Molecular Electrostatic Potential Minimum Research Articles

Molecular Electrostatic Potential Topology Analysis of Noncovalent Interactions.

ConspectusThe topology of molecular electrostatic potential (MESP), V(r), derived from a reliable quantum chemical method has been used as a powerful tool for the study of intermolecular noncovalent interactions. The MESP topology mapping is achieved by computing both ∇V(r) data and the elements of the Hessian matrix at ∇V(r) = 0, the critical point. MESP minimum (Vmin) as well as MESP at a reaction center, specific to an atom (Vn), have been employed as electronic parameters to interpret the variations in the reactivity (activation/deactivation) of chemical systems with respect to the influence of substituents, ligands, π-conjugation, aromaticity, trans influence, hybridization effects, steric effects, cooperativity, noncovalent interactions, etc. In this Account, several studies involving MESP topology analysis, which yielded interpretations of various noncovalent interactions and also provided new insights in the area of chemical bonding, are highlighted. The existence of lone pairs in molecules is distinctly reflected by the topology features of the MESP minima (Vmin). The Vmin is able to probe lone pairs in molecules, and it has been used as a reliable electronic parameter to assess their σ-donating power. Furthermore, MESP topology analysis can be used to forecast the structure and energetics of lone pair π-complexes. The MESP approach to rationalize lone pair interactions in molecular systems has led to the design of cyclic imines for CO2 capture. The MESP topology analysis of intermolecular complexes revealed a hitherto unknown phenomenon in chemical bonding theory─formation of a covalent bond due to the influence of a noncovalent bond. The MESP-guided approach to intermolecular interactions provided a successful design strategy for the development of CO2 capture systems. The MESP parameters Vmin and MESP at the nucleus, Vn, derived for the molecular systems have been used as powerful measures for the extent of electron donor-acceptor (eDA) interactions in noncovalent complexes. Noncovalent bond formation leads to more negative MESP at the acceptor nucleus (VnA) and less negative MESP at the donor nucleus (VnD). The strong linear relationship observed between ΔΔVn = ΔVnD - ΔVnA and bond energy suggested that MESP data provide a clear evidence of bond formation. Furthermore, MESP topology studies established a cooperativity rule for understanding the donor-acceptor interactive behavior of a dimer D...A with a third molecule. According to this, the electron reorganization in the dimer due to the eDA interaction enhances electron richness at "A", the acceptor, and enhances electron deficiency at "D", the donor. Resultantly, D in D...A is more accepting toward trimer formation, while A in D...A is more donating. MESP topology offers promising design strategies to tune the electron-donating strength in various noncovalent interactions in hydrogen-, dihydrogen-, halogen-, tetrel-, pnicogen-, chalcogen-, and aerogen-bonded complexes and thereby to predict the interactive behavior of molecules. To sum up, MESP topology analysis has become one of the most effective modern techniques for understanding, interpreting, and predicting the intermolecular interactive behavior of molecules.

Quantum Mechanical Methods for Thermal Hazard Risk Assessment in Early Phase Pharmaceutical Development

Quantum mechanical (QM) applications to predict heat of reaction (ΔHr) and thermal stability of strained aminocarbocylic salts, diazo compounds, and nitroalkanes for early phase thermal hazard risk assessment is presented. We provide examples on the use of explicit solvation to predict accurate ΔHr. Based on the QM calculations, the criticality class of a copper-catalyzed C–N coupling reaction is determined according to Stoessel’s reaction criticality class and the predictions are consistent with RC1 calorimetric experiment. We emphasize that to predict accurate ΔHr, it is important to consider the roles of reagents and solvents in QM calculations rather than simply considering the bond formation and bond breaking steps involved with reactants and products. Further, the use of predicted ΔHr for salt formation is applied to predict the thermal stability of bromoacetylene azetidine compounds to establish structure–stability relationship which would be useful to identify stable salt intermediates for safe reaction design. A strong correlation between ΔHr and the left limit of the DSC onset temperature (Tinit, °C) of the of exothermic peak is identified (Tinit = −2.85 ΔHr − 99.5). We propose that this model can be used as a prediction tool for novel azetidine salts to provide an estimate of thermal stability before synthesis. In this paper, for the first time we report molecular electrostatic potential (MESP) descriptor for the prediction of Tinit of diazo compounds. The deepest MESP minimum (Vmin) on the diazo group is considered as a probe to quantify the variation in structural effects. A strong correlation between Vmin and Tinit is found which would provide a new way of interpreting the thermal stability of novel diazo molecules just based on chemical structure. Further, the applicability of Vmin is verified on another set of compounds (nitroalkanes) and a good correlation is obtained. The structure–stability relationships that involves Vmin can be a useful QM descriptor for thermal stability prediction of a variety of molecules.

