Solvent Effect on Dative and Ionic Bond Strengths: A Unified Theory from the Potential Analysis and Valence Bond (VB) Computation.

Solvent molecules interact with a solute through various intermolecular forces. Here we employed a potential energy surface (PES) analysis to interpret the solvent-induced variations in the strengths of dative (Me3NBH3) and ionic (LiCl) bonds, which possess both ionic and covalent (neutral) characteristics. The change of a bond is driven by the gradient (force) of the solvent-solute interaction energy with respect to the focused bond length. Positive force shortens the bond length and increases the bond force constant, leading to a blue-shift of the bond stretching vibrational frequency upon solvation. Conversely, negative force elongates the bond, resulting in a reduced bond force constant and red-shift of the stretching vibrational frequency. The different responses of Me3NBH3 and LiCl to solvation are studied with valence bond (VB) theory, as Me3NBH3 and LiCl are dominated by the neutral covalent VB structure and the ionic VB structure, respectively. The dipole moment of an ionic VB structure increases along the increasing bond distance, while the dipole moment of a neutral covalent VB structure increases with the decreasing bond distance. The roles of the dominating VB structures are further examined by the geometry optimizations and frequency calculations with the block-localized wavefunction (BLW) method.

Conformational Preference of Lithium Polysulfide Clusters Li2Sx (x = 4-8) in Lithium-Sulfur Batteries.

Structures are of fundamental importance for diverse studies of lithium polysulfide clusters, which govern the performance of lithium-sulfur batteries. The ring-like geometries were regarded as the most stable structures, but their physical origin remains elusive. In this work, we systematically explored the minimal structures of Li2Sx (x = 4-8) clusters to uncover the driving force for their conformational preferences. All low-lying isomers were generated by performing global searches using the ABCluster program, and the ionic nature of the Li···S interactions was evidenced with the energy decomposition analysis based on the block-localized wave function (BLW-ED) approach and further confirmed with the quantum theory of atoms in molecule (QTAIM). By analysis of the contributions of various energy components to the relative stability with the references of the lowest-lying isomers, the controlling factor for isomer preferences was found to be the polarization interaction. Notably, although the electrostatic interaction dominates the binding energies, it contributes favorably to the relative stabilities of most isomers. The Li+···Li+ distance is identified as the key geometrical parameter that correlates with the strength of the polarization of the Sx2- fragment imposed by the Li+ cations. Further BLW-ED analyses reveal that the cooperativity of the Li+ cations primarily determines the relative strength of the polarization.

The strength and selectivity of perfluorinated nano-hoops and buckybowls for anion binding and the nature of anion-π interactions.

Perfluorinated cycloparaphenylenes (F-[n]CPP, n = 5-8), boron nitride nanohoop (F-[5]BNNH), and buckybowls (F-BBs) were proposed as anion receptors via anion-π interactions with halide anions (Cl- , Br- and I- ), and remarkable binding strengths up to -294.8 kJ/mol were computationally verified. The energy decomposition approach based on the block-localized wavefunction method, which combines the computational efficiency of molecular orbital theory and the chemical intuition of ab initio valence bond theory, was applied to the above anion-π complexes, in order to elucidate the nature and selectivity of these interactions. The overall attraction is mainly governed by the frozen energy component, in which the electrostatic interaction is included. Remarkable binding strengths with F-[n]CPPs can be attributed to the accumulated anion-π interactions between the anion and each conjugated ring on the hoop, while for F-BBs, additional stability results from the curved frameworks, which distribute electron densities unequally on π-faces. Interestingly, the strongest host was proved to be the F-[5]BNNH, which exhibits the most significant anisotropy of the electrostatic potential surface due to the difference in the electronegativities of nitrogen and boron. The selectivity of each host for anions was explored and the importance of the often-overlooked Pauli exchange repulsion was illustrated. Chloride anion turns out to be the most favorable anion for all receptors, due to the smallest ionic radius and the weakest destabilizing Pauli exchange repulsion.

Optomechanical noise suppression with the optimal squeezing process.

