Pyridoxal reactions with amines and aliphatic diamines

Interaction of pyridoxal (3-hydroxy-5-hydroxymethyl-2-methylisonicotinaldehyde) with amines, mono- and disubstituted diamines led to the formation of compounds having in their structure imine, imidazolidine, and pyrimidine moieties. Structure of the obtained compounds was proved by IR data, ¹H NMR spectroscopy, mass spectrometry, and X-ray diffraction analysis.     

Prediction of pKa shifts in proteins using a combination of molecular mechanical and continuum solvent calculations

The prediction of pKa shifts of ionizable groups in proteins is of great relevance for a number of important biological phenomena. We present an implementation of the MM-GBSA approach, which combines molecular mechanical (MM) and generalized Born (GB) continuum solvent energy terms, to the calculation of pKa values of a panel of nine proteins, including 69 individual comparisons with experiment. While applied so far mainly to the calculation of biomolecular binding free energies, we show that this method can also be used for the estimation of protein pKa shifts, with an accuracy around 1 pKa unit, even for strongly shifted residues. Our analysis reveals that the nonelectrostatic terms that are part of the MM-GBSA free energy expression are important contributors to improved prediction accuracy. This suggests that most of the previous approaches that focus only on electrostatic interactions could be improved by adding other nonpolar energy terms to their free energy expression. Interestingly, our method yields best accuracy at protein dielectric constants of epsilonint = 2-4, which is in contrast to previous approaches that peak at higher epsilonint > or = 8. An important component of our procedure is an intermediate minimization step of each protonation state involving different rotamers and tautomers as a way to explicitly model protein relaxation upon (de)protonation.     

Polarizable continuum model with the fragment molecular orbital-based time-dependent density functional theory

The polarizable continuum model (PCM) for describing the solvent effect was combined with the fragment molecular orbital-based time-dependent density functional theory (TDDFT). Several levels of the many-body expansion were implemented, and the importance of the many-body contributions to the singlet-excited states was discussed. To calibrate the accuracy, we performed a number of the model calculations using our method and the regular TDDFT in solution, applying them to phenol and polypeptides at the long-range corrected BLYP/6-31G* level. It was found that for systems up to 192 atoms the largest error in the excitation energy was 0.006 eV (vs. the regular TDDFT/PCM of the full system). The solvent shifts and the conformer effects were discussed, and the scaling was found to be nearly linear. Finally, we applied our method to the lowest singlet excitation of the photoactive yellow protein (PYP) in aqueous solution and determined the excitation energy to be in reasonable agreement with experiment. The excitation energy analysis provided the contributions of individual residues, and the main factors as well as their solvent shifts were determined.     

A state-specific polarizable continuum model time dependent density functional theory method for excited state calculations in solution

An effective state specific (SS) model for the inclusion of solvent effects in time dependent density functional theory (TD-DFT) computations of excited electronic states has been developed and coded in the framework of the so-called polarizable continuum model (PCM). Different relaxation time regimes can be treated thus giving access to a number of different spectroscopic properties together with solvent relaxation energies of paramount relevance in electron transfer processes. SS and conventional linear response (LR) models have been compared for two benchmark systems (coumarin 153 and formaldehyde in different solvents) and in the limiting simple case of a dipolar solute embedded in a spherical cavity. The results point out the complementarity of LR and SS approaches and the advantages of the latter model especially for polar solvents. The favorable scaling properties of PCM-TD-DFT models in both SS and LR variants and their availability in effective quantum mechanical codes pave the route for the computation of reliable spectroscopic properties of large molecules of technological and/or biological interest in their natural environments.     

Chemosensor for the optical detection of aliphatic amines and diamines

Two new chemosensor dyes with either one or two trifluoroacetophenone recognition moieties have been investigated in terms of reversibly interacting with amines and diamines.     

