Quantum Mechanical Level Research Articles

Molecular interactions of praziquantel drug with nanosurfaces of sepiolite and montmorillonite

Praziquantel drug is nowadays in continuo study to overcome adverse biopharmaceutical properties as drug of first choice for the treatment of the human schistosomiasis. Meanwhile, sepiolite and montmorillonite have been studied experimentally as low-cost nanocarrier to design new praziquantel delivery systems. In this work, the interactions between the drug and clay minerals surfaces are studied at molecular level by computational methods. The optimization of the adsorption of praziquantel in sepiolite nanochannels and in the montmorillonite interlayer space has been studied by using force fields based on empirical interatomic potentials and at quantum mechanical level. The results showed the main interactions between the drug and both clay minerals surfaces at the confined spaces of these minerals, and favorable adsorption energies of the praziquantel-clays complexes were obtained. Therefore, theoretical calculations allow knowing how the drug is adsorbed in the clays and in the case of the montmorillonite how many molecules of the drug are adsorbed in the interlayer space of the mineral according to the experimental data.

Fast and Accurate Quantum Chemical Modeling of Infrared Spectra of Condensed-Phase Systems.

An efficient approach for an accurate quantum mechanical (QM) modeling of infrared (IR) spectra of condensed-phase systems is described. An ensemble of energetically low-lying cluster structures of a solute molecule surrounded by an explicit shell of solvent molecules is efficiently generated at the semiempirical tight-binding QM level and then reoptimized at the density functional theory level of theory. The IR spectrum of the solvated molecule is obtained as a thermodynamic average of harmonically computed QM spectra for all significantly populated cluster structures. The accuracy of such simulations in comparison to experimental data for some organic compounds and their solutions is shown to be the same or even better than the corresponding QM computations of the gas-phase IR spectrum for the isolated molecule.

Multistate QM/QM Extrapolation of UV/Vis Absorption Spectra with Point Charge Embedding.

The simulation of UV/vis absorption spectra of large chromophores is prohibitively expensive with accurate quantum mechanical (QM) methods. Thus, hybrid methods, which treat the core chromophoric region at a high level of theory while the substituent effects are treated with a more computationally efficient method, may provide the best compromise between cost and accuracy. The ONIOM (Our own N-layered Integrated molecular Orbital molecular Mechanics) method has proved successful at describing ground-state processes. However, for excited states, it suffers from difficulties in matching the correct excited states among the different levels of theory. We devised an approach, based on the ONIOM extrapolation formula, to combine two QM levels of theory to extrapolate entire excitation bands rather than individual states. In this contribution, we extend the same QM/QM hybrid scheme to include polarization effects on the core region through point charge embedding. The charges are computed to reproduce the electrostatic potential of the entire chromophore at the low level of theory, with proper constraints to avoid overpolarization issues at the boundary between layers. We test this approach on a variety of model compounds that show how the multistate QM/QM-embedding scheme is able to accurately reproduce the spectrum of the entire system at the high level of theory better than (i) the bare QM/QM hybrid scheme, (ii) the low-level calculation on the entire system, and (iii) the high-level calculation on the core region.

Localized Molecular Orbital-Based Embedding Scheme for Correlated Methods.

Embedding strategies currently provide the best compromise between accuracy and computational cost in modeling chemical properties and processes of large and complex systems. In this framework, different methods have been proposed all over the years, from the very popular QM/MM approaches to the more recent and very promising density matrix and density functional embedding techniques. Here, we present a further development of the quantum mechanics/extremely localized molecular orbital technique (QM/ELMO) method, a recently proposed multiscale embedding strategy in which the chemically active region of the investigated system is treated at a fully quantum mechanical level, while the rest is described by frozen extremely localized molecular orbitals previously transferred from proper libraries or tailor-made model molecules. In particular, in this work we discuss and assess in detail the extension of the QM/ELMO approach to density functional theory and post-Hartree-Fock techniques by evaluating its performances when it is used to describe chemical reactions, bond dissociations, and intermolecular interactions. The preliminary test calculations have shown that, in the investigated cases, the new embedding strategy enables the results of the corresponding fully quantum mechanical computations to be reproduced within chemical accuracy in almost all the cases but with a significantly reduced computational cost, especially when correlated post-Hartree-Fock strategies are used to describe the quantum mechanical subsystem. In light of the obtained results, we already envisage the future application of the new correlated QM/ELMO techniques to the investigation of more challenging problems, such as the modeling of enzyme catalysis, the study of excited states of biomolecules, and the refinement of macromolecular X-ray crystal structures.

