Experimental evidence on the chemisorption bond of two- and one-dimensional boundaries

This paper is intended to provide an experimentalist's contribution to a critical discussion of adsorption energies and their significance. The experimental requirements, with special reference to the limitations and the quality of the information provided by the various techniques are briefly reviewed. The significance of the measurements, and the background theoretical (phenomenological and model) schemes which experimentalists use for interpreting their results, are discussed in order to show that the interpretations of surface measurements must be carefully analyzed by theoreticians intending to contribute to an understanding of surface bonding.     

On the interplay between theory and experiment in molecular structure problems: Some case studies

Some brief, general comments on the concept of molecular structure will be given. Some important points connected to the use of models in the interpretation of molecular structures will also be mentioned. The main theme in one part of the presentation will be the cooperative efforts made by experimentalists (mainly spectroscopists) and theoreticians (computational chemists) in order to measure, predict, and analyze the perturbations on the cyclopropane ring by different substituents. The aim is to demonstrate that ab initio calculations of a certain quality can constitute an important support for experimental studies in that they are able to discriminate between different models that otherwise are equally probable. The second part of the presentation will be concerned with a class of molecules that gives both experimental structural chemists and computational chemists a great challenge, namely, the metallocenes. A discussion of some of the grave discrepancies between theory and experiment regarding their geometry will be given.     

Strangely attractive: Collaboration and feedback in the field of molecular magnetism

The fluid synergy between experimentalists and theoreticians has, for decades, led to a deeper understanding of the processes that govern single-molecule magnets. This approach has allowed for the establishment of proven design criteria for the control of magnetic properties through molecular architecture and the development of new magnetic measurement techniques and innovative computational methodologies. Here, we give an account of the experimental and theoretical joint endeavor carried out as part of the synthesis group led by David Mills and the computational/theoretical team led by Nicholas Chilton, together with colleagues in synthetic f-element chemistry and magnetism at the University of Manchester. In addition, we provide a personal perspective on collaborative work in molecular magnetism and how such collaborations are essential for advancing the field further.     

DFT Study of Solvent Effects for Some Organic Molecules Using a Polarizable Continuum Model

Forty ionic molecules are studied by DFT (B3LYP, B3P86), MP4 with different basis sets using the PCM/UAHF model within the self-consistent reaction-field method to assess solvent effects. For these molecules, the solvation free energies (ΔG _sol) in water and the dipole moments in vacuoas well as in water are obtained. By comparing the calculated values of ΔG _sol with experimental values and molecular simulation results, it is found that the ΔG _sol values generated by the DFT method are in better agreement with experimental values. Moreover, especially for the B3LYP/6-31+G_∗ level, the results of both ΔG _sol and dipole moments are more accurate considering the lower computational cost. It can be noted that the dipole moments of solutes in water show some increase relative to those in vacuo.     

A Cationic Phosphapyramidane

Pyramidanes C[C₄R₄] constitute a novel class of highly strained and reactive polyhedral clusters that attracted a great deal of attention of both theoreticians and experimentalists. Although well‐studied from the theoretical viewpoint, pyramidanes were synthetically inaccessible, and only very recently their very first isolable representatives have been described. In this Communication, we report on the synthesis and structural studies of the cationic pyramidane with the Group 15 element at the apex, namely, phosphapyramidane, an isoelectronic analogue of the neutral pyramidanes of the Group 14 elements.     

Internal dynamics of simple floppy molecules

The dynamical behavior of simple nonrigid molecules still attracts much interest both from experimentalists and theoreticians. On the one hand, modern laser-spectroscopic techniques like SEP allow for the detection of highly excited vibrational–rotational states of a molecule, and advanced theoretical methods, on the other hand, are more and more able to calculate accurate potential energy surfaces and to simulate the intramolecular dynamics. The aim of the present article was to contribute to the understanding of the dynamical properties of simple floppy molecules by means of a comparative study of the two triatomics HCN and HO₂. Continuing our earlier work, we start from an analysis of the potential energy surface topography, then we investigate the classical dynamical behavior and the localization of the quantum states. Several conclusions of probably more general validity are drawn. © 1994 John Wiley & Sons, Inc.     