Quantum squeezing-assisted noise suppression is a promising field with wide applications. However, the limit of noise suppression induced by squeezing is still unknown. This paper discusses this issue by studying weak signal detection in an optomechanical system. By solving the system dynamics in the frequency domain, we analyze the output spectrum of the optical signal. The results show that the intensity of the noise depends on many factors, including the degree or direction of squeezing and the choice of the detection scheme. To measure the effectiveness of squeezing and to obtain the optimal squeezing value for a given set of parameters, we define an optimization factor. With the help of this definition, we find the optimal noise suppression scheme, which can only be achieved when the detection direction exactly matches the squeezing direction. The latter is not easy to adjust as it is susceptible to changes in dynamic evolution and sensitive to parameters. In addition, we find that the additional noise reaches a minimum when the cavity (mechanical) dissipation κ(γ) satisfies the relation κ = Nγ, which can be understood as the restrictive relationship between the two dissipation channels induced by the uncertainty relation. Furthermore, by taking into account the noise source of our system, we can realize high-level noise suppression without reducing the input signal, which means that the signal-to-noise ratio can be further improved.

Selectivity Rule of Cryptands for Anions: Molecular Rigidity and Bonding Site.

Cryptands utilize inside CH or NH groups as hydrogen bond (H-bond) donors to capture anions such as halides. In this work, the nature and selectivity of confined hydrogen bonds inside cryptands were computationally analyzed with the energy decomposition scheme based on the block-localized wavefunction method (BLW-ED), aiming at an elucidation of governing factors in the binding between cryptands and anions. It was revealed that the intrinsic strengths of inward hydrogen bonds are dominated by the electrostatic attraction, while the anion preferences (selectivity) of inner CH and NH hydrogen bonds are governed by the Pauli exchange repulsion and electrostatic interaction, respectively. Typical conformers of cages are classified into two groups, including the C3(h) -symmetrical conformers, in which all halide anions are located near the centroids of cages, and the "semi-open" conformers, which exhibit shifted bonding sites for different halide anions. Accordingly, the difference in governing factors of selectivity is attributed to either the rigidity of cages or the binding site of anions for these two groups. In details, the C3 conformers of NH cryptands can be enlarged more remarkably than the C3(h) -symmetrical conformers of CH cryptands as the size of anion (ionic radius) increases, resulting in the relaxation of the Pauli repulsion and a dramatic reduction in electrostatic attraction, which eventually rules the selectivity of NH cryptands for halide anions. By contrary, the CH cryptands are more rigid and cannot effectively reduce the Pauli repulsion, which subsequently governs the anion preference. Unlike C3 conformers whose rigidity determines the selectivity, semi-open conformers exhibit different binding sites for different anions. From F- to I- , the bonding site shifts toward the outside end of the pocket inside the semi-open NH cryptand, leading to the significant reduction of the electrostatic interaction that dominates the anion preference. Differently, binding sites are much less affected by the size of anion inside the semi-open CH cryptand, in which the Pauli exchange repulsion remains the key factor for the selectivity of inner hydrogen bonds.

On the nature of inter-anion coinage bonds.

To explore the binding energy profiles and elucidate the bonding nature in counter-intuitive anion⋯anion coinage bonds (CiBs), thirty-one complexes were constructed, and the inter-anion CiBs were studied theoretically. The metastability was evidenced by the characteristic potential wells in six cases, demonstrating that anions [Au(CN)4]-, [Ag(CN)2]- and [AuO]- are appropriate building blocks for CiBs. The kinetic stability was further supported by ab initio molecular dynamics (AIMD) simulations and the analyses based on the local vibrational mode and quantum theory of atoms in molecules (QTAIM) methods. The anion⋯anion CiBs in the dimers of [AuCl4]- and [Au(CN)4]- previously observed in condensed phases were confirmed to be thoroughly repulsive under vacuum, but turned attractive in the crystal environment which was simulated using the solvation model based on density (SMD). However, the intrinsic strength of the inter-anion bonding is barely variated by the environment, as it is the combination of the inter-anion interaction and the environment effect that stabilizes the anion pairs. The block-localized wavefunction (BLW) method and its corresponding energy decomposition (BLW-ED) approach were further employed aiming at a chemically meaningful explanation for these counterintuitive phenomena. By inspecting the profiles of energy components, we identified the vital distinction between inter-anion CiBs and conventional non-covalent interactions lying in the electrostatic interaction, which variates nonmonotonically in the inter-anion complexes. The electrostatic interaction also dominates the depth of potential wells, which is commonly used to evaluate the kinetic stability, while Pauli exchange repulsion is the most repulsive factor preventing the formation of anion adducts. The importance of the Pauli exchange repulsion was further highlighted by comparing cases with and without metastability, in which the absence of a potential well is solely caused by the enhancement of the Pauli exchange repulsion.