Performance analysis of the perovskite solar cells by a realistic, DFT-accurate optical absorption spectrum

In all the available simulator software, the absorption spectrum is calculated by a simplified, mathematical function which provides an approximation of the real spectrum. Here, the absorption spectrum of MAPbX3 perovskites and ZnO, as absorber and electron transport layers, has been calculated with the quantum-mechanical level of accuracy by DFT method. These realistic absorption spectrums have been employed in SCAPS simulator. The results reveal significant differences between the default, analytical spectrum, and the spectrum obtained by DFT. DFT-calculated spectrum is used to study the performance of the cell as well as the effect of absorber thickness, absorber dopant concentration, and defect densities at the interface of the electron transport layer. The results show the closest agreement with the experiments and confirm the superior performance of the MAPbI3 absorber over MAPbBr3 and MAPbCl3; 2500 nm, 1015 cm−3, and 1010 cm−3 being its optimum thickness, dopant concentration, and interface defect density in the investigated cell structure, respectively.

Multiscale Molecular Modeling in G Protein-Coupled Receptor (GPCR)-Ligand Studies.

G protein-coupled receptors (GPCRs) are major drug targets due to their ability to facilitate signal transduction across cell membranes, a process that is vital for many physiological functions to occur. The development of computational technology provides modern tools that permit accurate studies of the structures and properties of large chemical systems, such as enzymes and GPCRs, at the molecular level. The advent of multiscale molecular modeling permits the implementation of multiple levels of theories on a system of interest, for instance, assigning chemically relevant regions to high quantum mechanics (QM) level of theory while treating the rest of the system using classical force field (molecular mechanics (MM) potential). Multiscale QM/MM molecular modeling have far-reaching applications in the rational design of GPCR drugs/ligands by affording precise ligand binding configurations through the consideration of conformational plasticity. This enables the identification of key binding site residues that could be targeted to manipulate GPCR function. This review will focus on recent applications of multiscale QM/MM molecular simulations in GPCR studies that could boost the efficiency of future structure-based drug design (SBDD) strategies.

Substitutional carbon defects in silicon: A quantum mechanical characterization through the infrared and Raman spectra.

The infrared (IR) and Raman spectra of eight substitutional carbon defects in silicon are computed at the quantum mechanical level by using a periodic supercell approach based on hybrid functionals, an all electron Gaussian type basis set and the CRYSTAL code. The single substitutional C s case and its combination with a vacancy (C s V and C s SiV) are considered first. The progressive saturation of the four bonds of a Si atom with C is then examined. The last set of defects consists of a chain of adjacent carbon atoms C , with i = 1-3. The simple substitutional case, C s , is the common first member of the three sets. All these defects show important, very characteristic features in their IR spectrum. One or two C related peaks dominate the spectra: at 596 cm-1 for C s (and C s SiV, the second neighbor vacancy is not shifting the C s peak), at 705 and 716 cm-1 for C s V, at 537 cm-1 for C and C (with additional peaks at 522, 655 and 689 for the latter only), at 607 and 624 cm-1 , 601 and 643 cm-1 , and 629 cm-1 for SiC , SiC , and SiC , respectively. Comparison with experiment allows to attribute many observed peaks to one of the C substitutional defects. Observed peaks above 720 cm-1 must be attributed to interstitial C or more complicated defects.

