Can cluster structure affect kinetic method measurements? The curious case of glutamic acid’s gas-phase acidity

The gas-phase acidities of aspartic, glutamic, and 2-aminoadipic acid have been determined by the kinetic method in a triple-quadrupole instrument. Although aspartic acid behaves in the conventional way and gives a DeltaH(acid) value of 1340 kJ mol(-1), glutamic and 2-aminoadipic acids give kinetic method plots with two distinct slopes. This leads to DeltaH(acid) values of 1350 and 1366 kJ mol(-1) for glutamic acid, and 1355 and 1369 kJ mol(-1) for 2-aminoadipic acid. The value for aspartic acid and the low collision energy value for glutamic acid are consistent with recent measurements by Poutsma and co-workers in a quadrupole ion trap. The experiments are supported by calculations at the G3(MP2) and OLYP/aug-cc-pVTZ levels. Computational studies of model clusters of the amino acids with trifluoroacetate suggest there are distinct preferences. Glutamic and 2-aminoadipic acid prefer clusters where the amino acid adopts a zwitterion-like structure whereas aspartic acid prefers to adopt a conventional (canonic) structure in its clusters. This result along with the computed stabilities of zwitterion-like conformations of the deprotonated amino acids leads to the following explanation for the presence of two slopes in the kinetic method plots. At low collision energies, the deprotonated amino acid dissociates from the cluster, with rearrangement if necessary, to give its preferred conformation, but at high collision energies, the deprotonated amino acid directly dissociates in the conformation preferred in the cluster. For glutamic and 2-aminoadipic acids, this is a zwitterion-like structure that is about 20 kJ mol(-1) less stable than the global minimum.     

Atom diffusion in furnaces — models and measurements

Experimental as well as the theoretical approach to estimate diffusion coefficients for several analyte elements with different behavior in graphite furnaces, lead, gold, indium and chromium, were investigated. ‘Close’ graphite furnaces of two designs differing in the size of end apertures and the diameter of the injection port were used. The furnaces were fast heated at rates of approximately 10 000 K s⁻¹. The peak absorbance of all studied analytes was independent of geometry, suggesting that the separation of atomization and removal was attained. Residence times of the analytes in the two different furnaces were determined from absorbance tail shapes. In the case of gold, the influence of temperature in the range between 1800 and 2200 K on the residence time in both furnaces was also found. The residence times measured in the two different furnaces under otherwise identical conditions, made possible to select the accurate model of diffusional removal from several possible models. The knowledge of the accurate model allowed the estimate of experimental diffusion coefficients. They were thus compared with those semiempirically calculated from kinetic theory of gases, extended to allow for the intermolecular forces. The accuracy of these calculations is limited since the input data (critical temperatures, boiling temperature or melting temperature, molal volumes at the critical, boiling and melting points, metallic crystallographic radii and dissociation constants of metal dimers) are not known with adequate accuracy. The comparison of ‘theoretical’ and ‘experimental’ values of diffusion coefficients makes possible to assess value of using individual sources of input data for the semiempirical calculations.     

The atomic force microscope: Can it be used to study biological molecules?

The conditions necessary for studying biological molecules with the atomic force microscope are discussed. It is shown that in order to avoid large substrate deformations the microscope should be operated in its attractive mode where the van der Waals force between the tip and the substrate is ≈ 10⁻¹¹ N and where the tip-substrate separation is of the order of 4–5 Å.     

Can we outperform the DIIS approach for electronic structure calculations?

This article regroups various results on self-consistent field algorithms for computing electronic structures of molecular systems. The first part deals with the convergence properties of the “conventional” Roothaan algorithm and of the level-shifting algorithm. In the second part, a new class of algorithms is introduced, for which convergence is guaranteed by mathematical arguments. Computational performance on various test problems is reported; advantages of this new approach are demonstrated. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 79: 82–90, 2000     

Can contact-angle measurements determine the disjoining pressure in liquid nanofilms on rigid substrates?

The disjoining pressure of lubricant nanofilms used in the magnetic recording industry controls the equilibrium wetting, the dynamics of film restoration, and the evaporation kinetics of the film. It has been claimed that by measuring the contact angle of nonpolar and polar liquids on lubricant films, the disjoining pressure can be extracted using the method of Girafalco and Good, and such analyses have appeared in the literature. The approximations underlying the method have been discussed before in the literature. In view of the importance of measuring disjoining pressure in nanofilms of lubricants, it is timely to revisit these assumptions to understand the validity of the contact-angle method presently in use. We re-derive the relevant equations using a thermodynamic-interaction-energy approach which is free of the problems inherent in the original derivation and make explicit the assumptions which must be made in the derivation. General interaction energy arguments are then invoked to demonstrate that it does not appear possible to obtain the disjoining pressure in the film from contact-angle measurements in an unambiguous manner.     