Design, synthesis and SAR study of Fluorine-containing 3rd-generation taxoids.

It has been shown that the incorporation of fluorine or organofluorine groups into pharmaceutical and agricultural drugs often induces desirable pharmacological properties through unique protein-drug interactions involving fluorine. We have reported separately remarkable effects of the 2,2-difluorovinyl (DFV) group at the C3' position, as well as those of the CF3O and CHF2O groups at the 3-position of the C2-benzoyl moiety of the 2nd- and 3rd-generation taxoids on their potency and pharmacological properties. Thus, it was very natural for us to investigate the combination of these two modifications in the 3rd-generation taxoids and to find out whether these two modifications are cooperative at the binding site in the ß-tubulin or not, as well as to see how these effects are reflected in the biological activities of the new 3rd-generation DFV-taxoids. Accordingly, we designed, synthesized and fully characterized 14 new 3rd-generation DFV-taxoids. These new DFV-taxoids exhibited remarkable cytotoxicity against human breast, lung, colon, pancreatic and prostate cancer cell lines. All of these new DFV-taxoids exhibited subnanomolar IC50 values against drug-sensitive cell lines, A549, HT29, Vcap and PC3, as well as CFPAC-1. All of the novel DFV-taxoids exhibited 2-4 orders of magnitude greater potency against extremely drug-resistant cancer cell lines, LCC6-MDR and DLD-1, as compared to paclitaxel, indicating that these new DFV-taxoids can overcome MDR caused by the overexpression of Pgp and other ABC cassette transporters. Dose-response (kill) curve analysis of the new DFV-taxoids in LCC6-MDR and DLD-1 cell lines revealed highly impressive profiles of several new DFV-taxoids. The cooperative effects of the combination of the 3'-DFV group and 3-CF3O/CHF2O-benzoyl moiety at the C2 position were investigated in detail by molecular docking analysis. We found that both the 3'-DFV moiety and the 3-CF3O/3-CHF2O group of the C2-benzoate moiety are nicely accommodated to the deep hydrophobic pocket of the paclitaxel/taxoid binding site in the ß-tubulin, enabling an enhanced binding mode through unique attractive interactions between fluorine/CF3O/CHF2O and the protein beyond those of paclitaxel and new-generation taxoids without bearing organofluorine groups, which are reflected in the remarkable potency of the new 3rd-generation DFV-taxoids.

Hydrogen and Halogen Bonding in Homogeneous External Electric Fields: Modulating the Bond Strengths.

Recent years have witnessed various fascinating phenomena arising from the interactions of noncovalent bonds with homogeneous external electric fields (EEFs). Here we performed a computational study to interpret the sensitivity of intrinsic bond strengths to EEFs in terms of steric effect and orbital interactions. The block-localized wavefunction (BLW) method, which combines the advantages of both ab initio valence bond (VB) theory and molecular orbital (MO) theory, and the subsequent energy decomposition (BLW-ED) approach were adopted. The sensitivity was monitored and analyzed using the induced energy term, which is the variation in each energy component along the EEF strength. Systems with single or multiple hydrogen (H) or halogen (X) bond(s) were also examined. It was found that the X-bond strength change to EEFs mainly stems from the covalency change, while generally the steric effect rules the response of H-bonds to EEFs. Furthermore, X-bonds are more sensitive to EEFs, with the key difference between H- and X-bonds lying in the charge transfer interaction. Since phenylboronic acid has been experimentally used as a smart linker in EEFs, switchable sensitivity was scrutinized with the example of the phenylboronic acid dimer, which exhibits two conformations with either antiparallel or parallel H-bonds, thereby, opposite or consistent responses to EEFs. Among the studied systems, the quadruple X-bonds in molecular capsules exhibit remarkable sensitivity, with its interaction energy increased by -95.2 kJ mol-1 at the EEF strength 0.005 a.u.

The effect of asymmetric external reorganization energy on electron and hole transport in organic semiconductors.