The Pauli and Lévy-Leblond equations, and the spin current density

We review the literature on the Pauli equation and its current density, discussing the progression from the original phenomenological version of Pauli to its derivation by Lévy-Leblond from a linearization of the Schrödinger equation. It was established conclusively by Lévy-Leblond’s work that the spin of a spin-1/2 particle such as an electron is non-relativistic in nature, contrary to what was often stated following Dirac’s derivation of a relativistic wave equation, and his subsequent demonstration that Pauli’s spin interaction term appeared in the non-relativistic limit. In this limit, the Gordon decomposition of the associated probability current density was found to contain a spin-dependent term. Such a term does not follow, however, from the usual derivation of the current density from the Pauli equation, although various physically motivated but otherwise ad hoc explanations were put forward to account for it. We comment on the only exception to these of which we are aware implying the spin term in the current was in fact non-relativistic in nature. However, the earlier work of Lévy-Leblond had already shown, with no additional assumptions, that this term was a prominent feature of the current density derived from his equation. Hence, just as with the spin itself, the spin current was non-relativistic, claims to the contrary notwithstanding. We present a somewhat simplified derivation of the Lévy-Leblond equation and its current density, commenting on possibilities for experimental work that might indicate measurable consequences of the spin term in the current density. The presentation is at a level of quantum mechanics, electromagnetic theory, and mathematical methods typical of courses taken by first-year graduate students in physics, assuming some familiarity with Pauli spin matrices and the Dirac equation. Calculations are presented in detail, making the material suitable for use by teachers as supplementary problems for assignments, and development of theoretical concepts peculiar to the Pauli equation and its probability current density.

Assessing the viability of silicate nanoclusters as carriers of the anomalous microwave emission: a quantum mechanical study

Nanosized silicate dust is likely to be abundant in many astronomical environments and it is a prime candidate for being the source of the anomalous microwave emission (AME). To assess the viability of silicate nanoclusters as AME carriers, their detailed properties need to be established. Using quantum chemical calculations, we compute the accurate chemical and electronic structures of three families of nanoclusters with astrophysically relevant compositions: Mg-rich olivine (Mg2SiO4)N, Mg-rich pyroxene (MgSiO3)N, and silicon monoxide (SiO)N, all in the ≤1 nm diameter size regime and for neutral and ± 1 charge states. From these fundamental data, we directly derive the shapes, ionization potentials, electron affinities, and dipole moments of all nanoclusters. The aspect ratio of the nanoclusters fluctuates significantly with N for small sizes, but especially for the olivine and pyroxene nanoclusters, it tends to stabilize towards ~1.3 for the largest sizes considered. These latter two nanocluster families tend to have mass distributions consistent with approximately prolate ellipsoidal shapes. Our calculations reveal that the dipole moment of all our nanoclusters can be substantially affected by changes in chemical structure (i.e. different isomers for a fixed N), ionisation, and substitution of Mg by Fe. Although all these factors are important, the dipole moments of our Mg-rich nanoclusters are always found to be large enough to account for the observed AME. However, (SiO)N nanoclusters are only likely to be potential AME contributors when they are both charged and their chemical structures are anisotropically segregated. We also model the emissivity per H of a representative (Mg2SiO4)3 nanocluster by directly calculating the quantum mechanical rotational energy levels and assuming a distribution of occupied levels in accordance with equilibrium Boltzmann statistics. We compare our bottom-up results with previously published classical models and show that a population of silicate nanoclusters containing only 1% of the total Si budget can reproduce the AME emissivity.