Prediction of pKa values of nido-carboranes by density functional theory methods

A great parallel exists between metal complexes of cyclopentadienyl and arene ligands on one side and metal complexes of the nido derivatives of the icosahedral o-carborane clusters. With few exceptions, the metal complexation in the cluster can be viewed as the substitution of one or more bridging hydrogen atoms by the metal. Therefore, a necessary requirement for the complexation is the deprotonation of the nido cluster to generate a coordination site for that metal. The reaction to remove these protons, which most probably is one of the most commonly done processes in boron and metallaborane chemistry, is barely known, and no quantitative data are available on the magnitude of their pKa values. With the purpose of determining the acidity of nido-carboranes, a procedure to calculate the pKa values of nido boron clusters is presented in this paper for the first time. To this objective, some nido clusters have been selected and their geometry and NMR-spectroscopic properties have been studied, giving a good correlation between the theoretical and experimental data in both geometry distances and 11B NMR spectroscopy. Of notice is the result that proves that the singular carbon atom in the thermodynamic isomer of [C2B10H13]- is definitely part of the cluster and that its connection with the C2B3 face would be better defined by adding additional interactions with the two boron atoms nearest to the second cluster carbon. The pKa values of the nido species have been calculated by correlating experimental pK(a) values and calculated reaction Gibbs energies DeltaG(s). Some pKa values of importance are -4.6 and +13.5 for 7,8-[C2B9H13] (1) and 7,8-[C2B9H12]- (2), respectively.     

Modeling ultrafast solvated electronic dynamics using time-dependent density functional theory and polarizable continuum model

A first-principles solvated electronic dynamics method is introduced. Solvent electronic degrees of freedom are coupled to the time-dependent electronic density of a solute molecule by means of the implicit reaction field method, and the entire electronic system is propagated in time. This real-time time-dependent approach, incorporating the polarizable continuum solvation model, is shown to be very effective in describing the dynamical solvation effect in the charge transfer process and yields a consistent absorption spectrum in comparison to the conventional linear response results in solution.     

Protonated primary amines induced thymine quintets studied by electrospray ionization mass spectrometry and density functional theory calculations

As the novel magic number clusters of nucleobases, the thymine quintets induced by ammonium ion (NH₄⁺), and particularly by its derivatives such as protonated alkyl amines and protonated aryl amines, have been studied by electrospray ionization mass spectrometry (ESI‐MS) and density functional theory (DFT) calculations. The DFT‐optimized geometry of NH₄⁺ induced thymine quintet ([T₅ + NH₄]⁺) reveals some new features including three additional hydrogen bonds between NH₄⁺ and its surrounding thymine molecules when compared with that of the alkali metal ions induced thymine quintets. In addition, the fourth hydrogen atom of NH₄⁺ is sticking out the assembly, and, thus, it might be replaced by an organic group R to form the protonated primary amine induced thymine quintet ([T₅ + R ? NH₃]⁺), a hypothesis that has been confirmed by both DFT calculations and ESI‐MS experiments. Furthermore, the relative abilities of the different protonated primary amines for inducing the thymine quintets are investigated by ESI‐MS competition experiments, and the results have shown a clear trend of stronger ability as the alkyl chain gets longer or as the aryl ring gets larger for the alkyl amines or the aryl amines. Two basic influence factors are consequently identified: one is the ability of the alkyl amine to accept proton, another is the π–π stacking interaction between the aryl ring and the π‐surface of the thymine molecule(s), whose explanations are strongly supported by multiple types of thermochemical data, various control experiments and DFT calculations. Copyright © 2014 John Wiley & Sons, Ltd.     

A density functional theory formulation of the reaction field model of solvent effects

It is possible to reformulate the reaction field (RF ) model of continuum solvent effects, by considering an approximate expression describing the energy changes from one ground state to another, in the frame of density functional theory (DFT ). The energy functional for an arbitrary electronic system coupled to a spin-independent electrostatic external perturbation is used to derive the well-known Born expression giving the electrostatic component of the solvation energy of an atomic ion. The approximate RF –DFT model is illustrated for a series of representative singly positive and negatively charged atomic ions. A Kohn–Sham (KS )-like formalism is then proposed to compute solvation energies within a self-consistent field scheme. The extension of the RF -DFT model to molecular systems is also outlined. © 1995 John Wiley & Sons, Inc.     

