Intramolecular Energies Research Articles

Theoretical studies on interaction properties of chiral Ru(II) polypyridyl complexes with DNA

Theoretical studies on DNA-photocleavage mechanisms and abilities of chiral Ru(II) polypyridyl complexes have been carried out using the density functional theory (DFT) method. The stable DNA-docking models of chiral Ru(II) polypyridyl complexes were obtained using the docking and DFT methods. Based on the obtained DNA-docking models, the DNA-binding energies of chiral Ru(II) complexes were computed using UB3LYP and UB3LYP-D3 methods, and the trend in DNA-binding affinities of chiral Ru(II) polypyridyl complexes were reasonably explained. According to the distances between complexes and DNA, the reason of DNA-binding abilities of Δ-complexes stronger than those of Λ-complexes was also explained. In addition, the excited-state reduction potentials, electrons-transfer (ET) activation energies and intramolecular reorganization energies of chiral Ru(II) polypyridyl complexes were calculated and the DNA-photocleavage abilities were reasonably explained.

Microwave-Induced Flash Vaporization of Volatile Media: A Preliminary Thrust Generation Study for the Waveguide Pellet Acceleration Concept

This paper describes two intermediate-scale experiments designed to test basic principles of waveguide pellet acceleration, a novel method of using microwave power to generate propulsive thrust from flash vaporization of a “pusher” medium to accelerate a frozen deuterium-tritium fuel pellet. Results from a low-power stage I experiment using a surrogate pusher consisting of an inert medium with volume-distributed metallic particle absorbers are in good agreement with Parks’ wave attenuation theory. In stage II, a high-powered short-pulsed gyrotron source will be used to vaporize a surrogate pusher in a closed system (waveguide/test cell) without an accelerating projectile (pellet) to create a thrust-generating gas of interesting pressures ∼60 to 100 bars and temperatures ∼600 to 1000 K. To compare theory and experiment, the vaporization of various volatile organic compounds with suspended metallic particle absorbers must be examined from a detailed thermodynamic perspective, given that large deviations from ideal-gas behavior arise from the intermolecular forces when these solvents transition from ambient to a dense, warm, supercritical fluid. Using the Peng-Robinson real-gas equation of state, a closed-form expression for the specific internal energy U(V, T) was found that self-consistently includes the intramolecular rotational-vibrational energies, of relevance when measurements of the expanded gas state are taken on timescales faster than the molecular decomposition time. Other thermodynamically significant properties, such as the Joule-Thomson inversion curve, that were calculated from this treatment are in excellent agreement with reported experimental data. This lends further support to the use of surrogate pusher media in place of deuterium.

Applicability of Mulliken's formula for photoinduced and intramolecular charge-transfer energies

The applicability of Mulliken's theory for photoinduced as well as intramolecular charge-transfer states is examined for several systems of interest by comparing its predictions to TDDFT excitation energies, obtained using functionals appropriate for charge-transfer (CT) states. The results show that it is possible to estimate the energy of the CT state of a donor–acceptor pair on the basis of information on the separate donor and acceptor moieties, along with structural data, within 0.3eV of TDDFT values. The novelty and usefulness of the proposed method lies mainly in PET applications where the TDDFT determination of the CT state is challenging.

Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell

In this study, five new biscoumarin derivatives (1–5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48h treatment at different concentration (1, 5 and 10μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular OH⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

Hydroxyalkoxy radicals: importance of intramolecular hydrogen bonding on chain branching reactions in the combustion and atmospheric decomposition of hydrocarbons.