Can the ASTM heat distortion test provide more than just a single-point measurement?

It is shown that the single-point heat distortion temperature value obtained under ASTM D648-72 can be used as a normalizing factor to coalesce heat distortion temperature versus stress curves for a generic type of polymer. The advantage of such curves lies in their ability to provide a quick estimate of the behaviour of the materials at other stress levels useful for design purposes.     

What can time-resolved diffraction tell us about transient species?: excited-state structure determination at atomic resolution

The author describes his work for which he coined the word 'photocrystallography', a technique which consists of using a laser to pump, or excite, a molecular crystal while the X-ray diffractometer probes its structure at the atomic level. The technique is being used to study highly reactive excited molecules that exist for just millionths or even billionths of a second using very intense light sources at the National Synchrotron Light Source at Brookhaven National Laboratory and the Advanced Photon Source at Argonne National Laboratory.     

Why do molecules echo atomic periodicity?

Franck–Condon factors are investigated for sequences of free main‐group diatomic molecules. Theory‐based Condon loci (parabolas) and Morse‐potential loci are plotted on Deslandres tables to verify if they, indeed, follow the largest Franck–Condon factors. Then, the inclination angles of the Condon loci are determined. Thus, entire band systems are quantified by one variable, the angle. For all available isoelectronic sequences, this angle increases from a central minimum toward magic‐number molecular boundaries. The theory for the Condon locus gives the angle in terms of the ratio of the upper‐state to the lower‐state force constants. It is concluded that the periodicity is caused due to the fact that this ratio becomes larger as rare‐gas molecules are approached, a trend that probably points to the extreme cases of the rare‐gas molecules themselves. Thus, molecular periodicity echoes atomic periodicity in that data plots have extrema at molecules with magic‐number atoms, yet it does not echo the details of atomic periodicity in series between those molecules. © 2013 The Authors. International Journal of Quantum Chemistry Published by Wiley Periodicals, Inc.     

Expansion of potential 1/r12 of atomic systems in hyper-spherical harmonics

The expansion coefficient C[L]D of Coulomb potential 1/r12 ofatomic system in hyper-spherical harmonics is derived and the explicit expression is given.     

Charges fit to electrostatic potentials. II. Can atomic charges be unambiguously fit to electrostatic potentials?

The present work examines the conditioning of the least-squares matrix for obtaining potential derived charges and presents a modification of the CHELP method for fitting atomic charges to electrostatic potentials. Results from singular value decompositions (SVDs) of the least-squares matrices show that, in general, the least-squares matrix for this fitting problem will be rank deficient. Thus, statistically valid charges cannot be assigned to all the atoms in a given molecule. We find also that, contrary to popular notions, increasing the point density of the fit has little or no influence on the rank of the problem. Improvement in the rank can best be achieved by selecting points closer to the molecular surface. Basis set has, as expected, no effect on the number of charges that can be assigned. Finally, a well-defined, computationally efficient algorithm (CHELP-SVD) is presented for determining the rank of the least-squares matrix in potential-derived charge fitting schemes, selecting the appropriate subset of atoms to which charges can be assigned based on that rank estimate, and then refitting the selected set of charges. © 1996 by John Wiley & Sons, Inc.     

Can a physics‐based,all‐atom potential find a protein's native structure among misfolded structures? I. Large scale AMBER benchmarking

Recent work has shown that physics-based, all-atom energy functions (AMBER, CHARMM, OPLS-AA) and local minimization, when used in scoring, are able to discriminate among native and decoy structures. Yet, there have been only few instances reported of the successful use of physics based potentials in the actual refinement of protein models from a starting conformation to one that ends in structures, which are closer to the native state. An energy function that has a global minimum energy in the protein's native state and a good correlation between energy and native-likeness should be able to drive model structures closer to their native structure during a conformational search. Here, the possible reasons for the discrepancy between the scoring and refinement results for the case of AMBER potential are examined. When the conformational search via molecular dynamics is driven by the AMBER potential for a large set of 150 nonhomologous proteins and their associated decoys, often the native minimum does not appear to be the lowest free energy state. Ways of correcting the potential function in order to make it more suitable for protein model refinement are proposed.     

Are there atomic orbitals in a molecule?

Effective atomic orbitals (AOs) have been calculated by the method of the "fuzzy atoms" analysis by using the numerical molecular orbitals (MOs) obtained from plane-wave DFT calculation, i.e., without introducing any atom-centered functions. The results show that in the case of nonhypervalent atoms there are as many effective AOs with non-negligible occupation numbers, as many orbitals are in the classical minimal basis set of the given atom. This means that, for nonhypervalent systems, it is possible to present the MOs as sums of effective atomic orbitals that resemble very much the atomic minimal basis orbitals of the individual atoms (or their hybrids). For hypervalent atoms some additional orbitals basically of d-type are also of some importance; they are necessary to describe the back-donation to these positive atoms. It appears that the d-type orbitals play a similar role also for strongly positive carbon atoms. The method employed here is also useful to decide whether the use of polarization functions of a given type is a matter of conceptual importance or has only a numerical effect.     