Microdetermination and pKa measurement of some aliphatic amines using the copper-ion-selective electrode

Aliphatic amines were determined on the microscale by potentiometric titration with standard cupric sulfate solution in aqueous or partially aqueous (methanolic) medium. Electromotive forces were monitored with a copper-ion-selective electrode or a graphite rod impregnated with silver sulfide/cupric sulfide, and a double-junction reference electrode. Monoamines and diamines up to 1,3-diaminopropane reacted on a 2:1 amine:Cu basis. Diamines from 1,4-diaminobutane to at least 1,7-diaminoheptane reacted on an equimolar basis. The dissociation constants of some of the amines were determined. A linear relationship exists between the emf at half complexation and the dissociation constants of the amines tested.     

A dynamic density functional theory for particles in a flowing solvent

We present a dynamic density functional theory (dDFT) which takes into account the advection of the particles by a flowing solvent. For potential flows, we can use the same closure as in the absence of solvent flow. The structure of the resulting advected dDFT suggests that it could be used for nonpotential flows as well. We apply this dDFT to Brownian particles (e.g., polymer coils) in a solvent flowing around a spherical obstacle (e.g., a colloid) and compare the results with direct simulations of the underlying Brownian dynamics. Although numerical limitations do not allow for an accurate quantitative check of the advected dDFT both show the same qualitative features. In contrast to previous works which neglected the deformation of the flow by the obstacle, we find that the bow wave in the density distribution of particles in front of the obstacle as well as the wake behind it are reduced dramatically. As a consequence, the friction force exerted by the (polymer) particles on the colloid can be reduced drastically.     

Recent applications of density functional theory calculations to biomolecules

The purpose of this overview is to highlight the broad scope and utility of current applications of density functional theory (DFT) methods for the study of the properties and reactions of biomolecules. This is illustrated using examples selected from research carried out within our research group and in collaboration with others. The examples include the hyperfine coupling constants of amino acid radicals, the use of an amino acid as a chiral catalyst for the formation of carbon–carbon bonds in the aldol reaction, hydrogen-bond mediated catalysis of an aminolysis reaction, radiation-induced protein–DNA cross-links, and the mechanism by which an antitumor drug cleaves DNA. We demonstrate that DFT-based methods can be applied successfully to a broad range of problems that remain beyond the scope of conventional electron-correlation methods. Furthermore, we show that contemporary computational quantum chemistry complements experiment in the study of biological systems. Received: 19 December 2001 / Accepted: 8 April 2002 / Published online: 4 July 2002     

Methylation of zebularine investigated using density functional theory calculations

Deoxyribonucleic acid (DNA) methylation is an epigenetic phenomenon, which adds methyl groups into DNA. This study reveals methylation of a nucleoside antibiotic drug 1‐(β‐D ‐ribofuranosyl)‐2‐pyrimidinone (zebularine or zeb) with respect to its methylated analog, 1‐(β‐D ‐ribofuranosyl)‐5‐methyl‐2‐pyrimidinone (d5) using density functional theory calculations in valence electronic space. Very similar infrared spectra suggest that zeb and d5 do not differ by types of the chemical bonds, but distinctly different Raman spectra of the nucleoside pair reveal that the impact caused by methylation of zeb can be significant. Further valence orbital‐based information details on valence electronic structural changes caused by methylation of zebularine. Frontier orbitals in momentum space and position space of the molecules respond differently to methylation. Based on the additional methyl electron density concentration in d5, orbitals affected by the methyl moiety are classified into primary and secondary contributors. Primary methyl contributions include MO8 (57a), MO18 (47a), and MO37 (28a) of d5, which concentrates on methyl and the base moieties, suggest certain connection to their Frontier orbitals. The primary and secondary methyl affected orbitals provide useful information on chemical bonding mechanism of the methylation in zebularine. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Studies of iridium nanoparticles using density functional theory calculations

