Molecular Quantum Chemistry Research Articles

Atomistic liquid crystalline structures of discotic bent-core-like mesogens formed by hydrogen bonding and interchain interactions

Integrated atomistic and molecular dynamic simulations are used to characterize the role hydrogen bonding and interchain interactions on structures and phase transitions of novel bent-core-like mesogenic materials that exhibit new self-assembly features, attractive to the development of functional materials. Multi-step simulations were carried out to model phase transitions and various spectra of two complex mesogenic materials formed from acid functionalized azo compounds, 4-[2,3,4-tri(octyloxy)phenylazo] benzoic acid and 4-[2,3,4- tri(heptyloxy)phenylazo] benzoic acid. The simulations contain three consecutive steps, involving molecular quantum chemistry, molecular crystal packing, and super cell molecular dynamics calculations. These two mesogens are supposed to form phasmidic molecular conformers. However, simulations point to the formation of complex discotic bent-core-like liquid crystals with tetramer mesogenic assemblies, in very good agreement with experimental observations. The wide range agreements between simulations and experimental results include transitions of crystal structures to columnar and uniaxial nematic phases, x-ray diffraction patterns of columnar phases, the structure of the two-dimensional complex bent-core-like tetramers, molecular Raman spectra, Raman depolarization spectra, and order parameters of nematic phases. The multi-step simulation methodology and its results shed light on this unique behaviour of plasmids with flexible side chains for simulation design of novel bent-core-like mesogenic materials.

Effects of zwitterionic surfactant adsorption on the component distribution in the crude oil droplet: A molecular simulation study

The intermolecular interaction between various components in crude oil, such as saturates, aromatics, resins, and asphaltenes, and the zwitterionic surfactant 3-(decyldimethylazaniumyl) propane-1-sulfonate (DDPS) are investigated in detail via molecular dynamics (MD) simulation and quantum chemistry calculations. The radial distribution function (RDF) is calculated to reflect the effects of the charged functional group, aromatic ring, and heteroatom on the component distribution and configuration in the crude oil droplet. The additional DDPS molecules could fabricate the well-organized adsorption layer at the crude oil surface to replace the original oil/water interface, leading to the obvious movement of the components in both hydrophobic interior and interfacial layer of crude oil droplet. Furthermore, the reduced density gradient (RDG) method is employed to visualize the intermolecular interaction. It is demonstrated that the complex interaction (hydrophobic, electrostatic, and cation-π interaction) between DDPS molecules and related components should be responsible for the final distribution and configuration of various components in the crude oil/water/DDPS system.

Sila-Ibuprofen.

The synthesis, characterization, biological activity, and toxicology of sila-ibuprofen, a silicon derivative of the most common nonsteroidal anti-inflammatory drug, is reported. The key improvements compared with ibuprofen are a four times higher solubility in physiological media and a lower melting enthalpy, which are attributed to the carbon-silicon switch. The improved solubility is of interest for postsurgical intravenous administration. A potential for pain relief is rationalized via inhibition experiments of cyclooxygenases I and II (COX-I and COX-II) as well as via a set of newly developed methods that combine molecular dynamics, quantum chemistry, and quantum crystallography. The binding affinity of sila-ibuprofen to COX-I and COX-II is quantified in terms of London dispersion and electrostatic interactions in the active receptor site. This study not only shows the potential of sila-ibuprofen for medicinal application but also improves our understanding of the mechanism of action of the inhibition process.

Triple stimuli-responsive supramolecular nanoassembly with mitochondrial targetability for chemophotothermal therapy

Mitochondria play crucial roles in a variety of cellular physiological processes, mitochondria-accumulating drug delivery has drawn pronounced attention in the field of cancer theranostics. Camptothecin (CPT) is a DNA Topoisomerase I inhibitor and exerts a broad-spectrum anticancer profile. Berberine (BBR) is able to perferably enter into cancer cell mitochondria and trigger the cell apoptosis. In this work, CPT and BBR were combined together (CPT-ss-BBR) through GSH-responsible disulfide bond, and then co-assembled with photosensitizer indocyanine green (ICG) into nanodrugs (CPT-ss-BBR/ICG NPs), which was driven through hydrophobic, π-π stacking and especially, electrostatic interactions of anions and cations as found by molecular dynamics simulations and quantum chemistry calculations. Our developed nanodrugs displayed an average size of ~168 nm and showed exceptional instability by irradiation presence, acid condition and high concentration of GSH, thereby eliciting the rapid disassembly and accelerating drug release. The better therapy effect of CPT-ss-BBR/ICG NPs on A549 cells might be attributed to triply stimuli-responsive rapid disassembly, preferable accumulation into mitochondria and combined chemotherapy and photothermal therapy, all of which directly rendered the notable loss of mitochondria membrane potential, high level of reactive oxygen species in cancer cells, accelerated the apoptosis of cancer cells and repressed the growth of tumors.