Understanding the relationship between charge mobilities and the molecular stacking structures of π-conjugated organic semiconducting materials is essential for their development. In this study, a quantum mechanics (QM)-derived state-specific polarizable force field (SS-PFF) is applied to explicitly estimate the external reorganization energies (λext) during electron transfer (ET) or hole transfer (HT) processes using our recently proposed two-point model (J. Phys. Chem. A, 2018, 122, 8957-8964). Different from the Marcus two-sphere model, the application of the explicit two-point model produces a notably asymmetric λext for ET and HT processes in oligoacene crystals. For the same charge transfer channels, the λext of ET is 7-10 times higher than that of HT, which results in a larger intrinsic hole mobility. This successfully rationalizes why acenes are prone to be p-type conducting materials. Perfluorination can change the polarity of the molecular surface electrostatic potential (ESP). Thus, perfluorination is a possible approach to reduce the external reorganization energies for ET reactions, which can be used to tune the order of λext of ET and HT processes. The two-point model with the SS-PFF, therefore, opens the door to revisit the intrinsic mobilities of electrons and holes in organic semiconductors.

Classical Electrostatics Remains the Driving Force for Interanion Hydrogen and Halogen Bonding.

Interanion hydrogen bonding (IAHB) and halogen bonding (IAXB) have emerged as a counterintuitive linker in a range of fascinating applications. Despite the overall repulsive (positive) binding energy, anions are trapped in a local minimum with its corresponding transition state (TS) preventing dissociation. In other words, the adduct of anions is metastable. Seemingly, the electrostatic paradigm and force field description of hydrogen/halogen bonding (HB/XB) are challenged, because of the preconceived Coulombic repulsion. Aiming at an insightful understanding of these interanion phenomena, we employed the energy decomposition approach based on the block-localized wavefunction method (BLW-ED) to investigate a series of exemplary interanion complexes. As expected, the key distinction from the conventional HB/XB lies in the electrostatic interaction, which is not increasingly repulsive as anions gradually approach to each other. Rather, there is a Coulombic barrier at a certain point. After this point, the electrostatic repulsion diminishes with the decreasing distance between anions. Differently, other energy components vary monotonically just like in conventional cases. The nonmonotonic characteristic of the electrostatic interaction in interanion complexes was reproduced using the multipole expansion in AMOEBA polarizable force field in which the state-specified atomic multipoles were adopted. This suggests that the nonmonotonicity can be well interpreted by classical electrostatic theory and there is no conceptual difference between conventional HB/XB and IAHB/IAXB. The stability of IAHB/IAXB depends on the competition between the local attractive HB/XB and the global Coulombic repulsion of net charges, though there is cooperativity between these two contrasting forces. This concise model was supported by the attractive IAHB/IAXB in modified molecular capsules, which exhibit strong quadruple HB/XBs and a considerable distance between charged substituents.

Inter-anion chalcogen bonds: Are they anti-electrostatic in nature?

Inter-anion hydrogen and halogen bonds have emerged as counterintuitive linkers and inspired us to expand the range of this unconventional bonding pattern. Here, the inter-anion chalcogen bond (IAChB) was proposed and theoretically analyzed in a series of complexes formed by negatively charged bidentate chalcogen bond donors with chloride anions. The kinetic stability of IAChB was evidenced by the minima on binding energy profiles and further supported by ab initio molecular dynamic simulations. The block-localized wave function (BLW) method and its subsequent energy decomposition (BLW-ED) approach were employed to elucidate the physical origin of IAChB. While all other energy components vary monotonically as anions get together, the electrostatic interaction behaves exceptionally as it experiences a Coulombic repulsion barrier. Before reaching the barrier, the electrostatic repulsion increases with the shortening Ch⋯Cl- distance as expected from classical electrostatics. However, after passing the barrier, the electrostatic repulsion decreases with the Ch⋯Cl- distance shortening and subsequently turns into the most favorable trend among all energy terms at short ranges, representing a dominating force for the kinetic stability of inter-anions. For comparison, all energy components exhibit the same trends and vary monotonically in the conventional counterparts where donors are neutral. By comparing inter-anions and their conventional counterparts, we found that only the electrostatic energy term is affected by the extra negative charge. Remarkably, the distinctive (nonmonotonic) electrostatic energy profiles were reproduced using quantum mechanical-based atomic multipoles, suggesting that the crucial electrostatic interaction in IAChB can be rationalized within the classical electrostatic theory just like conventional non-covalent interactions.