Interaction energy prediction of organic molecules using deep tensor neural network

The interaction energy of two molecules system plays a critical role in analyzing the interacting effect in molecular dynamic simulation. Since the limitation of quantum mechanics calculating resources, the interaction energy based on quantum mechanics can not be merged into molecular dynamic simulation for a long time scale. A deep learning framework, deep tensor neural network, is applied to predict the interaction energy of three organic related systems within the quantum mechanics level of accuracy. The geometric structure and atomic types of molecular conformation, as the data descriptors, are applied as the network inputs to predict the interaction energy in the system. The neural network is trained with the hierarchically generated conformations data set. The complex tensor hidden layers are simplified and trained in the optimization process. The predicted results of different molecular systems indicate that deep tensor neural network is capable to predict the interaction energy with 1 kcal/mol of the mean absolute error in a relatively short time. The prediction highly improves the efficiency of interaction energy calculation. The whole proposed framework provides new insights to introducing deep learning technology into the interaction energy calculation.

Energy-Screened Many-Body Expansion: A Practical Yet Accurate Fragmentation Method for Quantum Chemistry.

We introduce an implementation of the truncated many-body expansion, MBE(n), in which the n-body corrections are screened using the effective fragment potential force field, and only those that exceed a specified energy threshold are computed at a quantum-mechanical level of theory. This energy-screened MBE(n) approach is tested at the n = 3 level for a sequence of water clusters, (H2O)N=6-34. A threshold of 0.25 kJ/mol eliminates more than 80% of the subsystem electronic structure calculations and is even more efficacious in that respect than is distance-based screening. Even so, the energy-screened MBE(3) method is faithful to a full-system quantum chemistry calculation to within 1-2 kJ/mol/monomer, even in good quality basis sets such as aug-cc-pVTZ. These errors can be reduced by means of a two-layer approach that involves a Hartree-Fock calculation for the entire cluster. Such a correction proves to be necessary in order to obtain accurate relative energies for conformational isomers of (H2O)20, but the cost of a full-system Hartree-Fock calculation remains smaller than the cost of three-body subsystem calculations at correlated levels of theory. At the level of second-order Møller-Plesset perturbation theory (MP2), a screened MBE(3) calculation plus a full-system Hartree-Fock calculation is less expensive than a full-system MP2 calculation starting at N = 12 water molecules. This is true even if all MBE(3) subsystem calculations are performed on a single 40-core compute node, i.e., without significant parallelization. Energy-screened MBE(n) thus provides a fragment-based method that is accurate, stable in large basis sets, and low in cost, even when the latter is measured in aggregate computer time.

Synthesis of sensitive novel dual Signaling pyridopyrimidine-based fluorescent “turn off” chemosensors for anions determination

The synthesis of 2-hydroxybenzoyl pyridopyrimidines (M1-M4) has been carried out with 3-formyl chrome derivatives and 6-amino-1-methyluracil to employ them as anion chemosensors. Pyridopyrimidine-based compounds were studied as colorimetric and fluorescent receptors for anion sensing. The observations with naked eye and the data obtained by UV–visible, fluorescence and 1H NMR spectroscopy demonstrated selectivity for fluoride, acetate and cyanides among the pool of different anions. However, the spectral data involving fluoride anion showed particularly sharp and strong interactions. In sensing process, the binding of pyridopyrimidine amino (NH) and hydroxyl groups (OH) via hydrogen bonding F−····H–N/–O induced the colorimetric and “turn off” fluorescent response. The binding mode of action was further studied by 1H NMR titrations that supported gradual deprotonation mechanism. The fluoride ion detection limit was in the range of 3.51 × 10−8 M to 1.77 × 10−6 M for probes M1-M4 and were lower than the maximum permissible concentration of F− ion in drinking water (5.3 × 10−3 M) set by World Health Organization (WHO) that was found to be influenced by the nature of aromatic substituents. Theoretical study of receptor interactions with fluoride anion via O–H and N–H groups was also carried out at the quantum mechanical level.