During both the atmospheric oxidation and combustion of volatile organic compounds, sequential addition of oxygen can lead to compounds that contain multiple hydrogen-bonding sites. The presence of two or more of these sites on a hydrocarbon introduces the possibility of intramolecular H-bonding, which can have a stabilizing effect on the reactants, products, and transition states of subsequent reactions. The present work compares the absolute energies of two sets of conformations, those that contain intramolecular H-bonds and those that lack intramolecular H-bonds, for each reactant, product, and transition state species in the 1,2 through 1,7 H-migrations and Cα-Cβ, Cα-H, and Cα-OH-bond scission reactions in the n-hydroxyeth-1-oxy through n-hydroxyhex-1-oxy radicals, for n ranging from 1 to 6. The difference in energy between the two conformations represents the balance between the stabilizing effects of H-bonds and the steric cost of bringing the two H-bonding sites together. The effect of intramolecular H-bonding and the OH group is assessed by comparing the net intramolecular H-bond stabilization energies, the reaction enthalpies, and barrier heights of the n-hydroxyalkoxy radical reactions with the corresponding alkoxy radicals values. The results suggest that there is a complex dependence on the location of the two H-bonding groups, the location of the abstraction or bond scission, and the shape of the transition state that dictates the extent to which intramolecular H-bonding effects the relative importance of H-migration and bond scission reactions for each n-hydroxyalkoxy radical. These findings have important implications for future studies on hydrocarbons with multiple H-bonding sites.

Factors driving the self-assembly of water-soluble calix[4]arene and gemini guests: a combined solution, computational and solid-state study

Negatively charged gemini guests in the presence of a tetracationic host trigger the formation of self-assembling structures at physiological pH in water generating entities of the HG and H2G type (H = host and G = guest). ITC measurements show that the gemini guests are included via concerted electrostatic and hydrophobic interactions and that the formation of the HG adduct is enthalpically driven while the formation of the capsular entity (H2G) is driven by entropy gain. It is shown that the efficiency of capsule formation is influenced by the number of –CH2– units contained in the spacer and that spacers with an even number of methylene groups seem to be the best templating agents. In line with the above picture, MD simulations and DFT calculations show that the entropic contribution strongly depends on the length of the polymethylenic spacer. In the solid state, for the HG assembly three different structures are revealed by single crystal X-ray diffraction; the flexible interacting units create multiple interactions reaching the optimum balance between inter- and intramolecular energies. To the best of our knowledge, these are the first structures ever reported for water-soluble calixarenes and organic anions.

Collisional energy transfer in highly excited molecules.

The excitation/de-excitation step in the Lindemann mechanism is investigated in detail using model development and classical trajectory studies based on a realistic potential energy surface. The model, based on a soft-sphere/line-of-centers approach and using elements of Landau-Teller theory and phase space theory, correctly predicts most aspects of the joint probability distribution P(ΔE,ΔJ) for the collisional excitation and de-excitation process in the argon-allyl system. The classical trajectories both confirm the validity of the model and provide insight into the energy transfer. The potential employed was based on a previously available ab initio intramolecular potential for the allyl fit to 97418 allyl electronic energies and an intermolecular potential fit to 286 Ar-allyl energies. Intramolecular energies were calculated at the CCSD(T)/AVTZ level of theory, while intermolecular energies were calculated at the MP2/AVTZ level of theory. Trajectories were calculated for each of four starting allyl isomers and for an initial rotational level of Ji = 0 as well as for Ji taken from a microcanonical distribution. Despite a dissimilarity in Ar-allyl potentials for fixed Ar-allyl geometries, energy transfer properties starting from four different isomers were found to be remarkably alike. A contributing factor appears to be that the orientation-averaged potentials are almost identical. The model we have developed suggests that most hydrocarbons should have similar energy transfer properties, scaled by differences in the potential offset of the atom-hydrogen interaction. Available data corroborate this suggestion.

Theoretical studies on DNA-photocleavage efficiency and mechanism of functionalized Ru(II) polypyridyl complexes.

