Computational benchmark for calculation of silane and siloxane thermochemistry

Geometries of model chlorosilanes, R₃SiCl, silanols, R₃SiOH, and disiloxanes, (R₃Si)₂O, R?=?H, Me, as well as the thermochemistry of the reactions involving these species were modeled using 11 common density functionals in combination with five basis sets to examine the accuracy and applicability of various theoretical methods in organosilicon chemistry. As the model reactions, the proton affinities of silanols and siloxanes, hydrolysis of chlorosilanes and condensation of silanols to siloxanes were considered. As the reference values, experimental bonding parameters and reaction enthalpies were used wherever available. Where there are no experimental data, W1 and CBS-QB3 values were used instead. For the gas phase conditions, excellent agreement between theoretical CBS-QB3 and W1 and experimental thermochemical values was observed. All DFT methods also give acceptable values and the precision of various functionals used was comparable. No significant advantage of newer more advanced functionals over ‘classical’ B3LYP and PBEPBE ones was noted. The accuracy of the results was improved significantly when triple-zeta basis sets were used for energy calculations, instead of double-zeta ones. The accuracy of calculations for the reactions in water solution within the SCRF model was inferior compared to the gas phase. However, by careful estimation of corrections to the ΔH_solv and ΔG_solv of H⁺ and HCl, reasonable values of thermodynamic quantities for the discussed reactions can be obtained.     

Supramolecular rods via halogen bonding-based self-assembly of fluorinated phosphazene nanopillars

A cyclotriphosphazene derivative bearing six 4-iodotetrafluorophenyl-substituted arms self-assembles with dipyridyl derivatives under the control of N?I halogen bonding to give rise to complexes where the starting modules are present in a 1:3 stoichiometric ratio, respectively. The directionality of the N?I halogen bonding translates the pillar-like arrangement adopted by the cyclotriphosphazene module into the rod-shaped supramolecular structure of the formed infinite chains. The invariance of N?I interactions translates the different size of the used dipyridyl modules into different pitches along the self-assembled rods. The obtained supramolecular architectures show a remarkable structural similarity confirming the reliability of halogen bonding in the design of complex supramolecular networks.     

Interaction of glucosamine with uracil and thymine: a computational study

Noncovalent interactions are ubiquitous and have been well recognized in chemistry, biology and material science. Yet, there are still recurring controversies over their natures, due to the wide range of noncovalent interaction terms. In this Essay, we employed the Valence Bond (VB) methods to address two types of interactions which recently have drawn intensive attention, i.e., the halogen bonding and the CH???HC dihydrogen bonding. The VB methods have the advantage of interpreting molecular structures and properties in the term of electron-localized Lewis (resonance) states (structures), which thereby shed specific light on the alteration of the bonding patterns. Due to the electron localization nature of Lewis states, it is possible to define individually and measure both polarization and charge transfer effects which have different physical origins. We demonstrated that both the ab initio VB method and the block-localized wavefunction (BLW) method can provide consistent pictures for halogen bonding systems, where strong Lewis bases NH₃, H₂O and NMe₃ partake as the halogen bond acceptors, and the halogen bond donors include dihalogen molecules and XNO₂ (X?=?Cl, Br, I). Based on the structural, spectral, and energetic changes, we confirm the remarkable roles of charge transfer in these halogen bonding complexes. Although the weak C-H???H-C interactions in alkane dimers and graphane sheets are thought to involve dispersion only, we show that this term embeds delicate yet important charge transfer, bond reorganization and polarization interactions.

     

Discovering the intelligence in molecular biology

The Third International Conference on Intelligent Systems in Molecular Biology was truly an outstanding event. Computational methods in molecular biology have reached a new level of maturity and utility, resulting in many high-impact applications. The success of this meeting bodes well for the rapid and continuing development of computational methods, intelligent systems and information-based approaches for the biosciences. The basic technology, originally most often applied to ‘feasibility’ problems, is now dealing effectively with the most difficult real-wold problems. Significant progress has been made in understanding protein-structure information, structural classification, and how functional information and the relevant features of active-site geometry can be gleaned from structures by automated computational approaches. The value and limits of homology-based methods, and the ability to classify proteins by structure in the absence of homology, have reached a new level of sophistication. New methods for covariation analysis in the folding of large structures such as RNAs have shown remarkably good results, indicating the long-term potential to understand very complicated molecules and multimolecular complexes using computational means. Novel methods, such as HMMs, context-free grammars and the uses of mutual information theory, have taken center stage as highly valuable tools in our quest to represent and characterize biological information. A focus on creative uses of intelligent systems technologies and the trend toward biological application will undoubtedly continue and grow at the 1996 ISMB meeting in St Louis.     