Speciation in atomic spectrometry—an oxymoron?

Because atomic spectrometry inherently involves the decomposition of a sample into its constituent atoms, it inevitably destroys speciation information. Only by combining an atomic spectrometric method withan auxiliary, species-specific technique, or by modifying the ‘atomic’ spectrometer substantially, can speciation by ascertained. In this brief paper, three alternative approaches to speciation are outlined. Among them, the use of a switched or modulated source seems particularly appealing.     

Can an electron-shell closing model explain the structure and stability of ligand-stabilized metal clusters?

We investigated the structure and stability of several aluminum hydride complexes to understand the essence of "superatom chemistry" and to gain a right perspective on the ligand (L)-stabilized metal (M) clusters. We successfully interpret the structure and stability using molecular orbital analysis, which clearly shows the failure of an electron-shell closing model (or a superatom model) to explain it. The structure and stability of Al(m)H(n) are closely associated with the molecular orbital stabilization owing to the effective orbital overlap between Al(m) (M(m)) and nH (nL). The importance of retaining the electronic structural integrity of M(m) in M(m)L(n)-within an electron-shell closing model-has been underestimated or even disregarded, and this has created the current controversies in the scientific community.     

Molecular versus tissue liquids: an atomic length?

For the monatomic classical liquids like Ar, Kr and Xe, it has long been known that near the triple point, the product of surface tension σ and isothermal compressibility K_T , having dimensions of length, is less than 1?Å. More recently, a similar result has been established from experimental data on some 20 organic liquids. The purpose of this article is to raise a possibly interesting question with experimentalists working on complex molecular liquids as well as biological cell assemblies. Thus, we first draw attention to measurements of the compressibility of some 25 proteins in water. Can complementary measurements of surface tension be carried out on at least some of these systems? And is the product σK_T a length of order of an Å or so? Second, we note existing measurements of surface tension σ on five embryonic tissues and ask essentially the same question as to whether or not the product σK_T is of atomic dimensions. Finally, via a biopsy of a tumour which might provide material to yield an approximately spherical aggregate of the cancerous cells, is σK_T measurable and if so, is this product dependent on the presence of the tumour?     

Solvent reaction field potential inside an uncharged globular protein: a bridge between implicit and explicit solvent models?

The solvent reaction field potential of an uncharged protein immersed in simple point charge/extended explicit solvent was computed over a series of molecular dynamics trajectories, in total 1560 ns of simulation time. A finite, positive potential of 13-24 kbTec(-1) (where T=300 K), dependent on the geometry of the solvent-accessible surface, was observed inside the biomolecule. The primary contribution to this potential arose from a layer of positive charge density 1.0 A from the solute surface, on average 0.008 ec/A3, which we found to be the product of a highly ordered first solvation shell. Significant second solvation shell effects, including additional layers of charge density and a slight decrease in the short-range solvent-solvent interaction strength, were also observed. The impact of these findings on implicit solvent models was assessed by running similar explicit solvent simulations on the fully charged protein system. When the energy due to the solvent reaction field in the uncharged system is accounted for, correlation between per-atom electrostatic energies for the explicit solvent model and a simple implicit (Poisson) calculation is 0.97, and correlation between per-atom energies for the explicit solvent model and a previously published, optimized Poisson model is 0.99.     

In silico exploratory study using structure–activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay

The mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure–activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity in vitro based on the Ames test and in vivo based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity in vitro, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity in vivo, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals in vitro and in vivo.     

Can an in silico drug-target search method be used to probe potential mechanisms of medicinal plant ingredients?

Medicinal plants have been explored therapeutically in traditional medicines and are a valuable source for drug discovery. Insufficient knowledge about the molecular mechanism of these medicinal plants limits the scope of their application and hinders the effort to design new drugs using the therapeutic principles of herbal medicines. This problem can be partially alleviated if efficient methods for rapid identification of protein targets of herbal ingredients can be introduced. Efforts have been directed at developing efficient computer methods for facilitating target identification. Various methods being explored or under investigation are reviewed here. So far, one computer method, INVDOCK, has been specifically used for automated drug target identification. Its usefulness in the identification of therapeutic targets of medicinal herbal ingredients as well as synthetic chemicals is reviewed. The majority of INVDOCK identified therapeutic targets of several well-known medicinal herbal ingredients have been found to be confirmed or implicated by experiments, which suggests the potential of in silico methods in facilitating the study of molecular mechanism of medicinal plants.