The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes.

The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in ABCC3, CPS1, and TRIP6 gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients' poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.

Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth.

BACKGROUND: Prostate cancer (PCa) remains the second leading cause of cancer-related death among men. Taxanes, such as docetaxel and cabazitaxel are utilized in standard treatment regimens for chemotherapy naïve castration-resistant PCa. However, tumors often develop resistance to taxane chemotherapeutics, highlighting a need to identify additional therapeutic targets. Fatty acid-binding protein 5 (FABP5) is an intracellular lipid carrier whose expression is upregulated in metastatic PCa and increases cell growth, invasion, and tumor formation. Here, we assessed whether FABP5 inhibitors synergize with semi-synthetic taxanes to induce cytotoxicity in vitro and attenuate tumor growth in vivo. METHODS: PC3, DU-145, and 22Rv1 PCa cells were incubated with FABP5 inhibitors Stony Brook fatty acid-binding protein inhibitor 102 (SBFI-102) or SBFI-103 in the presence or absence of docetaxel or cabazitaxel, and cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay. Cytotoxicity of SBFI-102 and SBFI-103 was also evaluated in noncancerous cells. For the in vivo studies, PC3 cells were subcutaneously implanted into BALB/c nude mice, which were subsequently treated with FABP5 inhibitors, docetaxel, or a combination of both. RESULTS: SBFI-102 and SBFI-103 produced cytotoxicity in the PCa cells. Coincubation of the PCa cells with FABP5 inhibitors and docetaxel or cabazitaxel produced synergistic cytotoxic effects in vitro. Treatment of mice with FABP5 inhibitors reduced tumor growth and a combination of FABP5 inhibitors with a submaximal dose of docetaxel reduced tumor growth to a larger extent than treatment with each drug alone. CONCLUSIONS: FABP5 inhibitors increase the cytotoxic and tumor-suppressive effects of taxanes in PCa cells. The ability of these drugs to synergize could permit more efficacious antitumor activity while allowing for dosages of docetaxel or cabazitaxel to be lowered, potentially decreasing taxane-resistance.

Design, synthesis and SAR study of 3rd-generation taxoids bearing 3-CH3, 3-CF3O and 3-CHF2O groups at the C2-benzoate position.

It has been shown that inclusion of CF3O and CHF2O groups to drug candidates often improve their pharmacological properties, especially metabolic stability, membrane permeability and PK profile. Moreover, the unique non-spherical structure of the OCHF2 group can provide interesting and beneficial characteristics. Accordingly, new 3rd-generation taxoids, bearing 3-OCF3 or 3-OCF2H (and 3-CH3 for comparison) at the C2 benzoate moiety, were synthesized and their potencies against drug-sensitive and drug-resistant cancer cell lines examined. In this study, our previous SAR studies on 3rd-generation taxoids were expanded to disclose that CH3, CF3O and CHF2O groups are well tolerated at this position and enhance potency, especially against MDR-cancer cell lines so that these taxoids can virtually overcome MDR. These new taxoids exhibit up to 7 times higher cytotoxicity (IC50) than paclitaxel against drug-sensitive cancer cell lines (MCF7 and LCC6-WT) and 2-3 orders of magnitude higher potency than paclitaxel against drug-resistant ovarian, breast and colon cancer cell lines with MDR-phenotype (NCI/ADR, LCC6-MDR and LDL-1), as well as pancreatic cancer cell line, CFPAC-1. Since it has been shown that a bulky group at this position reduces potency, it is noteworthy that rather bulky CF3O and CHF2O groups are well tolerated. Molecular modeling analysis indicated the favorable van der Waals interactions of CF3O and CHF2O groups in the binding site. It is also worthy of note that new taxoids, bearing a CHF2O group at the C2 benzoate position (1-06 series), exhibited the highest potencies against MDR-cancer cell lines and cancer stem cell (CSC)-enriched cancer cell lines. These new 3rd-generation taxoids are promising candidates for highly potent chemotherapeutic agents, as well as payloads for tumor-targeting drug conjugates such as antibody-drug conjugates (ADCs).

