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We present a combined experimental and theoretical study of the nature of the proposed metal-metal bonding in the tetranuclear cluster Ni4(NPtBu3)4, which features four nickel(I) centers engaged in strong ferromagnetic coupling. High-resolution single-crystal synchrotron X-ray diffraction data collected at 25 K provide an accurate geometrical structure and a multipole model electron density description. Topological analysis of the electron density in the Ni4N4 core using the quantum theory of atoms in molecules clearly identifies the bonding as an eight-membered ring of type [Ni-N-]4 without direct Ni-Ni bonding, and this result is generally corroborated by an analysis of the energy density distribution. In contrast, the calculated bond delocalization index of ∼0.6 between neighboring Ni atoms is larger than what has been found for other bridged metal-metal bonds and implies direct Ni-Ni bonding. Similar support for the presence of direct Ni-Ni bonding is found in the interacting quantum atom approach, an energy decomposition scheme, which suggests the presence of stabilizing Ni-Ni bonding interactions with an exchange-correlation energy contribution approximately 50% of that of the Ni-N interactions. Altogether, while the direct interactions between neighboring Ni centers are too weak and sterically constrained to bear the signature of a topological bond critical point, other continuous measures clearly indicate significant Ni-Ni bonding. These metal-metal bonding interactions likely mediate direct ferromagnetic exchange, giving rise to the high-spin ground state of the molecule.

The charge density distribution in a novel cocrystal (1) complex of 1,3-dimethylxanthine (theophylline) and propanedioic acid (malonic acid) has been determined. The molecules crystallize in the triclinic, centrosymmetric space group P1̅, with four independent molecules (Z = 4) in the asymmetric unit (two molecules each of theophylline and malonic acid). Theophylline has a notably high hygroscopic nature, and numerous cocrystals have shown a significant improvement in stability to humidity. A charge density study of the novel polymorph has identified interesting theoretical results correlating the stability enhancement of theophylline via cocrystallization. Topological analysis of the electron density highlighted key differences (up to 17.8) in Laplacian (∇2ρ) between the experimental (EXP) and single-point (SP) models, mainly around intermolecular-bonded carbonyls. Further investigation via molecular electrostatic potential maps reaffirmed that the charge redistribution enhanced intramolecular hydrogen bonding, predominantly for N(2′) and N(2) (61.2 and 61.8 kJ mol–1, respectively). An overall weaker lattice energy of the triclinic form (−126.1 kJ mol–1) compared to that of the monoclinic form (−133.8 kJ mol–1) suggests a lower energy threshold to overcome to initiate dissociation. Future work via physical testing of the novel cocrystal in both dissolution and solubility will further solidify the correlation between theoretical and experimental results.

We report the accelerated molecular dynamics (aMD) simulation of amyloid-β (Aβ) peptides of four different lengths (16, 28, 40, and 42 residues) and their complexes when bound to Cu(II), Fe(II), or Zn(II). 600 ns equilibrated trajectory data were analyzed for each structure from three independent 200 ns aMD simulations, generating 16 aMD trajectories. We show that the presence of a metal ion leads to reduced size and decreased mobility relative to the free peptide due to the anchoring effect of the ions. The reduced mobility was shown largely to be due to the restricted movement in N-terminal residues, most notably Asp1 and His6 that are involved in the metal-ion coordination in all cases. Significant disruption of the secondary structure and patterns of salt bridge interactions arise on the coordination of metal ions. In this regard, similarities were noted between results for Zn(II) and Fe(II), whereas results for Cu(II) are more comparable to that of the free peptides. Reweighting of free energy surfaces was carried out from aMD data to identify the properties and descriptions of local minima structures.