Two Types of Uncertainty in the Values of Activation Energy

The activation energies of the same process are often reported to have different values, which are usually explained by the differences in experimental conditions and sample characteristics. In addition to this type of uncertainty, which is associated with the process (ΔE _process) there is an uncertainty related to the method of computation of the activation energy (ΔE _method). For a method that uses fitting single heating rate data to various reaction models, the value of ΔE _method) method is large enough to explain significant differences in the reported values of the activation energy. This uncertainty is significantly reduced by using multiple heating rate isoconversional methods, which may be recommended for obtaining reference values for the activation energy. This revised version was published online in July 2006 with corrections to the Cover Date.     

Dissociation kinetics of singly protonated leucine enkephalin investigated by time-resolved photodissociation tandem mass spectrometry

The yields of post-source decay (PSD) and time-resolved photodissociation (PD) at 193 and 266 nm were measured for singly protonated leucine enkephalin ([YGGFL + H]⁺), a benchmark in the study of peptide ion dissociation, by using tandem time-of-flight mass spectrometry. The peptide ion was generated by matrix-assisted laser desorption ionization (MALDI) using 2,5-dihydroxybenzoic acid as the matrix. The critical energy (E₀) and entropy (ΔS‡ at 1000 K) for the dissociation were determined by Rice-Ramsperger-Kassel-Marcus fit of the experimental data. MALDI was done for a mixture of YGGFL and Y₆ and the plume temperature determined by the kinetic analysis of [Y₆ + H]⁺ data were used to improve the precision of E₀ and ΔS‡ for [YGGFL + H]⁺. E₀ and ΔS‡ thus determined (E₀ = 0.67 ± 0.08 eV, ΔS‡=−24.4 ± 3.2 eu with 1 eu = 4.184 J K⁻¹mol⁻¹) were significantly different from those determined by blackbody infrared radiative dissociation (BIRD) (E₀ = 1.10 eV, ΔS‡ = −14.9 eu), and by surface-induced dissociation (SID) (E₀ = 1.13 eV, ΔS‡ = −10.3 eu). Analysis of the present experimental data with the SID kinetics (and BIRD kinetics also) led to an unrealistic situation where not only PSD and PD but also MALDI-TOF signals could not be detected. As an explanation for the discrepancy, it was suggested that transition-state switching occurs from an energy bottleneck (SID/BIRD) to an entropy bottleneck (PSD/PD) as the internal energy increases.     

A short review and an empirical method for estimating the absorbed enthalpy of formation and the absolute enthalpy of dried microbial biomass for use in studies on the thermodynamics of microbial growth

Calculations are made using the equations Δ_r G = Δ_r H − TΔ_r S and Δ_r X = Δ_r H − Δ_r Q where Δ_r X represents the free energy change when the exchange of absorbed thermal energy with the environment is represented by Δ_r Q. The symbol Q has traditionally represented absorbed heat. However, here it is used specifically to represent the enthalpy listed in tabulations of thermodynamic properties as (H _T  − H ₀) at T = 298.15 K, the reason being that for a given substance TS equals 2.0 Q for solid substances, with the difference being greater for liquids, and especially gases. Since Δ_r H can be measured, and is tangibly the same no matter what thermodynamics are used to describe a reaction equation, a change in the absorbed heat of a biochemical growth process system as represented by either Δ_r Q or TΔ_r S would be expected to result in a different calculated value for the free energy change. Calculations of changes in thermodynamic properties are made which accompany anabolism; the formation of anabolic, organic by-products; catabolism; metabolism; and their respective non-conservative reactions; for the growth of Saccharomyces cerevisiae using four growth process systems. The result is that there is only about a 1% difference in the average quantity of free energy conserved during growth using either Eq. 1 or 2. This is because although values of TΔ_r S and Δ_r Q can be markedly different when compared to one another, these differences are small when compared to the value for Δ_r G or Δ_r X.     