A combined molecular dynamics and quantum mechanics study on the interaction of Fe3+ and human serum albumin relevant to iron overload disease

The interaction of Fe3+ with blood proteins is very important because it leads to understanding the detrimental effect in biological processes. Molecular dynamic (MD) simulations and quantum chemistry calculations were performed to investigate the complex formation between the human serum albumin (HSA) and Fe3+. MD simulation results predict two binding sites (BSs) of HSA for complex formation including Glu-Arg-Asn-Glu-Cys (BS1) and Lys-Glu-Cys-Cys-Glu-Lys (BS2) amino acids. To investigate the interaction of the corresponding binding sites with Fe3+, quantum chemistry calculations were performed at M06-2X/6-31G(d) level in the water. According to density functional theory calculations, binding constant of Fe3+ to human serum albumin in BS1 (log K = 13.33) is lower than that of BS2 (log K = 18.99), showing higher thermodynamic stability of the HSAFe3+ complex in BS2. Natural bond orbital and quantum theory of atoms in molecules analyses demonstrate that the driving force of the complex formation is electrostatic and partially covalent interactions. The results of this research would be valuable to design a suitable iron-chelating agent for the treatment of iron overload.

Kernel-Based Approximation of the Koopman Generator and Schrödinger Operator.

Many dimensionality and model reduction techniques rely on estimating dominant eigenfunctions of associated dynamical operators from data. Important examples include the Koopman operator and its generator, but also the Schrödinger operator. We propose a kernel-based method for the approximation of differential operators in reproducing kernel Hilbert spaces and show how eigenfunctions can be estimated by solving auxiliary matrix eigenvalue problems. The resulting algorithms are applied to molecular dynamics and quantum chemistry examples. Furthermore, we exploit that, under certain conditions, the Schrödinger operator can be transformed into a Kolmogorov backward operator corresponding to a drift-diffusion process and vice versa. This allows us to apply methods developed for the analysis of high-dimensional stochastic differential equations to quantum mechanical systems.

Optical Clearing of Human Skin Using Polyethylene Glycols

Molecular docking and quantum chemistry (PM6 and DFT/B3LYP) methods have been used to investigate the interaction of a number of biological tissue immersion clearing agents (PEG200, PEG300 and PEG400) with collagen mimetic peptides (GPH) 3 . Correlations between the rate (efficiency) of optical clearing and the energy of complex formation are established.

The effects of amino acid sequence and solvent polarity on the self-assembling of cyclic peptide nanotubes and molecular channel formation inside the lipid bilayer

In this article, the effects of amino acid sequence and solvent polarity on the self-assembling process of cyclic peptides (CPs) were investigated by employing molecular dynamic (MD) simulations and quantum chemistry calculations. As a result, CP dimers are not stable in water, because of hydrogen bond (H-bond) lost between the CP units, while chloroform increases the stability of the CP dimers. MM-PBSA and MM-GBSA calculations confirmed that solvent polarity has an important effect on the stability of the CP dimers. Dynamical behavior of the cyclic peptide nanotubes (CPNTs) in chloroform indicates that CPNTs composed of leucine and phenylalanine are better molecular containers than that of isoleucine. At the next step, the ability of these CPNTs in molecular channel formation inside a fully hydrated DMPC (dimyristoylphosphatidylcholine) bilayer was investigated during 50 ns MD simulations. The obtained results show that only CPNT composed of isoleucine can form a molecular channel inside the DMPC membrane because isoleucine has a greater hydrophobicity than leucine and phenylalanine. This property increases the interactions between the CPNT and lipid residues, which elevates the stability of the CPNT inside the DMPC bilayer. Quantum chemistry calculations and non-covalent interactions analysis indicate that the solvent changes the stability and dynamical behavior of the CPNTs through the change in the H-bond strength. Finally, according to the different analyses, it can be concluded that the amino acid sequence in the CP units has an important role in designing specific nanostructures.