We report the formation of dinuclear complexes from, and photochemical oxidation of, (CH3)3-Pt(IV)(N^N) (N^N = 1,2-diimine derivatives) complexes of thiophenolate ligands to the analogous sulfinates (CH3)3Pt(N^N)(SO2Ph) and structural, spectroscopic, and theoretical studies of the latter revealing tunable photophysics depending upon the 1,2-diimine ligands. Electron-rich thiolate and conjugated 1,2-diimines encourage formation of thiolate-bridged dinuclear complexes; smaller 1,2-diimines or electron-poor thiolates favor mononuclear complexes. Photooxidation of the thiolate ligand yields hitherto unreported Pt(IV)-SO2R complexes, promoted by electron-deficient thiolates such as 4-nitrothiophenol, which exclusively forms the sulfinate complex. Such complexes exhibit expected absorptions due to π-π* ligand transitions of the 1,2-diimines mixed with spin-allowed singlet MLCT (d-π*) at relatively high energy (270–290 nm), as well as unexpected broad, lower energy absorptions between 360 and 490 nm. DFT data indicate that these low energy absorption bands result from excitation of Pt–S and Pt–C σ-bonding electrons to π* orbitals on sulfinate and 1,2-diimine, the latter of which gives rise to emission in the visible range.

UV-induced photochemical transformations of the paramagnetic [Cr(CO)4(Ph2PCH2CH2CH2PPh2)]+ complex (abbreviated [Cr(CO)4(dppp)]+) in dichloromethane was investigated by CW EPR spectroscopy. Room-temperature UV irradiation results in the rapid transformation of [Cr(CO)4(dppp)]+ into trans-[Cr(CO)2(dppp)2]+. However, low-temperature (77-120 K) UV irradiation reveals the presence of an intermediate mer-[Cr(CO)3(κ1-dppp)(κ2-dppp)]+ complex which photochemically transforms into trans-[Cr(CO)2(dppp)2]+. The derived spin Hamiltonian parameters for these complexes were confirmed by DFT calculations. The photoinduced reaction is shown to be concentration-dependent, leading to a distribution of the three complexes ([Cr(CO)4(dppp)]+, mer-[Cr(CO)3(κ1-dppp)(κ 2-dppp)]+, and trans-[Cr(CO)2(dppp)2]+). A bimolecular photoinduced mechanism is proposed to account for the formation of mer-[Cr(CO)3(κ1-dppp)(κ2-dppp)]+ and trans-[Cr(CO)2(dppp)2]+.

A series of six new Au(III) coordination compounds with phenanthroline ligands have been synthesized and studied for the inhibition of the water and glycerol channel aquaporin-3 (AQP3). From a combination of different experimental and computational approaches, further insights into the mechanisms of AQP3 inhibition by gold compounds at a molecular level have been gained. The results evidence the importance of noncoordinative adduct formation, prior to “covalent” protein binding, to achieve selective AQP3 inhibition.

A series of complexes [Et4N][Ln(NCS)4(H2O)4] (Ln = Pr, Tb, Dy, Ho, Yb) have been structurally characterized, all showing the same structure, namely a distorted square antiprismatic coordination geometry, and the Ln–O and Ln–N bond lengths following the expected lanthanide contraction. When the counterion is Cs+, a different structural motif is observed and the eight-coordinate complex Cs5[Nd(NCS)8] isolated. The thorium compounds [Me4N]4[Th(NCS)7(NO3)] and [Me4N]4[Th(NCS)6(NO3)2] have been characterized, and high coordination numbers are also observed. Finally, attempts to synthesize a U(III) thiocyanate compound has been unsuccessful; from the reaction mixture, a heterocycle formed by condensation of five MeCN solvent molecules, possibly promoted by U(III), was isolated and structurally characterized. To rationalize the inability to isolate U(III) thiocyanate compounds, thin-layer cyclic voltammetry and IR spectroelectrochemistry have been utilized to explore the cathodic behavior of [Et4N]4[U(NCS)8] and [Et4N][U(NCS)5(bipy)2] along with a related uranyl compound [Et4N]3[UO2(NCS)5]. In all examples, the reduction triggers a rapid dissociation of [NCS]− ions and decomposition. Interestingly, the oxidation chemistry of [Et4N]3[UO2(NCS)5] in the presence of bipy gives the U(IV) compound [Et4N]4[U(NCS)8], an unusual example of a ligand-based oxidation triggering a metal-based reduction. The experimental results have been augmented by a computational investigation, concluding that the U(III)–NCS bond is more ionic than the U(IV)–NCS bond.

