDO/2 method, the importance of electrostatic interactions for the equilibrium of rotamers about the C-O bond exceeds that of van der Waals interactions. The calculated rotamer populations are discussed with regard to the value of ¹H NMR coupling constants ³JHCOH and other experimental data.     

Molecular Mechanics Study of the Inclusion Complexes of Some 1,2,4-Oxadiazole Derivatives of 3,3′-Bis (1,2,4-Oxadiazol-5(4H)-one) with β-Cyclodextrin

Molecular mechanics calculations were employed to study the inclusion of some 1,2,4-oxadiazol derivatives in β-cyclodextrin in vacuum and in the presence of water as a solvent using MM + force field. The driving forces for complexation in both environments are dominated by nonbonded van der Waals host–guest interactions with little electrostatic contribution. Among 1,2,4-oxadiazole derivatives investigated in this work, 3,3′-bis(1,2,4-oxadiazol-5(4H)-one) (H₂OD) forms the least stable 1:1 complex and the stability increases as the chain length increases.