A statistical model for the optimization of dsc performance in the evaluation of drugs for preformulation studies

Differential scanning calorimetry (DSC) is a thermal analytical tool for preformulation studies. Extrapolated melting temperature (T_P) and heat of fusion (ΔH_f) can be used as parameters for optimizing the DSC performance. Two model pharmaceuticals acetaminophen and nicotinamide are used in this study. Using a factorial design for the experimental model and matrix analysis the results, the effect of sample mass, heating rate and the nitrogen flow rate were evaluated on the ΔH_f values and T_P values. Two levels for each of the procedural variables were used as a balanced experimental design with two sample sizes, two heating rates and two nitrogen flow rates. It was found that the change in the heating rate caused significant changes in the ΔH_f values but not the T_p values for acetaminophen. However, no significant effect was found for the T_p value but ΔH_f value was affected to a certain extent for nicotinamide.     

Dependence of the energy of surface-active substances/metal interaction on their ionization potentials. Evaluation of hydrophilicity of metal

The function Δ(ΔG _A ⁰), which is the difference of Gibbs energies characterizing surface-active substance (surfactant, SAS) adsorption at metal/solution and air/solution surfaces, has been introduced. The equation connecting the function Δ(ΔG _A ⁰) with SAS ionization potential has been obtained using the elementary theory of donor-acceptor interactions. Published experimental data on SAS adsorption at mercury, bismuth and gold have been used for Δ(ΔG _A ⁰) calculation. The dependence of Δ(ΔG _A ⁰) on ionization potentials can be described by an equation derived in this work. It has been demonstrated that the value of the hydrophilicity of gold is much higher than the values for mercury and bismuth. The lifetime of SAS molecules at a metal surface has been estimated. The question of the possibility of theoretica l estimation of standard energies ΔG _A ⁰ characterizing SAS adsorption at a metal/solution surface has been discussed. Received: 9 December 1996 / Accepted: 13 January 1997     

Reply to the Comment on “Realization of Lewis Basic Sodium Anion in the NaBH3− Cluster”

We reply to the comment by S. Pan and G. Frenking who challenged our interpretation of the Na⁻:→BH₃ dative bond in the recently synthesized NaBH₃⁻ cluster. Our conclusion remains the same as that in our original paper ( https://doi.org/10.1002/anie.201907089 and https://doi.org/10.1002/ange.201907089 ). This conclusion is additionally supported by the energetic pathways and NBO charges calculated at UCCSD and CASMP2(4,4) levels of theory. We also discussed the suitability of the Laplacian of electron density (QTAIM) and Adaptive Natural Density Partitioning (AdNDP) method for bond type assignment. It seems that AdNDP yields more sensible results. This discussion reveals that the complex realm of bonding is full of semantic inconsistencies, and we invite experimentalists and theoreticians to elaborate this topic and find solutions incorporating different views on the dative bond.     

Reply to the Comment on “Realization of Lewis Basic Sodium Anion in the NaBH3− Cluster”

We reply to the comment by S. Pan and G. Frenking who challenged our interpretation of the Na^?:→BH₃ dative bond in the recently synthesized NaBH₃^? cluster. Our conclusion remains the same as that in our original paper ( https://doi.org/10.1002/anie.201907089 and https://doi.org/10.1002/ange.201907089 ). This conclusion is additionally supported by the energetic pathways and NBO charges calculated at UCCSD and CASMP2(4,4) levels of theory. We also discussed the suitability of the Laplacian of electron density (QTAIM) and Adaptive Natural Density Partitioning (AdNDP) method for bond type assignment. It seems that AdNDP yields more sensible results. This discussion reveals that the complex realm of bonding is full of semantic inconsistencies, and we invite experimentalists and theoreticians to elaborate this topic and find solutions incorporating different views on the dative bond.     