Clustering of carbon dioxide around zinc oxide cluster

The clustering and energetics of adsorption of CO2 on zinc oxide cage are investigated using dispersion corrected density functional theoretical method. The gas molecules are adsorbed over the cage by van der Waals interaction. The interaction energy is increased uniformly until the adsorption of twenty-five molecules of CO2 which belongs to the first coordination shell of the cage. A correlation between stabilization energy and the molecular electrostatic potential minimum (Vmin) indicating that less electron rich nature of oxygens of the cage promotes adsorption of CO2. Quantum theory of atoms in molecules analysis substantiated weak interactions between the adsorbed CO2 molecules.

Theoretical study of hydrogen bonding interactions in substituted nitroxide radicals

Interaction energy (Eint) of hydrogen bonded complexes of nitroxide radicals can be assessed in terms of the deepest minimum of molecular electrostatic potential (Vmin).

Absorption and emission properties of 5-phenyl tris(8-hydroxyquinolinato) M(III) complexes (M = Al, Ga, In) and correlations with molecular electrostatic potential.

Substituent effect for a series of 5-phenyl tris(8-hydroxyquinolinato) M(III) complexes (Mq3) of aluminum, gallium, and indium are investigated using density functional theory (DFT) for the ground state properties and the time-dependent version of DFT (TDDFT) for their absorption and emission properties. A comparison between the ground state energy of mer and fac isomers of all the complexes revealed that the mer configuration is always more stable than fac. The substituent effect is significantly reflected at the fluorescence maximum (λF ) values whereas the effect is moderate at the absorption maximum (λabs ) values. The molecular electrostatic potential (MESP) at the metal center (VM ) and the most electron rich region indicated by MESP minimum (Vmin ), located at the oxygen of phenoxide ring exhibit excellent correlations with the λF and Stokes shift (λF -λabs ) values. The study suggests the use of Stokes shift as an experimental quantity to measure the excited state substituent effect while the Vmin or VM emerge as theoretical quantities to measure the same.

Electrostatic Topographical Viewpoint of π-Conjugation and Aromaticity of Hydrocarbons.

A molecular electrostatic potential (MESP) topographical study has been conducted for a variety of conjugated hydrocarbons at B3LYP/6-311+G(d,p) level of theory to understand their π-conjugation features and aromaticity. The value of MESP minimum (Vm) is related to the localized and delocalized distribution of π-electron density. The Vm values are located interior to the rings in polycyclic benzenoid hydrocarbons (PBHs), whereas they lie outside the boundary of the rings in antiaromatic and in fused systems consisting of aromatic and antiaromatic moieties. The Vm points lie on top and bottom of the π-regions in linear polyenes and annulenes, while a degenerate distribution of CPs around the midpoint region of triple bonds is observed in alkynes. The eigenvalues λ1, λ2, and λ3 of the Hessian matrix at Vm(MESP minima) are used to define the aromatic character of the cyclic structures. The eigenvalues follow the trend λ1 ≫ λ2 > λ3 ≅ 0 in PBHs, λ1 > λ2 > λ3 ≅ 0 in linear polyenes, and λ1 > λ2 > λ3 ≠ 0 in antiaromatic systems. The difference in the aromatic character of PBHs from that of benzene is related to the deviations Δλ1, Δλ2, and Δλ3. The total deviation ∑i=13Δλi is found to be ≤ 0.011 au for all aromatic systems and lies between 0.011 and 0.035 au for all nonaromatic systems. For antiaromatic systems, its value is found to be above 0.035 au. Further, ∑i=13Δλi gives a direct interpretation of Clar's aromatic sextet structures for PBHs. In summary, MESP topography mapping is a powerful technique to quantify the localized and delocalized π-electron distribution in a variety of unsaturated hydrocarbon systems.