Attraction between electrophilic caps: A counterintuitive case of noncovalent interactions.

Intermolecular attractive interaction between electrophilic sites is a counterintuitive phenomenon, as the electrostatic interaction therein is repulsive and destabilizing. Here, we confirm this phenomenon in four representative complexes, using state-of-the-art quantum mechanical methods. By employing the block-localized wavefunction (BLW) method, which can turn off intermolecular charge transfer interactions, we profoundly demonstrated the significance of charge transfer interactions in these seemingly counterintuitive complexes. Indeed, after being "turned off" the intermolecular charge transfer interaction in, for example, the FNSi···BrF complex, the originally attractive intermolecular interaction turns to be repulsive. The energy decomposition approach based on the BLW method (BLW-ED) can partition the overall stability gained on the formation of intermolecular noncovalent interaction into several physically meaningful components. According to the BLW-ED analysis, the electrostatic repulsion in these counterintuitive cases is overwhelmed by the stabilizing polarization, dispersion interaction, and most importantly, the charge transfer interaction, resulting in the eventual counterintuitive overall attraction. The present study suggests that, predicting bonding sites of noncovalent interactions using only the "hole" concept may be not universally sufficient, because other significant stabilizing factors will contribute to the stability and sometimes, play even bigger roles than the electrostatic interaction and consequently govern the complex structures. © 2018 Wiley Periodicals, Inc.

Classical Electrostatic Interaction Is the Origin for Blue-Shifting Halogen Bonds.

Studies have shown that, on the one hand, charge transfer (CT) plays a key role in halogen bonds (D···X-A) (D = donor; X = halogen atom; A = acceptor), suggesting considerable covalent character of halogen bonding. But, on the other hand, it has been proposed that halogen bonding is dominated by the electrostatic attraction between the electropositive σ-hole at the halogen atom X and the electronegative donor D. It has also been well-recognized that the CT from the donor D to the antibonding σ*(X-A) would weaken and lengthen the X-A bond. Yet, intriguingly, there is a blue-shifting phenomenon in halogen bonding, where the X-A bond contracts with an enhanced stretching vibrational frequency. Here we explored the nature of blue-shifting halogen bonds with the iconic case of H3N···ClNO2, which exhibits the blue-shifting phenomenon along with a strong CT interaction and its analogous H3N···XNY2 (X = Cl, Br, and I; Y = O, S). By decomposing the binding energy to a number of energy components and exploring their energy profiles along with the halogen-bonding distances with the block-localized wave function (BLW) method, we showed that the classical electrostatic interaction is the governing factor for the blue-shifting of the X-N bonds. This is further supported by the similar magnitudes of blue-shifting obtained when NH3 is replaced with atomic point charges in the complexes. Alternatively, by applying external electric field (E-field) along the X-N bond direction, the blue-to-red shifting transition can be identified. This is because both polarization and CT interactions tend to stretch the X-N bond, and both are enhanced simultaneously under the external E-field. Finally, roles of individual energy components are reconfirmed using the force analysis based on the BLW energy decomposition approach.

Tetrel bonding interaction: an analysis with the block-localized wavefunction (BLW) approach.

In this study, fifty-one iconic tetrel bonding complexes were studied using the block localized wave function (BLW) method which can derive the self-consistent wavefunction for an electron-localized (diabatic) state where charge transfer is strictly deactivated. Energy decompositions based on the BLW method (BLW-ED in short) show that the frozen energy, which is mostly composed of the Pauli repulsion and electrostatic components, plays the dominating role in thirty-one out of these fifty-one systems. A further quantitative study of electrostatic potential (ESP) was carried out by analyzing the variation of ESP along the binding direction for each monomer. In general, a Lewis base with the stronger ESP leads to higher stabilizing frozen and polarization energies. In addition, the relative strengths for complexes constructed with different carbon group elements are also examined qualitatively using the ESP model. The positive contribution of the charge transfer interaction is confirmed by both the BLW-ED results and the weakening of bond strengths after the charge transfer interaction is disabled. Finally, by replacing all atoms of a monomer with σ-holes (Lewis acid) with empirical point charges, attractive electrostatic interaction was observed in all cases, providing us a simple electrostatic explanation for the tetrel bonding, though the anisotropy of electron density associated with the σ-holes is unconsidered.