The energetics and the electronic and magnetic properties of iridium nanoparticles in the range of 2-64 atoms were investigated using density functional theory calculations. A variety of different geometric configurations were studied, including planar, three-dimensional, nanowire, and single-walled nanotube. The binding energy per atom increases with size and dimensionality from 2.53 eV/atom for the iridium dimer to 6.09 eV/atom for the 64-atom cluster. The most stable geometry is planar until four atoms are reached and three-dimensional thereafter. The simple cubic structure is the most stable geometric building block until a strikingly large 48-atom cluster, when the most stable geometry transitions to face-centered cubic, as found in the bulk metal. The strong preference for cubic structure among small clusters demonstrates their rigidity. This result indicates that iridium nanoparticles intrinsically do not favor the coalescence process. Nanowires formed from linear atomic chains of up to 4-atom rings were studied, and the wires formed from 4-atom rings were extremely stable. Single-walled nanotubes were also studied. These nanotubes were formed by stacking 5- and 6-atom rings to form a tube. The ring stacking with each atom directly above the previous atom is more stable than if the alternate rings are rotated.     

Quantum chemical calculations for the hydration of model silica modified by aliphatic amines

Various basis sets and methods for quantum-chemical calculations are analyzed, and the effect of the number of diffusion and polarization functions on geometry and energy characteristics of systems that simulate the surface of silica modified by aliphatic amines is studied. The contribution from correlation effects and the superposition error of the basis set to the values of the energy characteristics of the hydration of model objects is evaluated. A section of an aminosilica surface was hydrated in simulation. Conclusions as to the existence of arched structures on the surface of aminosilica that include amino and silanol groups are confirmed.     

Theoretical Auger electron spectra of polymers by density functional theory calculations using model dimers

We propose a new approach for analysis of Auger electron spectra (AES) of polymers by density functional theory (DFT) calculations with the Slater's transition-state concept. Simulated AES and X-ray photoelectron spectra (XPS) of four polymers [(CH2CH2)n (PE), (CH2CH(CH3))n (PP), (CH2CH(OCH3))n (PVME), and (CH2CH(COCH3))n (PVMK)] by DFT calculations using model dimers are in a good accordance with the experimental ones. The experimental AES of the polymers can be classified in each range of 1s-2p2p, 1s-2s2p, and 1s-2s2s transitions for C KVV and O KVV spectra, and in individual contributions of the functional groups from the theoretical analysis.     

Matrix infrared spectra and density functional theory calculations of molybdenum hydrides

Laser-ablated Mo atoms react with H2 upon condensation in excess argon, neon, and hydrogen. The molybdenum hydrides MoH, MoH2, MoH4, and MoH6 are identified by isotopic substitution (H2, D2, HD, H2 + D2) and by comparison with vibrational frequencies calculated by density functional theory. The MoH2 molecule is bent, MoH4 is tetrahedral, and MoH6 appears to have the distorted trigonal prism structure.     

Prediction of cellulose nanotube models through density functional theory calculations

We report the generation of a nano-scale tubular structure of cellulose molecules (CelNT), through density functional theory (DFT) calculations. When a cellulose III_I (1 0 0) chain sheet model is optimized by DFT calculations, the sheet models spontaneously roll into tubes. The oligomers arrange in a right-handed, four-fold helix with one-quarter chain staggering, oriented with parallel polarity similar to the original crystal structure. Based on a one-quarter chain staggering relationship, six large CelNT models, consisting of 16 cellulose chains with DP = 80, are constructed by combinations of two types of chain polarities and three types of symmetry operations to generate a circular arrangement of molecular chains. All six CelNT models are examined by molecular dynamics (MD) calculations in chloroform. While four CelNT models retain a tubular form throughout MD calculations, the remaining two deform. 3D-RISM theory model is used to estimate the solvation free energies of the four CelNT models. The results suggest that the CelNT model with a chain arrangement of parallel polarity and right-handed helical symmetry forms the most stable tube structure.