Electronic Structure of Bis(4‐dimethylaminophenyl)squaraine

AbstractThe structural and electronic features of bis(4‐dimethylaminophenyl)squaraine (1) has been studied using density functional BLYP/ cc‐pVTZ level of theory. The quinoid character of 1 is correlated to the partial double bond character of C‐NMe2 (1.379 Å) and C−O (1.236 Å) bonds which leads to accumulation of positive charge on NMe2 groups and negative charge on carbonyl oxygen. Further, the diagonal C1 C3 (2.086 Å) and C2 C4 (2.116 Å) distances of the squaric ring indicated a 1,3 type C−C orbital interaction. Molecular electrostatic potential (MESP) topographical analysis confirmed the charge separated quadrupolar nature of 1. The MESP minimum, Vmin located at the carbonyl oxygen, −62.5 kcal/mol, confirmed its highly electron rich character arising from the quinoid structure. The electronic structure of 1 revealed from MESP confirmed its quadrupolar nature and suggested the location of positive charge on NMe2 groups. The typically used chemical structure drawing of 1 showing +2 charge on the squaraine ring is inaccurate and misleading. The solvatochromic behaviour of 1 can be attributed to its quadrupolar electronic structure wherein the electron rich carbonyl groups provide room for noncovalent interactions with multiple solvent molecules.

Effect of Ligands on the Lewis Acidity of the Metal and the Binding of N‐Bases to Iridium Pincer Complexes

The coordination of pyridine (Py) and benzonitrile (PhCN) to benzene based pincer hydridochlorides [(PCP)IrH(Cl)] (1), [(POCOP)IrH(Cl)] (2), [{EtO(O)C‐POCOP}IrH(Cl)] (3), and [(PCN)IrH(Cl)] (4) was studied spectroscopically and computationally to deduce the ligand influence. The variable temperature NMR (1H, 31P, 15N) and UV/Visible spectroscopic measurements revealed preferential coordination of these N‐donor ligands in the apical position of 1–4 and gave the formation enthalpies for the hexacoordinate complexes, which follow the order: 1 ≈ 4 > 3 > 2. This order nicely agrees with the order of Lewis acidity obtained for these complexes in DFT calculations. The orbital and electron density distribution analysis were performed at the DFT/M06 theory level for 1–4 and a series of p‐substituted PCP‐based hydridochlorides. The increasing Lewis acidity of iridium [as a maximum energy, VS,max, of molecular electrostatic potential (MEP)] correlates with decreasing basicity of Cl‐ligand (as MEP minimum, VS,min) as well as with Hammett σp parameters of p‐substituents. Importantly, these properties are conserved upon conversion into the corresponding dihydrides, as shown on the example of 1 and 4.

Unveiling electrostatic portraits of quinones in reduction and protonation states

Quinones are known to perform diverse functions in a variety of biological and chemical processes as well as molecular electronics owing to their redox and protonation properties. Electrostatics chiefly governs intermolecular interaction behaviour of quinone states in such processes. The electronic distribution of a prototypical quinone, viz., p-benzoquinone, with its reduction and protonation states (BQS) is explored by molecular electrostatic potential (MESP) mapping using density functional theory. The reorganization of electronic distribution of BQS and their interaction with electrophiles are assessed for understanding the movement of ubiquinone in bacterial photosynthetic reaction centre, by calculating their binding energy with a model electrophile viz., lithium cation ( $$\hbox {Li}^{+}$$ ) at B3LYP/6-311+G(d,p) level of theory. The changes in the values of the MESP minima of BQS states alter their interacting behaviour towards $$\hbox {Li}^{+}$$ . A good correlation is found between the value of MESP minimum of BQS and the $$\hbox {Li}^{+}$$ binding strength at the respective site. To acquire more realistic picture of the proton transfer process to quinone with respect to its reduction state in the photosynthetic reaction center, interaction of BQS with model protonated motifs of serine, histidine as well as $$\hbox {NH}_{4}^{+}$$ is explored. Further, the electronic conjugation of the reduced states of 9,10-anthraquinone is probed through MESP for understanding the switching nature of their electronic conductivity. Quinones perform important function of proton transfer in photosynthesis and also act as a switch in molecular electronics. This work explores the electronic distribution of reduction and protonation states of p-benzoquinone using molecular electrostatic potential, for understanding the mechanisms of quinone activity in the photosynthesis and its switching nature in electronic conductivity.