XO-PBC: An Accurate and Efficient Method for Molecular Crystals.

In this work, we propose the XO-PBC method, which combines the eXtended ONIOM method (XO) with the periodic boundary condition (PBC) for the description of molecular crystals. XO-PBC tries to embed a finite cluster cut out from the solid into the periodic environment, making it feasible to employ advanced molecular quantum chemistry methods, which are usually prohibitively expensive for direct PBC calculations. In particular, XO-PBC utilizes the results from force calculations to design the scheme to fragment the molecule when crystals are made of large molecules and to select cluster model systems automatically consisting of dimer up to tetramer interactions for embedding. By applying an appropriate theory to each model, a satisfactory accuracy for the system under study is ensured, while a high efficiency is achieved with massively parallel computing by distributing model systems onto different processors. A comparison of the XO-PBC calculations with the conventional direct PBC calculations at the B3LYP level demonstrates its accuracy at substantially low cost for the description of molecular crystals. The usefulness of the XO-PBC method is further exemplified, showing that XO-PBC is able to predict the lattice energies of various types of molecular crystals within chemical accuracy (<4 kJ/mol) when the doubly hybrid density functional XYG3 is used as the target high level and the periodic PBE as the basic low level. The XO-PBC method provides a general protocol that brings the great predictive power of advanced electronic structure methods from molecular systems to the extended solids.

CUBANE HEAT OF FORMATION: CALCULATION METHODS

A comparative analysis of the enthalpies of formation of a cubane calculated by the methods of molecular mechanics and quantum chemistry is carried out. A correlation between the experimental and calculated AM1-method values of the heats of formation of frame hydrocarbons was established, which allowed us to correct the results of calculating the heat of formation of the cubane and reduce the discrepancy with the experimental value of its formation enthalpy to 10.7 kJ / mol.

Hybrid functionals with system‐dependent parameters: Conceptual foundations and methodological developments

AbstractApproximate density‐functional theory (DFT) has become the major workhorse of modern computational chemistry and materials science, but the most widely used DFT approaches, local‐density approximation (LDA) and generalized gradient approximation (GGA), suffer from some fundamental deficiencies, including, in particular, the band gap problem. As a relatively cheap way to overcome the difficulty confronted by LDA/GGA, hybrid functional methods have attracted tremendous interest, first in molecular quantum chemistry, and more recently also in computational materials science. While early hybrid functionals use fixed parameters that are determined either by fitting some standard experimental database or based on theoretical arguments, recent studies have clearly indicated that the hybridization parameters carry on the physical significance and therefore should be system‐dependent. Developing theoretical methods to evaluate those parameters in a first‐principles manner has become one of the most active frontiers in theoretical chemistry community, and various schemes have been proposed. In this article, we aim at giving a systematic overview on the main theoretical concepts underlying various strategies and review major methodological developments in the recent years.This article is categorized under: Structure and Mechanism &gt; Computational Materials Science Electronic Structure Theory &gt; Ab Initio Electronic Structure Methods Electronic Structure Theory &gt; Density Functional Theory

Gaussian Basis Sets for Crystalline Solids: All-Purpose Basis Set Libraries vs System-Specific Optimizations.

It is customary in molecular quantum chemistry to adopt basis set libraries in which the basis sets are classified according to either their size (triple-ζ, quadruple-ζ, ...) and the method/property they are optimal for (correlation-consistent, linear-response, ...) but not according to the chemistry of the system to be studied. In fact the vast majority of molecules is quite homogeneous in terms of density (i.e., atomic distances) and types of bond involved (covalent or dispersive). The situation is not the same for solids, in which the same chemical element can be found having metallic, ionic, covalent, or dispersively bound character in different crystalline forms or compounds, with different packings. This situation calls for a different approach to the choice of basis sets, namely a system-specific optimization of the basis set that requires a practical algorithm that could be used on a routine basis. In this work we develop a basis set optimization method based on an algorithm–similar to the direct inversion in the iterative subspace–that we name BDIIS. The total energy of the system is minimized together with the condition number of the overlap matrix as proposed by VandeVondele et al. [VandeVondele et al. J. Chem. Phys.2007, 227, 114105]. The details of the method are here presented, and its performance in optimizing valence orbitals is shown. As demonstrative systems we consider simple prototypical solids such as diamond, graphene sodium chloride, and LiH, and we show how basis set optimizations have certain advantages also toward the use of large (quadruple-ζ) basis sets in solids, both at the DFT and Hartree–Fock level.