Benchmarking of density functionals for a soft but accurate prediction and assignment of 1H and 13C NMR chemical shifts in organic and biological molecules

A number of programs and tools that simulate ¹H and ¹³C nuclear magnetic resonance (NMR) chemical shifts using empirical approaches are available. These tools are user‐friendly, but they provide a very rough (and sometimes misleading) estimation of the NMR properties, especially for complex systems. Rigorous and reliable ways to predict and interpret NMR properties of simple and complex systems are available in many popular computational program packages. Nevertheless, experimentalists keep relying on these “unreliable” tools in their daily work because, to have a sufficiently high accuracy, these rigorous quantum mechanical methods need high levels of theory. An alternative, efficient, semi‐empirical approach has been proposed by Bally, Rablen, Tantillo, and coworkers. This idea consists of creating linear calibrations models, on the basis of the application of different combinations of functionals and basis sets. Following this approach, the predictive capability of a wider range of popular functionals was systematically investigated and tested. The NMR chemical shifts were computed in solvated phase at density functional theory level, using 30 different functionals coupled with three different triple–ζ basis sets. © 2016 Wiley Periodicals, Inc.     

Enabling drug discovery project decisions with integrated computational chemistry and informatics

Computational chemistry/informatics scientists and software engineers in Genentech Small Molecule Drug Discovery collaborate with experimental scientists in a therapeutic project-centric environment. Our mission is to enable and improve pre-clinical drug discovery design and decisions. Our goal is to deliver timely data, analysis, and modeling to our therapeutic project teams using best-in-class software tools. We describe our strategy, the organization of our group, and our approaches to reach this goal. We conclude with a summary of the interdisciplinary skills required for computational scientists and recommendations for their training.     

Empirical estimation of the energetic contribution of individual interface residues in structures of protein–protein complexes

We report a simple algorithm to scan interfaces in protein–protein complexes for identifying binding ‘hot spots’. The change in side-chain solvent accessible area (ΔASA) of interface residues has been related to change in binding energy due to mutating interface residues to Ala (ΔΔG _X → ALA) based on two criteria—hydrogen bonding across the interface and location in the interface core—both of which are major determinants in specific, high-affinity binding. These relationships are used to predict the energetic contribution of individual interface residues. The predictions are tested against 462 experimental X → ALA mutations from 28 interfaces with an average unsigned error of 1.04 kcal/mol. More than 80% of interface hot spots (with experimental ΔΔG ≥ 2 kcal/mol) could be identified as being energetically important. From the experimental values, Asp, Lys, Tyr and Trp are found to contribute most of the binding energy, burying >45 Å² on average. The method described here would be useful to understand and interfere with protein interactions by assessing the energetic importance of individual interface residues. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Estimation of gas-phase acidities of deoxyribonucleosides: An experimental and theoretical study

We determined the gas-phase acidities (ΔH_acid) of four deoxyribonucleosides, i.e., 2′-deoxyadenosine (dA), 2′-deoxyguanosine (dG), 2′-deoxycytidine (dC), and 2′-deoxythymidine (dT) by applying the extended kinetic method. The negatively charged proton-bound hetero-dimeric anions, [A-H-B]⁻ of the deoxyribonucleosides (A) and reference compounds (B) were generated under electrospray ionization conditions. Collision-induced dissociation spectra of [A-H-B]⁻ were recorded at four different collision energies using a triple quadrupole mass spectrometer. The abundance ratios of the individual monomeric product ions were used to determine the ΔH_acid of the deoxyribonucleosides. The obtained ΔH_acid value follows the order dA7>dC7>dT7>dG. The ΔG_acid (298 K) values were determined by using ΔG_acid=ΔH_acid-TΔS_acid where the ΔH_acid and ΔS_acid values were determined directly from the kinetic method plots. The ΔH_acid values were also predicted for the deoxyribonucleosides at the B3LYP/6-311+G**//B3LYP/6-311G** level of theory. The acidity trend obtained from the computational investigation shows good agreement with that obtained experimentally by the extended kinetic method. Theoretical calculations provided the most preferred deprotonation site as C5′-OH from sugar moiety in case of dA, and as −NH₂ (dC and dG) or -NH- (dT) from nitrogenous base moiety in the case of other deoxyribonucleosides.