Electrostatics for probing lone pairs and their interactions.

The value of the molecular electrostatic potential minimum (Vmin ) and its topographical features (position, as well as the eigenvalues and eigenvectors of the corresponding Hessian matrix) are recently proposed as the criteria for characterizing a lone pair (Kumar A. et al., J. Phys. Chem. 2014, A118, 526). This electrostatic characterization of lone pairs is examined for a large number of small molecules employing MP4/6-311++G(d,p)//MP2/6-311++G(d,p) theory. The eigenvector of the Hessian matrix corresponding to its largest eigenvalue (λmax ), is found to be directed toward the lone pair-bearing-atom, with λmax showing a strong linear correlation with Vmin . Large magnitudes of Vmin and λmax indicate a charge-dense lone pair. The topographical features of Vmin are seen to provide insights into the interactive behavior of the molecules with model electrophiles, viz. HF, CO2 , and Li+ . In all the complexes of HF and majority of the other complexes, the interaction energy (Eint ) correlates well with the respective Vmin, value, but for some deviations occurring due to other competing secondary interactions. The electrostatic interactions are found to be highly directional in nature as the orientation of interacting atom correlates strongly to the position of lone pair. In summary, the present study on a large number of test molecules shows that electrostatics is able to probe lone pairs in molecules and offers a simple interpretation of chemical reactivity. © 2017 Wiley Periodicals, Inc.

A Molecular Electrostatic Potential Analysis of Hydrogen, Halogen, and Dihydrogen Bonds

Hydrogen, halogen, and dihydrogen bonds in weak, medium and strong regimes (<1 to ∼ 60 kcal/mol) have been investigated for several intermolecular donor-acceptor (D-A) complexes at ab initio MP4//MP2 method coupled with atoms-in-molecules and molecular electrostatic potential (MESP) approaches. Electron density ρ at bond critical point correlates well with interaction energy (Enb) for each homogeneous sample of complexes, but its applicability to the entire set of complexes is not satisfactory. Analysis of MESP minimum (V(min)) and MESP at the nuclei (Vn) shows that in all D-A complexes, MESP of A becomes more negative and that of D becomes less negative suggesting donation of electrons from D to A leading to electron donor-acceptor (eDA) interaction between A and D. MESP based parameter ΔΔVn measures donor-acceptor strength of the eDA interactions as it shows a good linear correlation with Enb for all D-A complexes (R(2) = 0.976) except the strongly bound bridged structures. The bridged structures are classified as donor-acceptor-donor complexes. MESP provides a clear evidence for hydrogen, halogen, and dihydrogen bond formation and defines them as eDA interactions in which hydrogen acts as electron acceptor in hydrogen and dihydrogen bonds while halogen acts as electron acceptor in halogen bonds.

Lone Pairs: An Electrostatic Viewpoint

A clear-cut definition of lone pairs has been offered in terms of characteristics of minima in molecular electrostatic potential (MESP). The largest eigenvalue and corresponding eigenvector of the Hessian at the minima are shown to distinguish lone pair regions from the other types of electron localization (such as π bonds). A comparative study of lone pairs as depicted by various other scalar fields such as the Laplacian of electron density and electron localization function is made. Further, an attempt has been made to generalize the definition of lone pairs to the case of cations.

Designing metal hydride complexes for water splitting reactions: a molecular electrostatic potential approach.