A series of R2Sn (R = Me, Ph) complexes of the Schiff’s base salicylaldehyde acyldihydrazone with a methylene spacer of variable length have been structurally characterized in order to explore the prevalence of Sn···O noncovalent interactions. Structural studies show that these can exist, with the shortest Sn···O distance of 3.480(2) A in this library of compounds, significantly shorter than the sum of the van der Waals radii (3.92 A). Crystallographic studies also show that steric effects are important, and these interactions are seen only for compounds with Me2Sn while they are not observed for Ph2Sn. However, this is not simply a steric effect, and C–H···O interactions can compete with these Sn···O interactions. A computational study, in combination with the quantum theory of atoms in molecules, shows that these interactions are mostly electrostatic in origin with little evidence of covalency.

The solid-state structures of CF3(CF2)5CH2CO2H and a fluorous triazole are reported, both of which display a wide variety and large number of noncovalent interactions in their packing. The solid-state structure of CF3(CF2)5CH2CO2H is stabilized by multiple F···F contacts but only one C–H···F–C interaction, as well as O–H···O and C–H···O hydrogen bonds. In contrast to other reported structures, the torsion angles in the fluorous chain are close to 180°, which means that the fluorine atoms are eclipsed. A DFT study of the interactions in both compounds show that F···F interactions, along with stacking and C–H···F and C–H···O contacts, are individually weakly energetically stabilizing, but collectively, they can give rise to interaction energies of up to 13 kcal mol–1. A topological approach to the interactions using atoms-in-molecules (AIM) theory reveals that there are bond critical points between the C–F···F–C interactions as well as C–F···H–C interactions that are not recognized when using only the van d...

Molecular mechanical (MM) force fields are commonly employed for biomolecular simulations. Despite their success, the nonpolarizable nature of contemporary additive force fields limits their performance, especially in long simulations and when strong polarization effects are present. Guanine quadruplex D(R)NA molecules have been successfully studied by MM simulations in the past. However, the G-stems are stabilized by a chain of monovalent cations that create sizable polarization effects. Indeed, simulation studies revealed several problems that have been tentatively attributed to the lack of polarization. Here, we provide a detailed comparison between quantum chemical (QM) DFT-D3 and MM potential energy surfaces of ion binding to G-stems and assess differences that may affect MM simulations. We suggest that MM describes binding of a single ion to the G-stem rather well. However, polarization effects become very significant when a second ion is present. We suggest that the MM approximation substantially limits accuracy of description of energy and dynamics of multiple ions inside the G-stems and binding of ions at the stem-loop junctions. The difference between QM and MM descriptions is also explored using symmetry-adapted perturbation theory and quantum theory of atoms in molecules analyses, which reveal a delicate balance of electrostatic and induction effects.

Zirconium and hafnium metallocene dihalides based on simple polyphenyl cyclopentadienes are stable room-temperature lumophores with large Stokes shifts, emitting from states with substantial LMCT character. Their synthesis is described, including by a rapid solvent-free approach compatible with the lifetime of PET-active isotopes (89Zr). Preliminary experiments indicate the viability of these species as lumophores for fluorescence cell-imaging microscopy.

Anion-π interactions are attractive interactions between electron-poor aromatic rings and electron-rich negative ions or groups. Predicted by theoretical studies in the late 1990s, the first experimental evidence of anion-π interactions was provided by two independent studies in 2004. Since then, the role of these interactions in chemical and in biochemical systems has been investigated. In this work we report benchmark interaction energies, estimated from the extrapolated MP2 basis set limit with CCSD(T) correction, for several model complexes. These are then used to assess faster, more approximate methods including MP2 and its local approximation, along with various forms of Density Functional Theory (DFT). The most promising of these are then used to describe the geometries and interaction energies of a series of complexes between electron-poor substituted benzene rings and anions as well as examples of such interactions in models of proteins.

The interaction of triethylaluminum (TEA) with a solution of the paramagnetic Cr(I) bis(phosphine) complex [Cr(CO)41][Al(OC(CF3)3)4] (1 = Ph2PN(iPr)PPh2) has been studied using EPR and DFT. It was found that the TEA is responsible for the complete removal of all CO groups from the [Cr(CO)41]+ complex, producing the [Cr(1-bis-η6-arene)]+, and this reaction occurs via a dominant pathway involving a series of [Cr(CO)x1]+ (x < 4) intermediates, consistently including the cis-[Cr(CO)31]+ complex (species A) and the “piano-stool”-type [Cr(CO)21]+ complex (species C). A further [Cr(CO)21]+ intermediate complex (labeled species D, which is a structural isomer of species C) was also identified experimentally, suggesting a second pathway for TEA activation may also be operative. All of these paramagnetic complexes have been characterized by CW EPR, and the spin Hamiltonian parameters were verified using DFT. The distribution and type of [Cr(CO)x1]+ intermediates formed were found to be very sensitive to the experimental conditions, including the quantity and manner of TEA addition, the temperature of activation, and the aging time of the solution.

