Local Ionization Energy Research Articles

The average local ionization energy as a tool for identifying reactive sites on defect-containing model graphene systems

In a continuing effort to further explore the use of the average local ionization energy [Formula: see text] as a computational tool, we have investigated how well [Formula: see text] computed on molecular surfaces serves as a predictive tool for identifying the sites of the more reactive electrons in several nonplanar defect-containing model graphene systems, each containing one or more pentagons. They include corannulene (C20H10), two inverse Stone-Thrower-Wales defect-containing structures C26H12 and C42H16, and a nanotube cap model C22H6, whose end is formed by three fused pentagons. Coronene (C24H12) has been included as a reference planar defect-free graphene model. We have optimized the structures of these systems as well as several monohydrogenated derivatives at the B3PW91/6-31G* level, and have computed their I(r) on molecular surfaces corresponding to the 0.001 au, 0.003 au and 0.005 au contours of the electronic density. We find that (1) the convex sides of the interior carbons of the nonplanar models are more reactive than the concave sides, and (2) the magnitudes of the lowest I(r) surface minima (the I S, min) correlate well with the interaction energies for hydrogenation at these sites. These I S, min values decrease in magnitude as the nonplanarity of the site increases, consistent with earlier studies. A practical benefit of the use of I(r) is that a single calculation suffices to characterize the numerous sites on a large molecular system, such as graphene and defect-containing graphene models.

Surface Reactivity for Chlorination on Chlorinated (5,5) Armchair SWCNT: A Computational Approach

In the present work, we first attached one chlorine radical and then examined the site selectivity for the addition of a second chlorine radical on the external surface of (5,5) armchair single-walled carbon nanotubes (SWCNTs) of 9 and 15 carbon layers. Optimized geometries and energetics were determined using density functional theory (DFT), at the M06-2X/6-31G(d,p) level. Computed reaction energy values for second chlorination have been used to corroborate the prediction of the reactivities of different sites based on the electron density distribution in the singly occupied molecular orbital (SOMO), total spin density, the DFT based local reactivity descriptors (viz., Fukui function, local softness), and the average local ionization energy. Natural bond orbital (NBO) analysis was performed to confirm the covalent bonding between the chlorine and carbon of the SWCNT. The present study reveals that the first chlorine attached to the SWCNT behaves like an ortho- and para-director. The addition of a second chlorine on an already chlorinated SWCNT exhibits positional preference.

Aromatic Residues Regulating Electron Relay Ability of S-Containing Amino Acids by Formations of S∴π Multicenter Three-Electron Bonds in Proteins

The ab initio calculations predict that the side chains of four aromatic amino acids (Phe, His, Tyr, and Trp residues) may promote methionine and cystine residues to participate in the protein electron hole transport by the formation of special multicenter, three-electron bonds (S∴π) between the S-atoms and the aromatic rings. The formations of S∴π bonds can efficiently lower the local ionization energies, which drive the electron hole moving to the close side chains of S-containing and aromatic residues in proteins. Additionally, the proper binding energies for the S∴π bonds imply that the self-movement of proteins can dissociate these three-electron bonds and promote electron hole relay.

3D-QSAR Based on Quantum-Chemical Molecular Fields: Toward an Improved Description of Halogen Interactions

Current 3D-QSAR methods such as CoMFA or CoMSIA make use of classical force-field approaches for calculating molecular fields. Thus, they can not adequately account for noncovalent interactions involving halogen atoms like halogen bonds or halogen-π interactions. These deficiencies in the underlying force fields result from the lack of treatment of the anisotropy of the electron density distribution of those atoms, known as the "σ-hole", although recent developments have begun to take specific interactions such as halogen bonding into account. We have now replaced classical force field derived molecular fields by local properties such as the local ionization energy, local electron affinity, or local polarizability, calculated using quantum-mechanical (QM) techniques that do not suffer from the above limitation for 3D-QSAR. We first investigate the characteristics of QM-based local property fields to show that they are suitable for statistical analyses after suitable pretreatment. We then analyze these property fields with partial least-squares (PLS) regression to predict biological affinities of two data sets comprising factor Xa and GABA-A/benzodiazepine receptor ligands. While the resulting models perform equally well or even slightly better in terms of consistency and predictivity than the classical CoMFA fields, the most important aspect of these augmented field-types is that the chemical interpretation of resulting QM-based property field models reveals unique SAR trends driven by electrostatic and polarizability effects, which cannot be extracted directly from CoMFA electrostatic maps. Within the factor Xa set, the interaction of chlorine and bromine atoms with a tyrosine side chain in the protease S1 pocket are correctly predicted. Within the GABA-A/benzodiazepine ligand data set, PLS models of high predictivity resulted for our QM-based property fields, providing novel insights into key features of the SAR for two receptor subtypes and cross-receptor selectivity of the ligands. The detailed interpretation of regression models derived using improved QM-derived property fields thus provides a significant advantage by revealing chemically meaningful correlations with biological activity and helps in understanding novel structure-activity relationship features. This will allow such knowledge to be used to design novel molecules on the basis of interactions additional to steric and hydrogen-bonding features.