The hydridic character of octahedral metal hydride complexes of groups VI, VII and VIII has been systematically studied using molecular electrostatic potential (MESP) topography. The absolute minimum of MESP at the hydride ligand (Vmin) and the MESP value at the hydride nucleus (VH) are found to be very good measures of the hydridic character of the hydride ligand. The increasing/decreasing electron donating feature of the ligand environment is clearly reflected in the increasing/decreasing negative character of Vmin and VH. The formation of an outer sphere metal hydride-water complex showing the HH dihydrogen interaction is supported by the location and the value of Vmin near the hydride ligand. A higher negative MESP suggested lower activation energy for H2 elimination. Thus, MESP features provided a way to fine-tune the ligand environment of a metal-hydride complex to achieve high hydridicity for the hydride ligand. The applicability of an MESP based hydridic descriptor in designing water splitting reactions is tested for group VI metal hydride model complexes of tungsten.

Trans and Cis Influences in Hypervalent Iodine(III) Complexes: A DFT Study

Trans and cis influences of various X ligands in two isomeric structures of acyclic hypervalent compound Ph[XI(OH)] and heterocyclic λ(3)-iodane Ph[(heterocycle)I(OH)] have been investigated on the basis of I-OH bond distance (d), electron density at I-OH bond critical point (ρ), I-OH stretching frequency (ν), and molecular electrostatic potential minimum (Vmin) at the OH lone pair. d, ρ, ν, and Vmin are found to be good parameters for quantifying trans and cis influences, and among them, Vmin is the most sensitive parameter. Heterocyclic λ(3)-iodanes showed a smaller trans influence than acyclic λ(3)-iodanes. All systems showed higher trans influence than cis influence while relative order of both is in accordance with the inductive nature of the ligands. Among the heterocyclic λ(3)-iodanes, strong trans/cis influence is observed with N or B in the ring while P gave moderate and S gave weak trans/cis influence. Among the substituents on the cis-positioned phenyl ring in heterocyclic λ(3)-iodanes, electron withdrawing ortho substitution significantly strengthened the hypervalent I-OH bond. The stability of a product resulting from the nucleophilic attack of Cl(-) on a λ(3)-iodane is directly correlated with the trans/cis influence of the ligands. This relationship is helpful to make good prediction on the interaction energy of a nucleophile in trivalent hypervalent iodine complex and hence useful in designing stable acyclic and heterocyclic hypervalent complexes.

Molecular electrostatics for probing lone pair–π interactions

An electrostatics-based approach has been proposed for probing the weak interactions between lone pair containing molecules and π deficient molecular systems. For electron-rich molecules, the negative minima in molecular electrostatic potential (MESP) topography give the location of electron localization and the MESP value at the minimum (Vmin) quantifies the electron-rich character of that region. Interactive behavior of a lone pair bearing molecule with electron deficient π-systems, such as hexafluorobenzene, 1,3,5-trinitrobenzene, 2,4,6-trifluoro-1,3,5-triazine and 1,2,4,5-tetracyanobenzene explored within DFT brings out good correlation of the lone pair-π interaction energy (E(int)) with the Vmin value of the electron-rich system. Such interaction is found to be portrayed well with the Electrostatic Potential for Intermolecular Complexation (EPIC) model. On the basis of the precise location of MESP minimum, a prediction for the orientation of a lone pair bearing molecule with an electron deficient π-system is possible in the majority of the cases studied.