Theoretical studies on the DNA-photocleavage mechanism and efficiency of some Ru(II) polypyridyl complexes as novel reagents have been carried out using the density functional theory (DFT) method. Stable DNA-docking models of Ru(II) polypyridyl complexes were obtained using the docking and DFT methods. The excited-state reduction potentials, electron-transfer (ET) activation energies, and intramolecular reorganization energies were theoretically calculated, and the corresponding frontier molecular orbitals of complexes were also presented. Based on these properties of excited states, the essential component of two different DNA-photocleavage mechanisms, i.e., the photoinduced oxidation-reduction mechanism and the singlet oxygen photosensitization mechanism, has been revealed, and the DNA-photocleavage efficiencies were reasonably explained, and hereby a complex with excellent DNA-photocleavage ability was also designed. This work offers valuable theoretical insight into the property of excited-states and the DNA-photocleavage mechanism of Ru(II) polypyridyl complexes as novel reagents.

Theoretical study of the substituent effects on O–H BDE of trans-resveratrol derivatives in water and benzene: NBO analysis of intramolecular hydrogen bonds

The effect of solvents and intramolecular hydrogen bonds on the three O–H bond dissociation enthalpies (BDEs) of non-substituted and substituted trans-resveratrols has been studied in water and benzene using DFT/B3LYP method. The formation of strong intramolecular hydrogen bonds in several radicals results in low BDEs. The solvent alters the intramolecular hydrogen bonds stabilization energies. In electron-withdrawing groups where the substituent causes high polarity of the parents and especially radicals, the effect of the solvent is stronger. When the substitution has a poor effect on the resveratrol molecule, the solvent has weak influence on formed radical stability, too. Besides intramolecular hydrogen bonds, the position, as well as electron-donating or electron-withdrawing character of a substituent in both, polar or nonpolar solvents, is able to affect OH BDEs substantially.

Is the equilibrium composition of mechanochemical reactions predictable using computational chemistry?

The ability of computational methods to predict the structures and energetics that determine the equilibrium of solid state mechanochemical reactions has been assessed. Two previously characterised base-catalysed metathesis reactions between aromatic disulfides are studied using crystal structure prediction methods and lattice energy calculations that combine molecular electronic structure methods with anisotropic atom-atom potentials. We find that lattice energy searches locate three of the six crystal structures as global minima on their respective crystal energy landscapes. The remaining structures are less successfully predicted, due to problems modelling relative conformational energies due to limitations of the density functional theory method for calculating intramolecular energies. Prediction of the overall reaction energies proves challenging for current methods, but the results show promise as a base on which to build more accurate and reliable approaches.

Are racemic crystals favored over homochiral crystals by higher stability or by kinetics? Insights from comparative studies of crystalline stereoisomers.

The crystal and molecular structures of 134 pairs of diastereoisomers and of 279 racemic-homochiral pairs were retrieved from the Cambridge Structural Database. Lattice and intramolecular energies are calculated. Density differences between crystals of stereoisomers of all kind are mostly within 5%, as observed also for crystal polymorphs. Racemic crystals are predominantly, but not exclusively, more stable and more dense. Denser crystals are predominantly more stable, but there is no quantitative correlation between density and energy differences between partners in the chosen pairs. Second-order symmetry operators are neither ubiquitous in the racemic nor patently superior to first-order operators in promoting crystal cohesion. Thermodynamic, energetic factors in the final crystalline products are not enough to explain the (largely) predominant occurrence of racemic crystallization from racemic solution. At least for homogeneous nucleation, a probabilistic factor, from kinetics or from statistical predominance of mixed versus enantiopure aggregates, must be in action during the early separation of liquid-like particles, which are thought to be the precursors of crystal nucleation.