Hydrogenation and Fluorination of Graphene Models: Analysis via the Average Local Ionization Energy

We have investigated the use of the average local ionization energy, I[combining overline](S)(r), as a means for rapidly predicting the relative reactivities of different sites on two model graphene surfaces toward the successive addition of one, two, and three hydrogen or fluorine atoms. The I[combining overline](S)(r) results were compared with directly computed interaction energies, at the B3LYP/6-311G(d,p) level. I[combining overline](S)(r) correctly predicts that the edges of graphene sheets are more reactive than the interior portions. It shows that added hydrogens activate the adjoining (ortho) sites and deactivate those that are separated by one site (meta). Overall, I[combining overline](S)(r) is effective for rapidly (single calculations) estimating the relative site reactivities of these large systems, although it reflects only the system prior to an interaction and cannot take into account postinteraction factors, e.g., structural distortion.

Quantitative analysis of molecular surface based on improved Marching Tetrahedra algorithm

Quantitative analysis of molecular surface is a valuable technique for analyzing non-covalent interaction, studying molecular recognition mode, predicting reactive site and reactivity. An efficient way to realize the analysis was first proposed by Bulat et al. (J. Mol. Model., 16, 1679), in which Marching Tetrahedra (MT) approach commonly used in computer graphics is employed to generate vertices on molecular surface. However, it has been found that the computations of the electrostatic potential in the MT vertices are very expensive and some artificial surface extremes will be presented due to the uneven distribution of MT vertices. In this article, we propose a simple and reliable method to eliminate these unreasonably distributed surface vertices generated in the original MT. This treatment can save more than 60% of total analysis time of electrostatic potential, yet the loss in accuracy is almost negligible. The artificial surface extremes are also largely avoided as a byproduct of this algorithm. In addition, the bisection iteration procedure has been exploited to improve accuracy of linear interpolation in MT. The most appropriate grid spacing for surface analysis has also been investigated. 0.25 and 0.20bohr are recommended to be used for surface analysis of electrostatic potential and average local ionization energy, respectively.

Predicting the Sites and Energies of Noncovalent Intermolecular Interactions Using Local Properties

Feed-forward artificial neural nets have been used to recognize H-bond donor and acceptor sites on drug-like molecules based on local properties (electron density, molecular electrostatic potential and local ionization energy, electron affinity, and polarizability) calculated at grid points around the molecule. Interaction energies for training were obtained from B97-D and ωB97X-D/aug-cc-pVDZ density-functional theory calculations on a series of model central molecules and H-bond acceptor and donor probes constrained to the grid points used for training. The resulting models provide maps of both classical and unusual H- and halogen-bonding sites. Note that these reactions result even though only classical H-bond donors and acceptors were used as probes around the central molecules. Some examples demonstrate the ability of the models to take the electronics of the central molecule into consideration and to provide semiquantitative estimates of interaction energies at low computational cost.

Investigation of retention behavior of polychlorinated biphenyl congeners on 18 different HRGC columns using molecular surface average local ionization energy descriptors

In this paper, based on the general interaction properties function (GIPF) family descriptors computed at the B3LYP/6-31G* level in Gaussian98 software, a significant quantitative structure–retention relationship (QSRR) models for the high resolution gas chromatographic relative retention time (HRGC-RRT) of all PCB congeners on 18 different HRGC capillary columns were constructed by using multiple linear regression (MLR) analysis, following the guidelines for development and validation of QSRR models. By means of the elimination selection stepwise regression algorithms, the molecular surface average local ionization energy was selected as one-parameter univariate linear regression to develop a QSRR model for prediction of GC-RRT of PCBs on each stationary phase. The accuracy of all developed models was confirmed using different types of internal and external procedures. A successful interpretation of the complex relationship between HRGC-RRTs of PCBs and the chemical structures was achieved by QSRR.