Accurate Prediction of Cation−π Interaction Energy Using Substituent Effects

Substituent effects on cation-π interactions have been quantified using a variety of Φ-X···M(+) complexes where Φ, X, and M(+) are the π-system, substituent, and cation, respectively. The cation-π interaction energy, E(M(+)), showed a strong linear correlation with the molecular electrostatic potential (MESP) based measure of the substituent effect, ΔV(min) (the difference between the MESP minimum (V(min)) on the π-region of a substituted system and the corresponding unsubstituted system). This linear relationship is E(M(+)) = C(M(+))(ΔV(min)) + E(M(+))' where C(M(+)) is the reaction constant and E(M(+))' is the cation-π interaction energy of the unsubstituted complex. This relationship is similar to the Hammett equation and its first term yields the substituent contribution of the cation-π interaction energy. Further, a linear correlation between C(M(+))() and E(M(+))()' has been established, which facilitates the prediction of C(M(+)) for unknown cations. Thus, a prediction of E(M(+)) for any Φ-X···M(+) complex is achieved by knowing the values of E(M(+))' and ΔV(min). The generality of the equation is tested for a variety of cations (Li(+), Na(+), K(+), Mg(+), BeCl(+), MgCl(+), CaCl(+), TiCl(3)(+), CrCl(2)(+), NiCl(+), Cu(+), ZnCl(+), NH(4)(+), CH(3)NH(3)(+), N(CH(3))(4)(+), C(NH(2))(3)(+)), substituents (N(CH(3))(2), NH(2), OCH(3), CH(3), OH, H, SCH(3), SH, CCH, F, Cl, COOH, CHO, CF(3), CN, NO(2)), and a large number of π-systems. The tested systems also include multiple substituted π-systems, viz. ethylene, acetylene, hexa-1,3,5-triene, benzene, naphthalene, indole, pyrrole, phenylalanine, tryptophan, tyrosine, azulene, pyrene, [6]-cyclacene, and corannulene and found that E(M)(+) follows the additivity of substituent effects. Further, the substituent effects on cationic sandwich complexes of the type C(6)H(6)···M(+)···C(6)H(5)X have been assessed and found that E(M(+)) can be predicted with 97.7% accuracy using the values of E(M(+))' and ΔV(min). All the Φ-X···M(+) systems showed good agreement between the calculated and predicted E(M(+))() values, suggesting that the ΔV(min) approach to substituent effect is accurate and useful for predicting the interactive behavior of substituted π-systems with cations.

Assessment of Stereoelectronic Factors That Influence the CO2Fixation Ability of N-Heterocyclic Carbenes: A DFT Study

The CO(2) fixation ability of N-heterocyclic carbenes (NHC) has been assessed on the basis of electronic and steric properties of the N- and C-substituents, measured in terms of molecular electrostatic potential minimum, observed at the carbene lone pair region of NHC (V(min1)) as well as at the carboxylate region of the NHC-CO(2) adduct (V(min2)). Both V(min1) and V(min2) are found to be simple and efficient descriptors of the stereoelectronic effect of NHCs. The V(min)-based analysis also proved that the stereoelectronic effect of N- and C-substituents is additive. When only C-substituents are present in NHC, its CO(2) affinity solely depends on the electronic effect, whereas if the N-center bears the substituents, the steric factor plays a major role in the carboxylation/decarboxylation process. For standard substituents, maximum CO(2) binding energy of 18.0 kcal/mol is observed for the most electron-donating combination of NMe(2) as the C-substituent and Me as the N-substituent. Introduction of ring strain through five-membered ring fusion at the NC bond slightly increased the electron-rich character of the carbene lone pair and also enhanced the CO(2) binding energy to 20.9 kcal/mol. To further improve the CO(2) fixing ability of NHCs, we have proposed the use of CH(2)OH, CH(2)NHCOMe, and CH(2)NHPh as N-substituents, as they participate in intramolecular hydrogen bond interaction with the carboxylate. With the new strategy, considerable improvement in the CO(2) binding energy (26.5 to 33.0 kcal/mol) is observed.

Quantification of the Trans Influence in Hypervalent Iodine Complexes

The trans influence of various X ligands in hypervalent iodine(III) complexes of the type CF(3)[I(X)Cl] has been quantified using the trans I-Cl bond length (d(X)), the electron density ρ(r) at the (3, -1) bond critical point of the trans I-Cl bond, and topological features of the molecular electrostatic potential (MESP). The MESP minimum at the Cl lone pair region (V(min)) is a sensitive measure of the trans influence. The trans influence of X ligands in hypervalent iodine(V) complexes is smaller than that in iodine(III) complexes, while the relative ordering of this influence is the same in both complexes. In CF(3)[I(X)Y] complexes, the mutual trans influence due to the trans disposition of the X and Y ligands is quantified using the energy E(XY) of the isodesmic reaction CF(3)[I(X)Cl] + CF(3)[I(Y)Cl] → CF(3)[I(Cl)Cl] + CF(3)[I(X)Y]. E(XY) is predicted with good accuracy using the trans-influence parameters of X and Y, measured in terms of d(X), ρ(r), or V(min). The bond dissociation energy (E(d)) of X or Y in CF(3)[I(X)Y] is significantly influenced by the trans influence as well as the mutual trans influence. This is confirmed by deriving an empirical equation to predict E(d) using one of the trans-influence parameters (d(X), ρ(r), or V(min)) and the mutual trans-influence parameter E(XY) for a large number of complexes. The quantified values of both the trans influence and the mutual trans-influence parameters may find use in assessing the stability of hypervalent iodine compounds as well as in the design of new stable hypervalent complexes. Knowledge about the I-X bond dissociation energies will be useful for explaining the reactivity of hypervalent iodine complexes and the mechanism of their reactions.