Second-Order Nonlinear Optical Properties of an Amphiphilic Dye Embedded in a Lipid Bilayer. A Combined Molecular Dynamics-Quantum Chemistry Study.

The second harmonic signal of an amphiphilic dye embedded in a lipid bilayer has been calculated by combining molecular dynamics simulations and quantum chemistry calculations based on density functional theory. This computational approach provides insight into the morphology and dynamics of the fully hydrated biological system and the relationships linking the geometry and the environment of the dye to the amplitude of its second-order nonlinear optical response. The results point out a significant enhancement of the dynamic first hyperpolarizability of the dye induced by its interaction with the membrane and highlight the relative importance of dynamical, steric, and electrostatic effects. This computational scheme is thus particularly relevant for rationalizing the nonlinear optical contrasts revealed by second harmonic imaging microscopy of exogenous dyes embedded in biological media.

Association of novel monomethine cyanine dyes with bacteriophage MS2: A fluorescence study

Novel monomethine cyanine dyes Cl-YO, F-YO, Cl-YO-Et, Cl-YO-Bu, and YO-Pent were evaluated as agents to detect and characterise a small virus, the MS2 bacteriophage, using the dye and virus intrinsic fluorescence, kinetic and thermal properties, chemical denaturation, and molecular docking and quantum chemistry modelling. The examined compounds demonstrated enhanced fluorescence responses and high affinities (~1 μM−1) for the intact bacteriophage at physiological ionic strength. The linear Scatchard plots revealed the existence of one binding mode for most dyes. Strong evidence that the cyanines bind to the bacteriophage external surface were obtained, although the possibility of the dye penetration through the virus shell and subsequent complexation with the viral RNA was also tested. The main arguments in favour of the former were that i) the fluorescence of the MS2-bound fluorophores decreased under the influence of protein denaturants, urea and guanidine hydrochloride; ii) the fluorescence responses of the dyes to MS2 and bovine serum albumin were similar; and (iii) one order of magnitude higher sensitivity of the dyes to the yeast RNA was found. Simple docking studies suggested that one cyanine molecule is trapped in a cleft formed by three proteins composing the virus shell. Significant role of electrostatic forces in the stabilisation of the dye-MS2 complexes at low ionic strength (10 mM) was demonstrated, while the influence of steric, hydrophobic, and van-der-Waals interactions was expected to increase at physiological ionic strength. The spectral properties of the novel cyanine dyes compared to other fluorophores demonstrated higher sensitivity of the cyanines to MS2, rendering them promising agents for the investigation of the changes in the virus structure under the influence of heat (Cl-YO-Et, Cl-YO-Bu), denaturants (Cl-YO, F-YO), and ionic strength (all the compounds).

Effect of solvent mixture on the formation of CL-20/HMX cocrystal explosives.

2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20)/1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX) cocrystal is widely concerned due to its high safety and low sensitivity. A CL-20/HMX-solution interface model was constructed to investigate the effect of solvent mixture on cocrystal morphology. The interface models of different solvent mixtures were simulated by molecular dynamics (MD) and quantum chemistry (QC) methods at room temperature. The analyses of binding energy show that CL-20 and HMX molecules are easier to be adsorbed on the cocrystal surface in the presence of solvent mixture dimethyl sulfoxide (DMSO)/acetonitrile (ACN). Mass density distribution and diffusion coefficient analyses demonstrated that the growth of CL-20/HMX cocrystal will be freer in DMSO/ACN. Cooperativity effect analysis shows that the CL-20 binding to HMX is tighter in the presence of DMSO/ACN and the system is more stable. Our findings may provide some guidelines for preparing cocrystal in solvent mixture. Graphical abstract.

Use of molecular dynamics fingerprints (MDFPs) in SAMPL6 octanol-water log P blind challenge.

The in silico prediction of partition coefficients is an important task in computer-aided drug discovery. In particular the octanol-water partition coefficient is used as surrogate for lipophilicity. Various computational approaches have been proposed, ranging from simple group-contribution techniques based on the 2D topology of a molecule to rigorous methods based molecular dynamics (MD) or quantum chemistry. In order to balance accuracy and computational cost, we recently developed the MD fingerprints (MDFPs), where the information in MD simulations is encoded in a floating-point vector, which can be used as input for machine learning (ML). The MDFP-ML approach was shown to perform similarly to rigorous methods while being substantially more efficient. Here, we present the application of MDFP-ML for the prediction of octanol-water partition coefficients in the SAMPL6 blind challenge. The underlying computational pipeline is made freely available in form of the MDFPtools package.