Halogen bonding and beyond: factors influencing the nature of CN–R and SiN–R complexes with F–Cl and Cl2

It was recently shown that complexes of the type F–Cl···CN–R, ostensibly halogen bonded, sometimes have properties (relatively high binding energies, short Cl–C separations and considerably lengthened F–Cl distances) that are inconsistent with typical halogen bonds (Del Bene et al. in J Phys Chem A 114:12958–12962, 2010). We attribute these anomalous features, as well as analogous observations for F–Cl···SiN–R systems, to the strong polarization of the CN–R carbons and SiN–R silicons by the electric field of the positive σ-hole of the F–Cl chlorine. This polarization may evolve into some degree of dative sharing of electrons by the carbons and silicons. This interpretation is supported by the fact that complexes of CN–R and SiN–R with Cl–Cl, which has a much weaker positive σ-hole than F–Cl, are considerably less likely to show the unusual features. It is demonstrated that the full ranges of binding energies of the CN–R and SiN–R complexes with either F–Cl or Cl–Cl can be represented well (R 2 > 0.96) in terms of the most negative electrostatic potentials and the lowest local ionization energies on the carbon and silicon surfaces. These properties reflect the electrostatic components of the interactions and the polarizabilities/dative reactivities of the carbons and silicons.

Study on Radial Position of Impurity Ions in Core and Edge Plasma of LHD Using Space-Resolved EUV Spectrometer

Radial profiles of impurity ions of carbon, neon and iron were measured for high-temperature plasmas in large helical device (LHD) using a space-resolved extreme ultraviolet (EUV) spectrometer in the wavelength range of 60 Å to 400 Å. The radial positions of the impurity ions obtained are compared with the local ionization energies, Ei of these impurity ions and the electron temperatures TeZ there. The impurity ions with 0.3 keV ≤ Ei ≤ 1.0 keV are always located in outer region of plasma, i.e., 0.7 ≤ ρ ≤ 1.0, and those with Ei ≤ 0.3 keV are located in the ergodic layer, i.e., 1.0 ≤ ρ ≤ 1.1, with a sharp peak edge, where ρ is the normalized radial position. It is newly found that TeZ is approximately equal to Ei for the impurity ions with Ei ≤ 0.3 keV, whereas roughly half the value of Ei for the impurity ions with 0.3 keV ≤ Ei ≤ 1.0 keV. It is known that TeZ is considerably lower than Ei in the plasma edge and approaches to Ei in the plasma core. Therefore, this result seems to originate from the difference in the transverse transport between the plasma edge at ρ ≤ 1.0 and the ergodic layer at ρ ≥ 1.0. The transverse transport is studied with an impurity transport simulation code. The result revealed that the difference appearing in the impurity radial positions can be qualitatively explained by the different values of diffusion coefficient, e.g., D= 0.2 m2/s and 1.0 m2/s, which can be taken as a typical index of the transverse transport.

Simulation of the Incomplete Ionization of the <i>n</i>-Type Dopant Phosphorus in 4H-SiC, Including Screening by Free Carriers

The simulation of the incomplete ionization of substitutional dopants in Silicon Carbide (SiC) is often performed using Boltzmann statistics and ionization energy values that do not depend on free carrier concentrations. But in the case of heavy doping Fermi-Dirac statistics is needed, while the case of an inhomogeneous dopants distribution or that of an excess carrier injection requires local free carrier concentration-dependent impurity ionization energies. Here a model for describing partial ionization from diluted to high homogeneous doping densities in SiC and in thermal equilibrium is presented and compared with results on Phosphorus doped 4H-SiC.