Atomistic simulations of materials for optical chemical sensors: DFT-D calculations of molecular interactions between gas-phase analyte molecules and simple substrate models

The structures of complexes of some small molecules (formaldehyde, acetaldehyde, ammonia, methylamine, methanol, ethanol, acetone, benzene, acetonitrile, ethyl acetate, chloroform, and tetrahydrofuran, considered as possible analytes) with ethylbenzene and silanol (C₆H₅C₂H₅ and SiH₃OH, considered as models of polystyrene and silica gel substrates) and with acridine (C₁₃H₉N, considered as a model of an indicator dye molecule of the acridine series) and the corresponding interaction energies have been calculated using the DFT-D approximation. The PBE exchange-correlation potential was used in the calculations. The structures of complexes between the analyte and the substrate were determined by optimizing their ground-state geometry using the SVP split-valence double-zeta plus polarization basis set. The complex formation energies were refined by single-point calculations at the calculated equilibrium geometries using the sufficiently large triple-zeta TZVPP basis set. The calculated interaction energies are used to assess the possibility of using dyes of the acridine series adsorbed on a polystyrene or silica substrate for detecting the small molecules listed above.     

A knowledge-based halogen bonding scoring function for predicting protein-ligand interactions

Halogen bonding, a non-covalent interaction between the halogen σ-hole and Lewis bases, could not be properly characterized by majority of current scoring functions. In this study, a knowledge-based halogen bonding scoring function, termed XBPMF, was developed by an iterative method for predicting protein-ligand interactions. Three sets of pairwise potentials were derived from two training sets of protein-ligand complexes from the Protein Data Bank. It was found that two-dimensional pairwise potentials could characterize appropriately the distance and angle profiles of halogen bonding, which is superior to one-dimensional pairwise potentials. With comparison to six widely used scoring functions, XBPMF was evaluated to have moderate power for predicting protein-ligand interactions in terms of “docking power”, “ranking power” and “scoring power”. Especially, it has a rather satisfactory performance for the systems with typical halogen bonds. To the best of our knowledge, XBPMF is the first halogen bonding scoring function that is not dependent on any dummy atom, and is practical for high-throughput virtual screening. Therefore, this scoring function should be useful for the study and application of halogen bonding interactions like molecular docking and lead optimization.

Supramolecular platinum complexes for cancer therapy

The rise of supramolecular chemistry offers new tools to design therapeutics and delivery platforms for biomedical applications. This review aims to highlight the recent developments that harness host-guest interactions and self-assembly to design novel supramolecular Pt complexes as anticancer agents and drug delivery systems. These complexes range from small host-guest structures to large metallosupramolecules and nanoparticles. These supramolecular complexes integrate the biological properties of Pt compounds and novel supramolecular structures, which inspires new designs of anticancer approaches that overcome problems in conventional Pt drugs. Based on the differences in Pt cores and supramolecular structures, this review focuses on five different types of supramolecular Pt complexes, and they include host-guest complexes of the FDA-approved Pt(II) drugs, supramolecular complexes of nonclassical Pt(II) metallodrugs, supramolecular complexes of fatty acid-like Pt(IV) prodrugs, self-assembled nanotherapeutics of Pt(IV) prodrugs, and self-assembled Pt-based metallosupramolecules.     

Towards the Accurate and Efficient Calculation of Optical Rotatory Dispersion Using Augmented Minimal Basis Sets

It has been recognized that quantum‐chemical predictions of dispersive (nonresonant) chiroptical phenomena are exquisitely sensitive to the periphery of the electronic wavefunction. To further elaborate and potentially exploit this assertion, linear‐response calculations of specific optical rotation were performed within the framework of density‐functional theory (DFT) by augmenting small basis sets (e.g., STO ‐ 3G and 3 ‐ 21G) for the core and valence electrons with diffuse functions taken from substantially larger bases (e.g., aug‐cc‐pVXZ where X = D, T, or Q). Of particular interest was the ability of such computationally efficient (augmented small‐basis) model chemistries to reproduce results derived from more expensive (canonical large‐basis) schemes. The results appear to be quite promising, with the augmented minimal‐basis ansatz often yielding wavelength‐resolved rotatory powers close to those deduced from standard DFT(B3LYP)/aug‐cc‐pVXZ treatments. Analogous linear‐response analyses were performed by means of coupled‐cluster singles and doubles (CCSD) theory, once again leading to augmented small‐basis estimates of specific rotation in reasonable accord with their large‐basis counterparts. Although CCSD predictions were deemed to be slightly worse than those obtained from DFT, they still were of sufficient quality for such reduced‐basis calculations to be considered viable for exploratory work. Chirality 25:606–616, 2013. © 2013 Wiley Periodicals, Inc.     