Investigation of protein-protein interactions and hot spot region between PD-1 and PD-L1 by fragment molecular orbital method

Inhibitors to interfere protein-protein interactions (PPI) between programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) block evasion of cancers from immune surveillance. Analyzing hot spot residues in PPI is important for small-molecule drug development. In order to find out hot spots on PPI interface in PD-1/PD-L1 complex, we analyzed PPI in PD-1/PD-L1 with a new analysis method, 3-dimensional scattered pair interactions energies (3D-SPIEs), which assorts significant interactions with fragment molecular orbital (FMO) method. By additionally analyzing PPI in PD-1/antibody and PD-L1/antibody complexes, and small-ligand interactions in PD-L1/peptide and PD-L1/small-molecule complexes, we narrowed down the hot spot region with 3D-SPIEs-based interaction map, which integrates PPI and small-ligand interactions. Based on the map, there are two hot spot regions in PPI of PD-1/PD-L1 and the first hot spot region is important for inhibitors. In particular, LY56, LE58, and LN66 in the first hot spot of PD-L1 are important for PD-L1-antibodies and small-inhibitors in common, while LM115 is important for small-inhibitors. Therefore, the 3D-SPIEs-based map would provide valuable information for designing new small-molecule inhibitors to inhibit PPI of PD-1/PD-L1 and the FMO/3D-SPIEs method provides an effectual tool to understand PPI and integrate PPI and small-ligand interactions at a quantum mechanical level.

Ruthenium coordination preferences in imidazole-containing systems revealed by electrospray ionization mass spectrometry and molecular modeling: Possible cues for the surprising stability of the Ru (III)/tris (hydroxymethyl)-aminomethane/imidazole complexes.

Ruthenium is a platinoid that exhibits a range of unique chemical properties in solution, which are exploited in a variety of applications, including luminescent probes, anticancer therapies, and artificial photosynthesis. This paper focuses on a recently demonstrated ability of this metal in its +3 oxidation state to form highly stable complexes with tris (hydroxymethyl)aminomethane (H2 NC(CH2 OH)3 , Tris-base or T) and imidazole (Im) ligands, where a single RuIII cation is coordinated by two molecules of each T and Im. High-resolution electrospray ionization mass spectrometry (ESI MS) is used to characterize RuIII complexes formed by placing a RuII complex [(NH3 )5 RuII Cl]Cl in a Tris buffer under aerobic conditions. The most abundant ionic species in ESI MS represent mononuclear complexes containing an oxidized form of the metal, ie, [Xn RuIII T2 - 2H]+ , where X could be an additional T (n = 1) or NH3 (n = 0-2). Di- and tri-metal complexes also give rise to a series of abundant ions, with the highest mass ion representing a metal complex with an empirical formula Ru3 C24 O21 N6 H66 (interpreted as cyclo(T2 RuO)3 , a cyclic oxo-bridged structure, where the coordination sphere of each metal is completed by two T ligands). The empirical formulae of the binuclear species are consistent with the structures representing acyclic fragments of cyclo(T2 RuO)3 with addition of various combinations of ammonia and dioxygen as ligands. Addition of histidine in large molar excess to this solution results in complete disassembly of poly-nuclear complexes and gives rise to a variety of ionic species in the ESI mass spectrum with a general formula [RuIII Hisk Tm (NH3 )n - 2H]+ , where k = 0 to 2, m = 0 to 3, and n = 0 to 4. Ammonia adducts are present for all observed combinations of k and m, except k = m = 2, suggesting that [His2 RuIII T2 - 2H]+ represents a complex with a fully completed coordination sphere. The observed cornucopia of RuIII complexes formed in the presence of histidine is in stark contrast to the previously reported selective reactivity of imidazole, which interacts with the metal by preserving the RuT2 core and giving rise to a single abundant ruthenium complex (represented by [Im2 RuIII T2 - 2H]+ in ESI mass spectra). Surprisingly, the behavior of a hexa-histidine peptide (HHHHHH) is similar to that of a single imidazole, rather than a single histidine amino acid: The RuT2 core is preserved, with the following ionic species observed in ESI mass spectra: [HHHHHH·(RuIII T2 )m - (3m-1)H]+ (m = 1-3). The remarkable selectivity of the imidazole interaction with the RuIII T2 core is rationalized using energetic considerations at the quantum mechanical level of theory.