Average Local Ionization Energies as a Route to Intrinsic Atomic Electronegativities

Historically, two important approaches to the concept of electronegativity have been in terms of: (a) an atom in a molecule (e.g., Pauling) and (b) the chemical potential. An approximate form of the latter is now widely used for this purpose, although it includes a number of deviations from chemical experience. More recently, Allen introduced an atomic electronegativity scale based upon the spectroscopic average ionization energies of the valence electrons. This has gained considerable acceptance. However it does not take into account the interpenetration of valence and low-lying subshells, and it also involves some ambiguity in enumerating d valence electrons. In this paper, we analyze and characterize a formulation of relative atomic electronegativities that is conceptually the same as Allen's but avoids the aforementioned problems. It involves the property known as the average local ionization energy, I̅(r), defined as [Formula: see text], where ρi(r) is the electronic density of the i(th) orbital, having energy εi, and ρ(r) is the total electronic density. I̅(r) is interpreted as the average energy required to remove an electron at the point r. When I̅(r) is averaged over the outer surfaces of atoms, taken to be the 0.001 au contours of their electronic densities, a chemically meaningful scale of relative atomic electronegativities is obtained. Since the summation giving I̅(r) is over all occupied orbitals, the issues of subshell interpenetration and enumeration of valence electrons do not arise. The procedure is purely computational, and all of the atoms are treated in the same straightforward manner. The results of several different Hartree-Fock and density functional methods are compared and evaluated; those produced by the Perdew-Burke-Ernzerhof functional are chemically the most realistic.

ChemInform Abstract: A Computational Analysis of the Structural Features and Reactive Behavior of Some Heterocyclic Aromatic N-Oxides

Abstract An ab initio self-consistent-field molecular orbital analysis of the structural features and reactive behavior of pyridine, pyrazine and some of their N -oxide and nitro derivatives has been carried out. Optimized structures have been computed at the 6-31G ∗ level, yielding geometries in good agreement with experiment. These structures have been used to compute STO-5G electrostatic potentials and average local ionization energies on the respective molecular surfaces. There is considerable conjugation between the N -oxide groups and the aromatic rings, leading to significant para -quinonoid influence, manifested both in terms of structures and reactive properties. The charge-donor role of the N -oxide group allows the aromatic ring in pyridine N -oxide to be susceptible to electrophiles (at the para position) as well as nucleophiles; however, the rings in the pyrazine oxides are only receptive to the latter. The local ionization energies have permitted predictions of pK a values for pyrazine N -oxide and p -nitropyridine.

Validation of a Computational Model for Predicting the Site for Electrophilic Substitution in Aromatic Systems

We have investigated the scope and limitations of a method for predicting the regioisomer distribution in electrophilic aromatic substitution reactions that are under kinetic control. This method is based on calculation of the relative stabilities of the sigma-complex intermediates using density functional theory. Predictions from this method can be used quantitatively for halogenations; it agreed to an accuracy of about 1 kcal/mol with experimental observations in 10 of the 11 investigated halogenation reactions. For nitrations, the method gave useful predictions for heterocyclic substrates. The method failed for nitration of monosubstituted benzenes, and we expect that more elaborate model systems, including explicit solvent molecules, will be necessary to obtain quantitatively useful predictions for such cases. For Lewis acid promoted Friedel-Crafts acylations, the method can be expected to give qualitatively correct predictions, that is, to point out the dominating isomer. For substrates where the regioisomeric outcome is highly dependent on the reaction conditions, the method can only be of qualitative use if the concentration of the free Lewis acid is high during the reaction. We have also compared the predictive capacity of the method to that of a modern reactivity index, the average local ionization energy, I(r). The latter method is found to predict the regisolectivity in halogenations and nitrations qualitatively correctly if the positions for the I(r) minima (I(S,min)) are not too sterically hindered but fails for qualitative predictions of F-C reactions. The downscaled I(S,min) values also perform well for the quantitative prediction of regioisomer distributions of halogenations. The accuracy is slightly lower than that for the new method.

Average local ionization energy: A review

The average local ionization energy I(r) is the energy necessary to remove an electron from the point r in the space of a system. Its lowest values reveal the locations of the least tightly-held electrons, and thus the favored sites for reaction with electrophiles or radicals. In this paper, we review the definition of I(r) and some of its key properties. Apart from its relevance to reactive behavior, I(r) has an important role in several fundamental areas, including atomic shell structure, electronegativity and local polarizability and hardness. All of these aspects of I(r) are discussed.