Halogen–water–hydrogen bridges in biomolecules

The importance of water in biological systems has long been recognized in chemistry and biology communities. In this article we describe a new manner by which water affects biomolecular behaviors, called halogen–water–hydrogen bridge (XWH bridge), that is, one hydrogen bonding (H-bonding) in water-mediated H-bond bridge is replaced by halogen bonding (X-bonding). Although behaving similarly to water-mediated H-bond motif, the XWH bridge usually stands in multifurcated forms and possesses stronger directionality. Quantum mechanical analysis on several model and real systems reveals that the XWH bridges are more thermodynamically stable than other water-involved interactions, and this stability is further enhanced by the cooperation of X-bonding and H-bonding. Crystal structure survey clearly demonstrates the significance of XWH bridges in stabilization of biomolecular conformations and in mediation of protein–protein, protein–nucleic acid, and receptor–ligand recognition and binding. These findings shed light into the potential value of XWH bridges in drug design and biological engineering.     

Recent developments in computational and experimental studies of physicochemical properties of Au and Ag nanostructures on cellular uptake and nanostructure toxicity

Recent developments in studies of the uptake and toxicity of both gold (Au) and silver (Ag) nanostructures (NS) in drug delivery systems have shown that physicochemical properties play an important role. Physicochemical properties of engineered NS such as size, shape, coordination chemistry, surface charge, and surface chemistry generally manifest in reactivity, surface energetics and electronic properties of the nanomaterials. This review discusses the computational and experimental studies conducted to study the effects of physicochemical properties on cellular uptake and nanostructure toxicity. The studies show that properties like coordination chemistry have often been overlooked when studying the high surface energy of NS.     

Liquid Chromatography Enantioseparations of Halogenated Compounds on Polysaccharide‐Based Chiral Stationary Phases: Role of Halogen Substituents in Molecular Recognition

Halogenated chiral molecules have become important in several fields of science, industry, and society as drugs, natural compounds, agrochemicals, environmental pollutants, synthetic products, and chiral supports. Meanwhile, the perception of the halogen moiety in organic compounds and its role in recognition processes changed. Indeed, the recognition of the halogen bond as an intermolecular interaction occurring when the halogen acts as a Lewis acid had a strong impact, particularly in crystal engineering and medicinal chemistry. Due to this renewed interest in the potentialities of chiral organohalogens, here we focus on selected recent applications dealing with enantioseparations of halogenated compounds on polysaccharide‐based chiral stationary phases (CSPs), widely used in liquid chromatography (LC). In particular, recently the first case of halogen bonding‐driven high‐performance LC (HPLC) enantioseparation was reported on a cellulose‐based CSP. Along with enantioseparations performed under conventional HPLC, representative applications using supercritical fluid chromatography (SFC) are reported. Chirality 27:667–684, 2015. © 2015 Wiley Periodicals, Inc.     

Experimental and theoretical correlations between vanadium K-edge X-ray absorption and K$$\varvec{\beta} $$ emission spectra

A series of vanadium compounds was studied by K-edge X-ray absorption (XAS) and K\(\beta \) X-ray emission spectroscopies (XES). Qualitative trends within the datasets, as well as comparisons between the XAS and XES data, illustrate the information content of both methods. The complementary nature of the chemical insight highlights the success of this dual-technique approach in characterizing both the structural and electronic properties of vanadium sites. In particular, and in contrast to XAS or extended X-ray absorption fine structure (EXAFS), we demonstrate that valence-to-core XES is capable of differentiating between ligating atoms with the same identity but different bonding character. Finally, density functional theory (DFT) and time-dependent DFT calculations enable a more detailed, quantitative interpretation of the data. We also establish correction factors for the computational protocols through calibration to experiment. These hard X-ray methods can probe vanadium ions in any oxidation or spin state, and can readily be applied to sample environments ranging from solid-phase catalysts to biological samples in frozen solution. Thus, the combined XAS and XES approach, coupled with DFT calculations, provides a robust tool for the study of vanadium atoms in bioinorganic chemistry.     