Exploration of zeroth-order wavefunctions and energies as a first step toward intramolecular symmetry-adapted perturbation theory

Non-covalent interactions occur between and within all molecules and have a profound impact on structural and electronic phenomena in chemistry, biology, and material science. Understanding the nature of inter- and intramolecular interactions is essential not only for establishing the relation between structure and properties, but also for facilitating the rational design of molecules with targeted properties. These objectives have motivated the development of theoretical schemes decomposing intermolecular interactions into physically meaningful terms. Among the various existing energy decomposition schemes, Symmetry-Adapted Perturbation Theory (SAPT) is one of the most successful as it naturally decomposes the interaction energy into physical and intuitive terms. Unfortunately, analogous approaches for intramolecular energies are theoretically highly challenging and virtually nonexistent. Here, we introduce a zeroth-order wavefunction and energy, which represent the first step toward the development of an intramolecular variant of the SAPT formalism. The proposed energy expression is based on the Chemical Hamiltonian Approach (CHA), which relies upon an asymmetric interpretation of the electronic integrals. The orbitals are optimized with a non-hermitian Fock matrix based on two variants: one using orbitals strictly localized on individual fragments and the other using canonical (delocalized) orbitals. The zeroth-order wavefunction and energy expression are validated on a series of prototypical systems. The computed intramolecular interaction energies demonstrate that our approach combining the CHA with strictly localized orbitals achieves reasonable interaction energies and basis set dependence in addition to producing intuitive energy trends. Our zeroth-order wavefunction is the primary step fundamental to the derivation of any perturbation theory correction, which has the potential to truly transform our understanding and quantification of non-bonded intramolecular interactions.

Minimizing Density Functional Failures for Non-Covalent Interactions Beyond van der Waals Complexes

CONSPECTUS: Kohn-Sham density functional theory offers a powerful and robust formalism for investigating the electronic structure of many-body systems while providing a practical balance of accuracy and computational cost unmatched by other methods. Despite this success, the commonly used semilocal approximations have difficulties in properly describing attractive dispersion interactions that decay with R(-6) at large intermolecular distances. Even in the short to medium range, most semilocal density functionals fail to give an accurate description of weak interactions. The omnipresence of dispersion interactions, which are neglected in the most popular electronic structure framework, has stimulated intense developments during the past decade. In this Account, we summarize our effort to develop and implement dispersion corrections that dramatically reduce the failures of both inter- and intramolecular interaction energies. The proposed schemes range from improved variants of empirical atom pairwise dispersion correction (e.g., dD10) to robust formulations dependent upon the electron density. Emphasis has been placed on introducing more physics into a modified Tang and Toennies damping function and deriving accurate dispersion coefficients. Our most sophisticated and established density-dependent correction, dDsC, is based on a simple generalized gradient approximation (GGA)-like reformulation of the exchange hole dipole moment introduced by Becke and Johnson. Akin to its empirical precursor, dDsC dramatically improves the interaction energy of a variety of standard density functionals simultaneously for typical intermolecular complexes and shorter-range interactions occurring within molecules. The broad applicability and robustness of the dDsC scheme is demonstrated on various representative reaction energies, geometries, and molecular dynamic simulations. The suitability of the a posteriori correction is also established through comparisons with the more computationally demanding self-consistent implementation. The proposed correction is then exploited to identify the key factors at the origin of the errors in thermochemistry beyond van der Waals complexes. Particular focus is placed on charge-transfer and mixed-valence complexes, which are relevant to the field of organic electronics. These types of complexes represent insightful examples for which the delocalization error may partially counterbalance the missing dispersion. Our devised methodology reveals the true performance of standard density functional approximations and the subtle interplay between the two types of errors. The analysis presented provides guidance for future functional development that could further improve the modeling of the structures and properties of molecular materials. Overall, the proposed state-of-the-art approaches have contributed to stress the crucial role of dispersion and improve their description in both straightforward van der Waals complexes and more challenging chemical situations. For the treatment of the latter, we have also provided relevant insights into which type of density functionals to favor.

Molecular parameters for gas chromatographic identification of E- and Z-isomers of unsaturated compounds

The use of the previously proposed parameter U proportional to the vibrational component of intramolecular energies, which can be considered as a kind of molecular topological characteristics, enables the estimation of gas chromatographic retention indices of isomeric unsaturated compounds. The latter include both isomers differing in the position of C=C double bonds in the carbon skeleton of the molecules and isomers with different configurations of these bonds (E and Z).