Quantitative analysis of molecular surfaces: areas, volumes, electrostatic potentials and average local ionization energies

We describe a procedure for performing quantitative analyses of fields f(r) on molecular surfaces, including statistical quantities and locating and evaluating their local extrema. Our approach avoids the need for explicit mathematical representation of the surface and can be implemented easily in existing graphical software, as it is based on the very popular representation of a surface as collection of polygons. We discuss applications involving the volumes, surface areas and molecular surface electrostatic potentials, and local ionization energies of a group of 11 molecules.

Reactivities of Sites on (5,5) Single-Walled Carbon Nanotubes with and without a Stone-Wales Defect

The reactivities of various carbon sites on (5,5) single-walled carbon nanotubes (SWCNT) of C70H20 with and without a Stone-Wales defect have been predicted computationally. The properties determined include the average local ionization energy Is(r) and pyramidalization angle θP on the surfaces of the bare tubes, the chemisorption energies, bond lengths, stretching frequencies for chemisorbed H and F atoms, and the effects of H and F chemisorption upon the HOMO−LUMO energy gaps. There is a good correlation between the minima of the local ionization energy and the chemisorption energies at different carbon sites, indicating that Is(r) provides an effective means for rapidly and inexpensively assessing the relative reactivities of the carbon sites of SWCNTs. The pyramidalization angle (θP), which is a measure of local curvature, also shows a relationship to site reactivity. The most reactive carbon site, identified by having the lowest Is(r) and largest θP, is in the Stone-Wales defect region, which also...

A Surface-Integral Model for Log POW

Log P(OW), the negative logarithm of the octanol-water partition coefficient, is omnipresent in computational drug design. Here, we present a surface-integral model for calculating log P(OW). The model is based on local properties calculated using AM1 semiempirical molecular orbital theory. These are the molecular electrostatic potential (MEP), local ionization energy (IE(L)), local electron affinity (EA(L)), local hardness (HARD), local polarizability (POL), and the local field normal to the surface (FN). We have developed a new scheme to calculate a local hydrophobicity based on binning the range of local surface properties instead of using polynomial expansions of the base terms. The model has been trained using approximately 9500 compounds available from the literature. It was validated on approximately 1350 compounds from the literature and an in-house validation set of 768 compounds from Boehringer-Ingelheim. The model performs similarly to or slightly better than the best commercially available models. We also introduce a model based purely on conformationally rigid compounds that performs well for flexible compounds if the Boltzmann weighted predictions for the different conformers are used. This is the first 3D QSPR model based on such a large databasis that is able to benefit from using conformational ensembles.

Synthesis of novel annelated systems based on the interaction and reactivity estimation of amino‐1,5‐benzodiazepin‐2‐ones with dimethyl‐2‐oxoglutaconate

Abstract magnified image A number of substituted tetracyclic 4H‐[1,4]diazepino[3,2,1‐hi]pyrido[4,3,2‐cd]indole and tricyclic 1H‐[1,4]diazepino[2,3‐g] or [2,3‐h]quinoline derivatives were prepared from 7‐ (or 8, or 9)amino‐1,5‐benzodiazepin‐2‐ones by the Doebner–von Miller quinoline synthesis. The structure of the cyclized products depends on the position of the primary amino group and on the substituents of the diazepine ring of the starting compounds. The regiochemical outcome of the reaction was estimated by calculating average local ionization energies on the molecular surface at the Density Functional Theory (DFT) level of theory. J. Heterocyclic Chem., (2009).

A theoretical approach to the nucleophilic behavior of benzofused thieno[3,2-b]furans using DFT and HF based reactivity descriptors

Calculations of traditional HF and DFT based reactivity descriptors are reported for the isomeric benzofused thieno[3,2-b]furans in order to get insight into the factors determining the nature of their interactions with electrophiles. Global reactivity descriptors such as ionization energy, molecular hardness, electrophilicity, frontier molecular orbital energies and shapes, the condensed Fukui functions, total energies were determined and used to identify the differences in the stability and reactivity of benzofused thieno[3,2-b]furans. Additionally the bond order uniformity analysis, local ionization energy and electrostatic potential energy surfaces revealed structural differences of isomeric thieno[3,2-b]furans. Calculated values lead to the conclusion that heterocyclic system in thieno[3,2-b]benzofuran is more aromatic and stable than in isomeric benzothieno[3,2-b]furan. Theoretical results are in complete agreement with the experimental results and show exceptional reactivity of C(2) atom for both isomers.