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

In this minireview, we provide an account of the current state-of-the-art developments in the area of mono- and binuclear non-heme enzymes (NHFe and NHFe₂) and the smaller NHFe₍₂₎ synthetic models, mostly from a theoretical and computational perspective. The sheer complexity, and at the same time the beauty, of the NHFe₍₂₎ world represents a challenge for experimental as well as theoretical methods. We emphasize that the concerted progress on both theoretical and experimental side is a conditio sine qua non for future understanding, exploration and utilization of the NHFe₍₂₎ systems. After briefly discussing the current challenges and advances in the computational methodology, we review the recent spectroscopic and computational studies of NHFe₍₂₎ enzymatic and inorganic systems and highlight the correlations between various experimental data (spectroscopic, kinetic, thermodynamic, electrochemical) and computations. Throughout, we attempt to keep in mind the most fascinating and attractive phenomenon in the NHFe₍₂₎ chemistry, which is the fact that despite the strong oxidative power of many reactive intermediates, the NHFe₍₂₎ enzymes perform catalysis with high selectivity. We conclude with our personal viewpoint and hope that further developments in quantum chemistry and especially in the field of multireference wave function methods are needed to have a solid theoretical basis for the NHFe₍₂₎ studies, mostly by providing benchmarking and calibration of the computationally efficient and easy-to-use DFT methods.     

Applicability of PM3 to transphosphorylation reaction path: Toward designing a minimal ribozyme

A growing body of evidence shows that RNA can catalyze many of the reactions necessary both for replication of genetic material and the possible transition into the modern protein-based world. However, contemporary ribozymes are too large to have self-assembled from a prebiotic oligonucleotide pool. Still, it is likely that the major features of the earliest ribozymes have been preserved as molecular fossils in the catalytic RNA of today. Therefore, the search for a minimal ribozyme has been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determine the effects of structural features of the ribozyme on the reaction it catalyzes. Using this model, quantum chemical calculations must be performed to determine quantitatively the effects of structural features on catalysis. Previous studies of the reaction path have been conducted at theab initio level, but these methods are limited to small models due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on the system under investigation. In the preent study we assess the validity of the MNDO/PM3 method on a simple model of the ribozyme-catalyzed reaction, or hydrolysis of phosphoric acid. We find that the results are qualitatively similar toab initio results using large basis sets. Therefore, PM3 is suitable for studying the reaction path of the ribozyme-catalyzed reaction.     

Supramolecular CRISPR-OFF switches with host–guest chemistry

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) technology is a powerful tool in biology and medicine. However, the safety and application of this technology is hampered by excessive activity of CRISPR machinery. It is particularly important to develop methods for switching off CRISPR activity in human cells. The current study demonstrates the concept of supramolecular CRISPR-OFF switches by employing host-guest chemistry. We demonstrate that the CRISPR systems show considerable tolerance to adamantoylation on guide RNAs (gRNAs), whereas supramolecular complexation tremendously affects the function of adamantoyl gRNAs. Host–guest chemistry is demonstrated to be novel and effective tools to reduce unwanted excessive activities of CRISPR complexes in human cells. This work indicates considerable potential of supramolecular strategy for controlling and enhancing CRISPR systems.     

Peptide selectivity between the PDZ domains of human pregnancy‐related serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) can be reshaped by different halogen probes

The human HtrA family of serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) are the key enzymes associated with pregnancy and closely related to the development and progression of many pathological events. Previously, it was found that halogen substitution at the indole moiety of peptide Trp‐1 residue can form a geometrically satisfactory halogen bond with the Drosophila discs large, zona occludens‐1 (PDZ) domain of HtrA proteases. Here, we attempt to systematically investigate the effect of substitution with 4 halogen types and 2 indole positions on the binding affinity and specificity of peptide ligands to the 4 HtrA PDZ domains. The complex structures, interaction energies, halogen‐bonding strength, and binding affinity of domain‐peptide systems were modeled, analyzed, and measured via computational modeling and fluorescence‐based assay. It is revealed that there is a compromise between the local rearrangement of halogen bond involving different halogen atoms and the global optimization of domain‐peptide interaction; the substitution position is fundamentally important for peptide‐binding affinity, while the halogen type can effectively shift peptide selectivity between the 4 domains. The HtrA1‐PDZ and HtrA4‐PDZ as well as HtrA2‐PDZ and HtrA3‐PDZ respond similarly to different halogen substitutions of peptide; –Br substitution at R2‐position and –I substitution at R4‐position are most effective in improving peptide selectivity for HtrA1‐PDZ/HtrA4‐PDZ and HtrA2‐PDZ/HtrA3‐PDZ, respectively; –F substitution would not address substantial effect on peptide selectivity for all the 4 domains. Consequently, the binding affinities of a native peptide ligand DSRIWWV^–COOH as well as its 4 R2‐halogenated counterparts were determined as 1.9, 1.4, 0.5, 0.27, and 0.92 μM, which are basically consistent with computational analysis. This study would help to rationally design selective peptide inhibitors of HtrA family members by using different halogen substitutions.