Electronic structure, vibrational spectra and 1H NMR of halide ion (F −, Cl − and Br −) encapsulated bambus[6]uril from density functional theory

Molecular Interactions between novel Bambus[6]uril host (BU[6]) and halide ion (F −, Cl −, Br −) have been studied using the density functional theory. Molecular electrostatic potential (MESP) investigations in BU[6] have shown large electron-rich regions near carbonyls on portals than those near cavity of the host. Further MESP minima within cavity are shallow compared to those near portals of BU[6]. Vibrational spectra of isolated BU[6] and halide ion encapsulated BU[6] are derived. Normal mode analyses reveal that on encapsulation of halide ion within BU[6] cavity engenders a downshift of 12 cm −1 for 1757 cm −1 band assigned to stretching of carbonyls at host portals. Likewise the 1714 cm −1 vibration of isolated BU[6] arising from carbonyl stretching near host cavity shows a shift up to 5 cm −1 on complexation. 1H NMR chemical shifts in DMSO from B3LYP/6-31+G(d,p) theory predict large shielding for methyl protons. On the other hand methine protons directing toward the cavity are deshielded and follow the order: H c (methine protons) > H b (methylene) > H a (methyl) in the free host; which remains unchanged on complexation. These inferences are in consonant with the measured 1H NMR spectra (Svec et al., Angew. Chem. Int. Ed. 49 (2010) 2378). Subsequent structure and NMR chemical shifts in Cl −@BU[6] as well as those of isolated BU[6] obtained from a variety of functionals viz., B3LYP, X3LYP, PBE0, BMK and M-06L in density functional calculations, are compared. Structure and 1H NMR chemical shifts in DMSO from the calculations incorporating B3LYP or X3LYP functional generally agree better with experiment.

Quantitative Assessment of Substituent Effects on Cation−π Interactions Using Molecular Electrostatic Potential Topography

A molecular electrostatic potential (MESP) topography based approach has been proposed to quantify the substituent effects on cation-π interactions in complexes of mono-, di-, tri-, and hexasubstituted benzenes with Li(+), Na(+), K(+), and NH(4)(+). The MESP minimum (V(min)) on the π-region of C(6)H(5)X showed strong linear dependency to the cation-π interaction energy, E(M(+)). Further, cation-π distance correlated well with V(min)-π distance. The difference between V(min) of C(6)H(5)X and C(6)H(6) (ΔV(min)) is proposed as a good parameter to quantify the substituent effect on cation-π interaction. Compared to benzene, electron-donating groups stabilize the di-, tri-, and hexasubstituted cation-π complexes while electron-withdrawing groups destabilize them. In multiple substituted complexes, E(M(+)) is almost equal (∼95%) to the sum of the individual substituent contributions (E(M(+)) ≈ Σ(ΔE(M(+)))), suggesting that substituent effect on cation-π interactions is largely additive. The ΔV(min) of C(6)H(5)X systems and additivity feature have been used to make predictions on the interaction energies of 80 multiple substituted cation-π complexes with above 97% accuracy. The average mean absolute deviation of the V(min)-predicted interaction energy, E(M(+))(V) from the calculated E(M(+)) is -0.18 kcal/mol for Li(+), -0.09 kcal/mol for Na(+), -0.43 kcal/mol for K(+), and -0.67 kcal/mol for NH(4)(+), which emphasize the predictive power of V(min) as well as the additive feature of the substituent effect.