Coupled cluster, MP2, and DFT study of structures, stabilities, vibrations, and bonding properties of XXeOH (X = F, Cl, Br, and I)

The optimized geometries, molecular properties, and stabilities of new noble gas molecules, XXeOH (X = F, Cl, Br, and I), were studied using CCSD, MP2, CAM-B3LYP, and WB97XD methods and large basis sets. All XXeOH molecules showed equilibrium structures with Cs symmetry. The results also showed that some bonds in XXeOH could be presented as a typical ionic bond. An alteration in ion-pair character was observed for IXeOH, showing two OH− and IXe+ parts, while in other molecules, they could be presented as XeOH+ and X−. Two decomposition routes were proposed for these molecules that showed high exothermic reactions. However, despite their low thermodynamic stabilities, their decomposition rate constants were small and all molecules (except BrXeOH) had high kinetic stabilities, indicating the possibility for identification and characterization of these molecules. However, in addition to the calculation of their vibrational frequencies, NBO atomic charges, and hybridizations, the bonding properties of XXeOH molecules were studied by AIM calculations (to calculate electron densities, bond elipticities, and Laplacian of electron densities) and second-order intramolecular perturbation energies using NBO calculations. Moreover, the ease of formations and relative stabilities of XXeOH molecules were compared using heats of formations, Gibbs free energies of formations and isodesmic reactions. These calculations showed that the stability of XXeOH molecules was decreased from F to I.

In silico identification of the active conformation of open-chain enaminones with anticonvulsant activity

A study about the relationship between molecular properties of open-chain enaminones and their anticonvulsant activity is presented in this paper. Geometry optimizations of the enaminones were performed at HF and DFT/B3LYP levels of theory using 6-31 + G(d) basis set. The HOMO and LUMO energies were obtained at the same level of theory. The solvent effect was studied through IPCM. A natural bond orbital (NBO) analysis was performed to analyze the possible association between the stability and the intramolecular hydrogen bond interaction energies. The stability order of the isomers in gas phase was the following: cis-1 > trans-4 > cis-2 > trans-3. The IPCM method showed that the trans-3 isomers are more stable that the cis-2 when the solvent effect was taken into account. Two important intramolecular hydrogen bonds were found by NBO analysis. According to our findings, these interactions could affect the activity of the two most stable isomers (cis-1 and trans-4). By contrast, trans-3 isomers did not present this type of interaction. Therefore, the latter isomers have a large flexibility and can adopt a conformation similar to the conformation of active ringed enaminones. In addition, HOMO and LUMO energies suggested that the trans-3 isomers could be the most reactive species.

Three-Dimensional RISM Integral Equation Theory for Polarizable Solute Models.

Modeling solute polarizability is a key ingredient for improving the description of solvation phenomena. In recent years, polarizable molecular mechanics force fields have emerged that circumvent the limitations of classical fixed charge force fields by the ability to adapt their electrostatic potential distribution to a polarizing environment. Solvation phenomena are characterized by the solute's excess chemical potential, which can be computed by expensive fully atomistic free energy simulations. The alternative is to employ an implicit solvent model, which poses a challenge to the formulation of the solute-solvent interaction term within a polarizable framework. Here, we adapt the three-dimensional reference interaction site model (3D RISM) integral equation theory as a solvent model, which analytically yields the chemical potential, to the polarizable AMOEBA force field using an embedding cluster (EC-RISM) strategy. The methodology is analogous to our earlier approach to the coupling of a quantum-chemical solute description with a classical 3D RISM solvent. We describe the conceptual physical and algorithmic basis as well as the performance for several benchmark cases as a proof of principle. The results consistently show reasonable agreement between AMOEBA and quantum-chemical free energies in solution in general and allow for separate assessment of energetic and solvation-related contributions. We find that, depending on the parametrization, AMOEBA reproduces the chemical potential in better agreement with reference quantum-chemical calculations than the intramolecular energies, which suggests possible routes toward systematic improvement of polarizable force fields.