Although the encouraging antitumor activity of [PtCl2(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing isomeric 1R,2R-DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemo-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with ds-DNA, investigated by a biosensor assay and by QM/MM geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase.

For many years, MP2 served as the principal method for the treatment of noncovalent interactions. Until recently, this was the only technique that could be used to produce reasonably accurate binding energies, with binding energy errors generally below ~35%, at a reasonable computational cost. The past decade has seen the development of many new methods with improved performance for noncovalent interactions, several of which are based on MP2. Here, we assess the performance of MP2, LMP2, MP2-F12, and LMP2-F12, as well as spin component scaled variants (SCS) of these methods, in terms of their abilities to produce accurate interaction energies for binding motifs commonly found in organic and biomolecular systems. Reference data from the newly developed S66 database of interaction energies are used for this assessment, and a further set of 38 complexes is used as a test set for SCS methods developed herein. The strongly basis set-dependent nature of MP2 is confirmed in this study, with the SCS technique greatly reducing this behavior. It is found in this work that the spin component scaling technique can effectively be used to dramatically improve the performance of MP2 and MP2 variants, with overall errors being reduced by factors of about 1.5-2. SCS versions of all MP2 variants tested here are shown to give similarly accurate overall results.

The experimental electron density distribution (EDD) in 8-hydroxyquinoline cocrystallized with salicylic acid, 1, has been determined from a multipole refinement of high-resolution X-ray diffraction data collected at 100 K. The experimental EDD is compared with theoretical densities resulting from high-level ab initio and BHandH calculations using Atoms in Molecules theory. 1 crystallizes in the triclinic crystal system, and the asymmetric unit consists of a neutral salicylic acid molecule, a salicylate anion, and an 8-hydroxyquinolinium cation exhibiting a number of inter- and intramolecular hydrogen bonds and π-π interactions. Topological analysis reveals that π-π interactions are of the "closed-shell" type, characterized by rather low and flat charge density. In general, the agreement of the topological values (ρ(bcp) and ∇(2)ρ(bcp)) between experiment and theory is good, with mean differences of 0.010 e Å(-3) and 0.036 e Å(-5), respectively. The energetics of the π-π interactions have been estimated, and excellent agreement is observed between the relative energy and the strength of π-stacking derived from the Espinosa approach, with an average difference of only 4.4 kJ mol(-1).

The solid state structures of three compounds that contain a perfluorinated chain, CF3(CF2)(5)CH2CH(CH3)CO2H, CF3(CF2)(5)(CH2)(4)(CF2)(5)CF3 and {CF3(CF2)(5)CH2CH2}(3)P=O have been compared and a number of C-F center dot center dot center dot F-C and C-F center dot center dot center dot H-C interactions that are closer than the sum of the van der Waals radii have been identified. These interactions have been probed by a comprehensive computational chemistry investigation and the stabilizing energy between dimeric fragments was found to be 0.26-29.64 kcal/mol, depending on the type of interaction. An Atoms-in-Molecules (AIM) study has confirmed that specific C-F center dot center dot center dot F-C interactions are indeed present, and are not due simply to crystal packing. The weakly stabilizing nature of these interactions has been utilized in the physisorption of a selected number of compounds containing long chain perfluorinated ponytails onto a perfluorinated self-assembled monolayer, which has been characterized by IRRAS (Infrared Reflection Absorption Spectroscopy).

Activation of the catalytically relevant complex [Cr(CO)4(1)] (1 = Ph2P(C3H6)PPh2) by Et3Al (TEA) leads to formation of the Cr(I) bis-arene complex [Cr(1-bis- 6-arene)]+, as revealed by EPR and DFT calculations. This bis-arene complex is formed by intramolecular rearrangement and coordination of Cr(I) to the ligand phenyl groups in aliphatic solvents following loss of CO, preventing release of Cr(I) into solution. By comparison in aromatic solvents (toluene), the [Cr(bis-tolyl)]+ complex is preferentially formed.