Fully Quantum Chemical Treatment of Chromophore-Protein Interactions in Phytochromes.

The intriguing ability of phytochromes to photoconvert between red-absorbing (Pr) and far-red-absorbing (Pfr) states depends on key interactions between a bilin chromophore and protein matrix. However, both the identification of the chemical nature and quantification of chromophore-protein interactions have not been yet fully investigated by experiments or extensive computations. Here, we presented a powerful and straightforward approach based on the fragment molecular orbital method to identify the nature and quantify the strength of the noncovalent interactions at a fully quantum mechanical level between the biliverdin (BV) chromophore and protein matrix of the Deinococcus radiodurans phytochrome (DrBphP) in the Pr state. By using pair interaction energy decomposition analysis approach, the pyrrole water, Asp207, and Glu27 were detected as key residues for the stabilization of the pyrrole rings of the BV chromophore through the formation of six H-bonds. Furthermore, the conserved Arg254 and His260 were also identified as essential residues in the conformational stability of both propionic side chains B and C. Moreover, new interactions were identified in the chromophore-binding pocket, two nonclassical H-bonds (CH/O interactions) between Asp207 and Tyr263, and an OH/π interaction between Tyr263 and ring D of the BV chromophore, which might have photochemical relevance.

Molecular Vibrational Frequencies with Multiple Quantum Protons within the Nuclear-Electronic Orbital Framework.

The nuclear-electronic orbital (NEO) approach treats all electrons and specified nuclei, typically protons, on the same quantum mechanical level. Proton vibrational excitations can be calculated using multicomponent time-dependent density functional theory (NEO-TDDFT) for fixed classical nuclei. Recently the NEO-DFT(V) approach was developed to enable the calculation of molecular vibrational frequencies for modes composed of both classical and quantum nuclei. This approach uses input from NEO-TDDFT to construct an extended NEO Hessian that depends on the expectation values of the quantum protons as well as the classical nuclear coordinates. Herein strategies are devised for extending these approaches to molecules with multiple quantum protons in a self-contained, effective, and computationally practical manner. The NEO-TDDFT method is shown to describe vibrational excitations corresponding to collective nuclear motions, such as linear combinations of proton vibrational excitations. The NEO-DFT(V) approach is shown to incorporate the most significant anharmonic effects in the molecular vibrations, particularly for the hydrogen stretching modes. These theoretical strategies pave the way for a wide range of multicomponent quantum chemistry applications.

Quantum Calculations in Solution of Energies, Structures, and Properties with a Domain Decomposition Polarizable Continuum Model.

In this work, we present the first implementation of the domain decomposition polarizable continuum model for a solute described at a quantum mechanical level of theory. After briefly recapitulating the theory, we discuss the coupling of ddPCM to a quantum mechanical level of theory based on the self-consistent field approach, i.e., Hartree-Fock, density functional theory, and semiempirical methods. We then present benchmarks of the new implementation, comparing it to a currently available state-of-the-art one, and use it to describe the structure and excitation properties of a large multichromophoric system.

A Fragmenting Protocol with Explicit Hydration for Calculation of Binding Enthalpies of Target-Ligand Complexes at a Quantum Mechanical Level.