In vivo optical clearing of human skin under the effect of aqueous solutions of some monosaccharides

The results of in vivo optical immersion clearing of human skin under the effect of aqueous solutions of some immersion agents (monosaccharides of ribose, glucose and fructose, as well as glycerol, a triatomic alcohol) were obtained with the use of the OCT method. Values of average velocity of scattering coefficient change, obtained through an averaged A-scan of the OCT signal in the region of derma with the depth of 350 to 700 µm, were determined to evaluate the optical clearing efficiency. The velocity of scattering coefficient change and the optical clearing potential value appeared to be well correlated. The complex molecular modeling of a number of immersion clearing agents with a mimetic peptide of collagen (GPH)3, carried out with the use of the methods of classical molecular dynamics and quantum chemistry, allowed to identify correlations between the optical clearing efficiency and the energy of intermolecular interaction of clearing agents with a collagen peptide fragment.

Accuracy and Resource Estimations for Quantum Chemistry on a Near-Term Quantum Computer.

One of the most important application areas of molecular quantum chemistry is the study and prediction of chemical reactivity. Large-scale, fully error-tolerant quantum computers could provide exact or near-exact solutions to the underlying electronic structure problem with exponentially less effort than a classical computer thus enabling highly accurate predictions for comparably large molecular systems. In the nearer future, however, only "noisy" devices with a limited number of qubits that are subject to decoherence will be available. For such near-term quantum computers the hybrid quantum-classical variational quantum eigensolver algorithm in combination with the unitary coupled-cluster ansatz (UCCSD-VQE) [ Peruzzo et al. Nat. Commun. 2014 , 5 , 4213 and McClean et al. New J. Phys. 2016 , 18 , 023023 ] has become an intensively discussed approach that could provide accurate results before the dawn of error-tolerant quantum computing. In this work we present an implementation of UCCSD-VQE that allows for the first time to treat both open- and closed-shell molecules. We study the accuracy of the obtained energies for nine small molecular systems as well as for four exemplary chemical reactions by comparing to well-established electronic structure methods like (nonunitary) coupled-cluster and density functional theory. Finally, we roughly estimate the required quantum hardware resources to obtain "useful" results for practical purposes.

Thermophysical and electrochemical properties of 1–alkyl–3–(3–butenyl)imidazolium bromide ionic liquids

In this work, a series of ionic liquids (ILs) with unsaturated and variety of different alkyl chain lengths, 1–alkyl–3–(3–butenyl)imidazolium bromide (([RC3 = Cim][Br]), R = methyl (C1), ethyl (C2) or butyl (C4)) were synthesized in order to provide their physical and electrochemical characteristics before any further step are taken involving them on an industrial scale. Thermogravimetric analysis and differential scanning calorimetry were applied to determine their thermal properties. Density and electrical conductivity measurements were performed at atmospheric pressure (p = 0.1 MPa) and in the temperature range from T = (283.15 to 323.15) K and T = (293.15 to 323.15), respectively. The interactions between constituting ions of these pure unsaturated ILs are explored by a combination of experimentally obtained physicochemical properties, as well as molecular dynamics and quantum chemistry.

Cluster-in-Molecule Local Correlation Approach for Periodic Systems.

In this article, the cluster-in-molecule (CIM) local correlation approach for periodic systems with periodic boundary condition has been developed, which allows electron-correlation calculations of various crystals computationally tractable. In this approach, the correlation energy per unit cell of a periodic system can be evaluated as the summation of the correlation contributions from electron-correlation calculations on a series of finite-sized clusters. Each cluster is defined to contain a subset of localized Wannier functions (WFs) (for the occupied space) and projected atomic orbitals (for the virtual space), which can be derived from a periodic Hartree-Fock calculation. Electron-correlation calculations on clusters at second-order Møller-Plesset perturbation theory (MP2) or coupled cluster singles and doubles (CCSD) can be performed with well-established molecular quantum chemistry packages. We perform illustrative calculations at the MP2 and CCSD levels on several types of crystals (neon lattice, carbon monoxide and ammonia crystals, two ionic liquid crystals, and diamond). The results show that CIM is a powerful framework for accurate electron-correlation calculations of crystals.