Density functional theory (DFT) calculations have been performed to determine the strength and geometry of intermolecular interactions of "piano-stool" ruthenium arene complexes, which show potential as anticancer treatments. Model complexes with methane and benzene indicate that the coordinated arene has C-H···π acceptor ability similar to that of free benzene, whereas this arene acts as a much stronger C-H donor or partner in π-stacking than free benzene. The source of these enhanced interactions is identified as a combination of electrostatic and dispersion effects. Complexes of Ru-arene complexes with base-pair step fragments of DNA, in which the arene has the potential to act as an intercalator, have also been investigated. Binding energies are found to be sensitive to the size and nature of the arene, with larger and more flexible arenes having stronger binding. π-stacking and C-H···π interactions between arene and DNA bases and hydrogen bonds from coordinated N-H to DNA oxygen atoms, as well as covalent Ru-N bonding, contribute to the overall binding. The effect of complexation on DNA structure is also examined, with larger rise and more negative slide values than canonical B-DNA observed in all cases.

The rates of catalytic oxidative decontamination of the chemical warfare agent (CWA) sulfur mustard (HD, bis(2-chlororethyl) sulfide) and a range (chloroethyl) sulfide simulants of variable lipophilicity have been examined using a hydrogen peroxide-based microemulsion system. SANS (small-angle neutron scattering), SAXS (small-angle X-ray scattering), PGSE-NMR (pulsed-gradient spin-echo NMR), fluorescence quenching, and electrospray mass spectroscopy (ESI-MS) were implemented to examine the distribution of HD, its simulants, and their oxidation/hydrolysis products in a model oil-in-water microemulsion. These measurements not only present a means of interpreting decontamination rates but also a rationale for the design of oxidation catalysts for these toxic materials. Here we show that by localizing manganese-Schiff base catalysts at the oil droplet-water interface or within the droplet core, a range of (chloroethyl) sulfides, including HD, spanning some 7 orders of octanol-water partition coefficient (K(ow)), may be oxidized with equal efficacy using dilute (5 wt. % of aqueous phase) hydrogen peroxide as a noncorrosive, environmentally benign oxidant (e.g., t(1/2) (HD) approximately 18 s, (2-chloroethyl phenyl sulfide, C(6)H(5)SCH(2)CH(2)Cl) approximately 15 s, (thiodiglycol, S(CH(2)CH(2)OH)(2)) approximately 19 s {20 degrees C}). Our observations demonstrate that by programming catalyst lipophilicity to colocalize catalyst and substrate, the inherent compartmentalization of the microemulsion can be exploited to achieve enhanced rates of reaction or to exert control over product selectivity. A combination of SANS, ESI-MS and fluorescence quenching measurements indicate that the enhanced catalytic activity is due to the locus of the catalyst and not a result of partial hydrolysis of the substrate.

Auxiliary basis sets for use in density fitting second-order Møller-Plesset perturbation theory and other correlated ab initio methods have been developed for the 4d transition metal elements Y-Tc and Rh-Pd (sets for Ru, Ag, and Cd are already available), to be used in conjunction with the correlation consistent basis sets with pseudopotentials cc-pVnZ-PP and aug-cc-pVnZ-PP. Correlation energy calculations for a test set of small- to medium-sized transition metal complexes encompassing a variety of oxidation states show that the error in using these auxiliary basis sets is around 3-4 orders of magnitude smaller than the error due to orbital basis set size. The effect of truncating the auxiliary basis sets to remove higher angular momentum functions is also considered.

A quantitative structure--property relationship (QPSR) for the octanol--water partition of platinum complexes was constructed using molecular descriptors derived from density functional (DFT) calculations. A dataset of partition data for 64 complexes, consisting of 43 square-planar platinum(II) and 21 octahedral platinum(IV) complexes, was drawn from literature sources. Not only does this dataset include considerable structural diversity of complexes considered but also a variety of techniques for the measurement of partition coefficients. These data were modeled using descriptors drawn from electrostatic potentials and hardness/softness indices projected onto molecular surfaces. This required initial descriptor selection using a genetic algorithm approach, followed by partial least-squares regression against log Po/w data. In this way, a statistically robust model was constructed, with errors of similar size to the variation in log Po/w from multiple experimental measurements. Implications of lipophilicity for cellular accumulation of Pt-based drugs, and hence for design of new drugs, are discussed, as is the uptake of metabolites of cisplatin.