Optimization of the enthalpy component of binding thermodynamics of drug candidates is a successful pathway of rational molecular design. However, the large size and missing hydration structure of target-ligand complexes often hinder such optimizations with quantum mechanical (QM) methods. At the same time, QM calculations are often necessitated for proper handling of electronic effects. To overcome the above problems, and help the QM design of new drugs, a protocol is introduced for atomic level determination of hydration structure and extraction of structures of target-ligand complex interfaces. The protocol is a combination of a previously published program MobyWat, an engine for assigning explicit water positions, and Fragmenter, a new tool for optimal fragmentation of protein targets. The protocol fostered a series of fast calculations of ligand binding enthalpies at the semi-empirical QM level. Ligands of diverse chemistry ranging from small aromatic compounds up to a large peptide helix of a molecular weight of 3000 targeting a leukemia protein were selected for systematic investigations. Comparison of various combinations of implicit and explicit water models demonstrated that the presence of accurately predicted explicit water molecules in the complex interface considerably improved the agreement with experimental results. A single scaling factor was derived for conversion of QM reaction heats into binding enthalpy values. The factor links molecular structure with binding thermodynamics via QM calculations. The new protocol and scaling factor will help automated optimization of binding enthalpy in future molecular design projects.

Nitrogen interstitial defects in silicon. A quantum mechanical investigation of the structural, electronic and vibrational properties

The vibrational features of eight interstitial nitrogen related defects in silicon have been investigated at the first principles quantum mechanical level by using a periodic supercell approach, a hybrid functionals, an all electron Gaussian type basis set and the Crystal code. The list includes defects that will be indicated as Ni (one N atom forming a bridge between two Si atoms), Ni-Ns (one interstitial and one substitutional N atom linked to the same Si atom), Ni-Ni (two Ni defects linked to the same couple of silicon atoms) and Ni-Sii-Ni (two Ni defects linked to the same interstitial silicon atom). Four 〈0 0 1〉 split interstitial (dumbbell) defects have also been considered, in which one lattice atom splits in two, and as a result the two interstitial atoms are three fold coordinated: they are two N (indicated as IN-N), one N and one Si (IN-Si), one N and one C (IC-N). For comparison, also the case with two Si atoms (ISi-Si) has been included. Four of these eight defects have unpaired electrons, and have been described through the UHF (Unrestricted Hartree-Fock like) computational scheme. The local defect geometry and the charge and spin density distributions have been analyzed. For the first time, intensities of IR and Raman spectra were calculated along with the frequencies, and this is crucial for the comparison of theoretical simulations with experiments. All these defects present very characteristic features in their IR spectrum, dominated by one or two very intense peaks. It has been possible to find a simulated counterpart to each one of the five peaks reported by Stein in 1985 (Applied Physics Letters, 47, 1339), and then to establish a correspondence between the microscopic structure of the defects and the IR intense peaks. The Raman spectra are in all cases dominated by the perfect silicon peak at about 530 cm−1, and are then not very useful for the characterization of the defects.

Analysis of Density Functional Tight Binding with Natural Bonding Orbitals.

The description of chemical bonding by the density functional tight binding (DFTB) model is analyzed using natural bonding orbitals (NBOs) and compared to results from density functional theory (B3LYP/aug-cc-pVTZ) calculations. Several molecular systems have been chosen to represent fairly diverse bonding scenarios that include standard covalent bonds, hypervalent interactions, multicenter bonds, metal-ligand interactions (with and without the pseudo-Jahn-Teller effect), and through-space donor-acceptor interactions. Overall, the results suggest that DFTB3/3OB provides physically sound descriptions for the different bonding scenarios analyzed here, as reflected by the general agreement between DFTB3 and B3LYP NBO properties, such as the nature of the NBOs, the magnitudes of natural charges and bond orders, and the dominant donor-acceptor interactions. The degree of ligand-to-metal charge transfer and the ionic nature of pentavalent phosphate are overestimated, likely reflecting the minimal-basis nature of DFTB3/3OB. Moreover, certain orbital interactions, such as geminal interactions, are observed to be grossly overestimated by DFTB3 for hypervalent phosphate and several transition metal compounds that involve copper and nickel. The study indicates that results from NBO analysis can be instructive for identifying electronic structure descriptions at the approximate quantum-mechanical level that require improvement and thus for guiding the systematic improvement of these methods.