Reaction Dynamics of CH3+ HBr → CH4+ Br at 150-1000 K

The kinetics of the radical-polar molecule reaction CH3 + HBr → CH4 + Br has been studied at temperatures between 150 and 1000 K using classical dynamics procedures. Potential energy surfaces constructed using analytical forms of inter- and intramolecular interaction energies show a shallow well and barrier in the entrance channel, which affect the collision dynamics at low temperatures. Different collision models are used to distinguish the reaction occurring at low- and high-temperature regions. The reaction proceeds rapidly via a complex-mode mechanism below room temperature showing strong negative temperature dependence, where the effects of molecular attraction, H-atom tunneling and recrossing of collision complexes are found to be important. The temperature dependence of the rate constant between 400 and 1000 K is positive, the values increasing in accordance with the increase of the mean speed of collision. The rate constant varies from 7.6 × 10 −12 at 150 K to 3.7 × 10 −12 at 1000 K via a minimum value of 2.5 × 10 −12 cm 3 molecule −1 s −1 at 400 K.

Molecular Dynamics Simulations to Provide Insights into Epitopes Coupled to the Soluble and Membrane-Bound MHC-II Complexes

Epitope recognition by major histocompatibility complex II (MHC-II) is essential for the activation of immunological responses to infectious diseases. Several studies have demonstrated that this molecular event takes place in the MHC-II peptide-binding groove constituted by the α and β light chains of the heterodimer. This MHC-II peptide-binding groove has several pockets (P1-P11) involved in peptide recognition and complex stabilization that have been probed through crystallographic experiments and in silico calculations. However, most of these theoretical calculations have been performed without taking into consideration the heavy chains, which could generate misleading information about conformational mobility both in water and in the membrane environment. Therefore, in absence of structural information about the difference in the conformational changes between the peptide-free and peptide-bound states (pMHC-II) when the system is soluble in an aqueous environment or non-covalently bound to a cell membrane, as the physiological environment for MHC-II is. In this study, we explored the mechanistic basis of these MHC-II components using molecular dynamics (MD) simulations in which MHC-II was previously co-crystallized with a small epitope (P7) or coupled by docking procedures to a large (P22) epitope. These MD simulations were performed at 310 K over 100 ns for the water-soluble (MHC-IIw, MHC-II-P7w, and MHC-II-P22w) and 150 ns for the membrane-bound species (MHC-IIm, MHC-II-P7m, and MHC-II-P22m). Our results reveal that despite the different epitope sizes and MD simulation environments, both peptides are stabilized primarily by residues lining P1, P4, and P6-7, and similar noncovalent intermolecular energies were observed for the soluble and membrane-bound complexes. However, there were remarkably differences in the conformational mobility and intramolecular energies upon complex formation, causing some differences with respect to how the two peptides are stabilized in the peptide-binding groove.

Synthesis and physicochemical properties of polyhydroxylated diphenyl ethers

Five polyhydroxylated diphenyl ethers (PHODEs) were synthesized. The first ionization constants (pKa1) of the synthesized compounds and seven phenolic compounds were determined using potentiometric titration experiments, together with the software ACD/Labs pKa DB program (version 6.0). The compared results showed that the software could be used to predict the pKa1 of all 209 PHODEs. The thermodynamic properties of 209 PHODEs were calculated using density functional theory (DFT) at the B3LYP/6-311G** level with Gaussian 09 program. The standard enthalpy of formation (ΔfHθ) and the standard Gibbs energy of formation (ΔfGθ) were obtained. Two types of hydrogen bond were found to exist in the PHODEs’ molecules. The intramolecular hydrogen bond energies were discussed. The relative stability of PHODEs isomers was proposed theoretically with the relative standard Gibbs energy of formation (ΔfGRθ). The relationships of Sθ, ΔfHθ and ΔfGθ to the number and position of the hydroxyl substitution (NPHOS) were studied.