Hartree-Fock, density functional, and MP2 methods are applied to the problem of designing neutral, bicyclic C3-symmetric cages incorporating interacting anion- and cation-binding sites which strongly bind NaCl as an ion contact pair. A large number of trial ligands L and their complexes L:NaCl are tested, with the focus on maximizing binding by (i) optimizing the cavity size and shape and (ii) varying the nature of the anion- and cation-binding functionalities. The corresponding complexes L:Cl(-) and L:Na(+) are also studied in some detail. An analysis of their structures and charge distributions helps to build a consistent picture of the requirements for a successful NaCl binding. The 'best' candidate ligand utilizes a tripodal triether-substituted amine N(CH2CH2OR-)3 to bind the sodium cation; three thiourea groups in a tripodal arrangement with a 1,3,5-trisubstituted benzyl spacer group {C6H3(CH2NHC [Formula: see text] XNH-)3 X=O,S} to bind chloride; and a -CH2CH2- spacer linking the two binding sites. A simple Quantitative Structure-Property analysis suggests that the binding cavity shape and size is near to the optimal one for this system.

The experimental electron density distributions (EDD) in tetrafluorophthalonitrile and tetrafluoroisophthalonitrile have been determined from a multipole refinement with use of accurate X-ray diffraction data collected at 100 K. As hydrogen atoms pose a serious challenge to a successful X-ray based EDD determination due to their diminishing diffraction power, the absence of any such atoms in the studied complexes is an important advantage. The experimental EDD is compared with theoretical densities resulting from high-level ab initio and DFT calculations using the atoms in molecules theory. Topological analysis of the electron density was used to compare the two different isomers and to estimate the similarity of identical functional groups in different crystalline environments. Comparison with theoretical results reveals subtle differences in C−F bonds. The experimental molecular electrostatic potential satisfactorily explains the observed differences in the patterns of weak intermolecular interactions.

The experimental charge density distribution in crystalline 9-ethynyl-9-fluorenol has been determined in a refinement of a pseudo-atomic multipolar expansion (Hansen−Coppens formalism) against extensive low-temperature (T = 100 K) single-crystal X-ray diffraction data and compared with a selection of theoretical DFT calculations on the same complex. The molecule crystallizes in the centrosymmetric space group C2/c with two independent molecules in the asymmetric unit. A range of multipole models of varying complexity were tested and found to describe the observed intensities almost equally well in terms of the usual residual values presented; however, the resulting total density distributions and derived properties, such as atomic charges and molecular electrostatic potentials, showed significant differences and it is emphasized that care has to be taken when parameters used for the refinements are selected. In addition to the two medium-strength OH---O hydrogen bonds, which are found to differ between mo...

The partitioning of organic compounds between air and foliage and between water and foliage is of considerable environmental interest. The purpose of this work is to show that partitioning into the cuticular matrix of one particular species can be satisfactorily modeled by general equations we have previously developed and, hence, that the same general equations could be used to model partitioning into other plant materials of the same or different species. The general equations are linear free energy relationships that employ descriptors for polarity/polarizability, hydrogen bond acidity and basicity, dispersive effects, and volume. They have been applied to the partition of 62 very varied organic compounds between cuticular matrix of the tomato fruit, Lycopersicon esculentum, and either air (MXa) or water (MXw). Values of log MXa covering a range of 12.4 log units are correlated with a standard deviation of 0.232 log unit, and values of log MXw covering a range of 7.6 log unit are correlated with an SD ...

A previously published method for the prediction of molecular linear free energy relationship descriptors is tested against experimentally determined partition coefficients in various solvent systems. Sets of partition data between water and octanol, cyclohexane, and chloroform were taken from the literature. For each set of partition data used, r2 values ranged from 0.8 to 0.9 and RMS errors from 0.7 to 1.0 log unit, comparable to errors obtained with previously published models for octanol-water partition. Modified solvation equations for water-octanol and water-cyclohexane partition are presented, and their implications discussed. The possibility of applying the current approach to a wide range of solvation and transport properties is put forward.