Atmospheric Chemistry of Enols: Vinyl Alcohol + OH + O2 Reaction Revisited.

The OH-initiated oxidation of vinyl alcohol (VA) produced by phototautomerization of acetaldehyde is thought to be a source of formic acid (FA) in the atmosphere. A recent theoretical study predicted that the VA + OH + O2 reaction 1 proceeds by OH addition at α-C (66%) and ß-C (33%) of VA and that FA is a main product of reaction 1. However, the metastable reactant ( anti-VA, ∼18% at 298 K, 1.42 kcal mol-1 higher than syn in energy) used in that study inspired us to reinvestigate reaction 1. Using the state-of-the-art quantum-chemical and kinetic calculations, we first found that a conformer of VA has a significant influence on the rate coefficient and branching ratio of reaction 1. Upon derivation, it is found that ∼84% of reaction 1 takes place through the ß-C-addition channel and ∼16% of reaction 1 happens by the α-C-addition channel. The calculated total initial rate coefficient at 298 K is 1.48 × 10-11 cm3 molecule-1 s-1, which is in reasonable agreement with the experimental values of similar systems (vinyl ethers + OH reactions). The predicted main products of reaction 1 are glycolaldehyde and the HO2 radical, whereas FA is just a byproduct.

Hydrogen- and Halogen-Bonds between Ions of like Charges: Are They Anti-Electrostatic in Nature?

Recent theoretical studies suggested that hydrogen bonds between ions of like charges are of a covalent nature due to the dominating nD →σ*H-A charge-transfer (CT) interaction. In this work, energy profiles of typical hydrogen (H) and halogen (X) bonding systems formed from ions of like charges are explored using the block-localized wavefunction (BLW) method, which can derive optimal geometries and wave functions with the CT interaction "turned off." The results demonstrate that the kinetic stability, albeit reduced, is maintained for most investigated systems even after the intermolecular CT interaction is quenched. Further energy decomposition analyses based on the BLW method reveal that, despite a net repulsive Coulomb repulsion, a stabilizing component exists due to the polarization effect that plays significant role in the kinetic stability of all systems. Moreover, the fingerprints of the augmented electrostatic interaction due to polarization are apparent in the variation patterns of the electron density. All in all, much like in standard H- and X-bonds, the stability of such bonds between ions of like charges is governed by the competition between the stabilizing electrostatic and charge transfer interactions and the destabilizing deformation energy and Pauli exchange repulsion. While in most cases of "anti-electrostatic" bonds the CT interaction is of a secondary importance, we also find cases where CT is decisive. As such, this work validates the existence of anti-electrostatic H- and X-bonds. © 2017 Wiley Periodicals, Inc.

Taxol Analogues Exhibit Differential Effects on Photoaffinity Labeling of ß-Tubulin and the Multidrug Resistance Associated P-Glycoprotein.

Several next-generation taxanes have been reported to possess high potency against Taxol-resistant cancer cell lines overexpressing ßIII-tubulin and/or P-glycoprotein (P-gp), both of which are involved in drug resistance. Using a photoaffinity Taxol analogue, 2-( m-azidobenzoyl)taxol, two potent next-generation taxanes, SB-T-1214 and SB-CST-10202, exhibited distinct inhibitory effects on photolabeling of ß-tubulin from different eukaryotic sources that differ in ß-tubulin isotype composition. They also specifically inhibited photolabeling of P-gp, and the inhibitory effect correlated well with the steady-state accumulation of [3H]vinblastine in a multidrug resistant (MDR) cell line, SKVLB1. Several microtubule-stabilizing agents (MSAs)-resistant cell lines from the human ovarian cancer cell line Hey were isolated, and their MDR1 and ßIII-tubulin levels determined. Distinct potencies of the two taxanes against different MSA-resistant cells expressing unique levels of MDR1 and ßIII-tubulin were found. Cytotoxicity assays, done in the presence of verapamil, indicated that SB-T-1214 is a substrate, although not as good as Taxol, for P-gp. The mechanisms involved in drug resistance are multifactorial, and the effectiveness of new Taxol analogues depends on the interaction between the drugs and all possible targets; in this case the two major cellular targets are ß-tubulin and P-gp.