Additive models for the estimation of Abraham's molecular descriptors R2, π2H, Σα2H, Σβ2H, Σβ2O, and log L16 have been developed. For five of the six descriptors, one set of 81 atom and functional group fragments is capable of reproducing experimentally derived results with correlation coefficients ranging from 0.95 to 0.99. However, one descriptor, Σα2H, required an entirely separate set of 51 fragments to be developed, resulting in a correlation coefficient of 0.97. Of particular importance is the speed of calculation (approximately 700 molecules/min), allowing so-called “high-throughput screening”. Several applications of this model for molecules containing intramolecular interactions are discussed.

Quantum chemical methods are applied in order to estimate the strain contribution to basicity in diamine proton sponges. Three methods of estimating the strain induced by nitrogen lone pair−lone pair repulsion, are discussed. Strain values in five specific compounds, 1,8-bis(dimethylamino)naphthalene, 4,5-bis(dimethylamino)phenanthrene, 4,5-bis(dimethylamino)fluorene, 1,8-bis(dimethylamino)-2,7-dimethoxynaphthalene, and 1,10-bis(dimethylamino)anthracene, are estimated at the HF/6-31G** and BLYP/6-31G** levels of theory. At the Hartree−Fock (HF) level, the values computed for these five compounds vary widely, from 32 to 84 kJ mol-1. The BLYP (electron-correlated) calculations indicate that the HF method overestimates strain values by (on average) around 18 kJ mol-1. None of the three methods discussed here are applicable to every type of proton spongecertain compounds in which the basic centers are part of heterocyclic systems seem to require some other approach.

Lennard-Jones was among the earliest to stress the dominant role played by the exclusion principle in chemistry and was the first to exploit the properties of the same-spin pair density to demonstrate the most probable spatial distribution of a given number of electron pairs. This paper demonstrates that a related distribution function, the conditional probability for same-spin electrons, is so successful in recovering the geometrical models associated with differing numbers of electron pairs, as suggested by the work of Lennard-Jones and subsequently adopted as the basis for the VSEPR model, that we propose that it be called the Lennard-Jones function, or LJF. The maxima in LJF show where the density of the other electrons is most likely to be found, relative to a fixed position of a same-spin reference electron. The digonal, trigonal, tetrahedral, bipyramidal, and octahedral patterns of maxima obtained in such displays demonstrate that these are the most probable arrangements for corresponding numbers o...

Correlated electronic structure calculations, coupled with atoms in molecules analysis, have been employed in a study of proton transfer in ionic hydrogen bonds. The isoelectronic series FHF-, H3O2-, H5O2+, and N2H7+ are used as models for such processes. Calculations at the MP2/6-311++G** level on the minimum energy structure and the transition state for proton transfer give an estimate of the barrier to proton transfer. Decomposition of the resulting charge distributions and energetics using Bader's techniques provides a deeper understanding of the electronic factors determining proton transfer barriers. It also indicates a fundamental difference between anionic and cationic hydrogen bonds.

The structures of 1,8-bis(dimethylamino)naphthalene and its protonated forms have been determined by ab initio geometry optimization. The title compound is found to possess C 2 symmetry in the gas phase, and the N(C 10 H 6 )N fragment is markedly nonplanar. Protonation causes the molecule to become more planar, as it approaches (without quite attaining) C 2v symmetry. Asymmetric protonation at one nitrogen is energetically preferred to the symmetric N-H-N bridged form. The predicted proton affinity is within a few kilojoules per mole of an experimental value. The changes in structure and the electron distribution are discussed in terms of the topology of the charge density g and of ⊇ 2 g, for this and related amines

Models of the hydrophobicity of platinum drugs based on exposed surface areas of polar and nonpolar atoms are presented. For a total of 24 log P(oct) data, the best model resulted in a standard deviation of 0.35 over a range of more than 4 log units, with regression coefficients in broad agreement with previous models of log P(oct) for organic molecules. This model is used to compare log P(oct) to cell uptake for five platinum drugs and hence to establish an exponential relation between these parameters.