DFT-based Green's function pathways model for prediction of bridge-mediated electronic coupling

A density functional theory-based Green's function pathway model is developed enabling further advancements towards the long-standing challenge of accurate yet inexpensive prediction of electron transfer rate. Electronic coupling predictions are demonstrated to within 0.1 eV of experiment for organic and biological systems of moderately large size, with modest computational expense. Benchmarking and comparisons are made across density functional type, basis set extent, and orbital localization scheme. The resulting framework is shown to be flexible and to offer quantitative prediction of both electronic coupling and tunneling pathways in covalently bound non-adiabatic donor–bridge–acceptor (D–B–A) systems. A new localized molecular orbital Green's function pathway method (LMO-GFM) adaptation enables intuitive understanding of electron tunneling in terms of through-bond and through-space interactions

A flexible grid framework forautomatic protein-ligand docking

Many important and fundamental questions in biology and biochemistry can be better understood through investigations performed at the protein-ligand or drug-receptor level. A variety of techniques have been used over the years, and it is an area of active research. In this paper we illustrate an approach that leverages a number of different computational chemistry approaches, and combines these with non-linear optimization algorithms and grid based high performance computing platforms. The result is a very flexible, high performance method of evaluating protein-ligand interaction algorithms. We illustrate the approach by evaluating a hybrid molecular modeling and quantum theoretical based algorithm

Radical Nature of C‑Lignin

The recently discovered lignin composed of caffeoyl alcohol monolignols or C-lignin is particularly intriguing given its homogeneous, linear polymeric structure and exclusive benzodioxane linkage between monomers. By virtue of this simplified chemistry, the potential emerges for improved valorization strategies with C-lignin relative to other natural heterogeneous lignins. To better understand caffeoyl alcohol polymers, we characterize the thermodynamics of the radical recombination dimerization reactions forming the benzodioxane linkage and the bond dissociation into radical monolignol products. These properties are also predicted for the cross-coupling of caffeoyl alcohol with the natural monolignols, coniferyl alcohol, sinapyl alcohol, and <i>p</i>-coumaryl alcohol, in anticipation of polymers potentially enabled by genetic modification. The average BDEs for the C-lignin benzodioxane α- and β-bonds are 56.5 and 63.4 kcal/mol, respectively, with similar enthalpies for heterodimers. The BDE of the α-bond within the benzodioxane linkage is consistently greater than that of the β-bond in all dimers of each stereochemical arrangement, explained by the ability the α-carbon radical generated to delocalize onto the adjacent phenyl ring. Relative thermodynamics of the heterodimers demonstrates that the substituents on the phenyl ring directly neighboring the bond coupling the monolignols more strongly impact the dimer bond strengths and product stability, compared to the substituents present on the terminal phenyl ring. Enthalpy comparisons furthermore demonstrate that the <i>erythro</i> stereochemical configurations of the benzodioxane bond are slightly less thermodynamically stable than the <i>threo</i> configurations. The overall differences in strength of bonds and reaction enthalpies between stereoisomers are generally found to be insignificant, supporting that postcoupling rearomatization is under kinetic control. Projecting the lowest-energy stereoisomer internal coordinates to longer polymer C-lignin strands highlights how significantly the stereochemical outcomes in polymerization may impact the macromolecular structure and in turn material and chemical properties. Through these comparisons of geometry, bond strengths, and reaction enthalpies, we shed light on the distinctive properties of C-lignin’s radical recombination and decomposition chemistry, and its potential as a natural lignin solution for biorefinery feedstocks and unique materials science applications

A Flexible Grid Framework forAutomatic Protein-Ligand Docking

Many important and fundamental questions in biology and biochemistry can be better understood through investigations performed at the protein-ligand or drugreceptor level. A variety of techniques have been used over the years, and it is an area of active research. In this paper we illustrate an approach that leverages a number of different computational chemistry approaches, and combines these with non-linear optimization algorithms and grid based high performance computing platforms. The result is a very flexible, high performance method of evaluating protein-ligand interaction algorithms. We illustrate the approach by evaluating a hybrid molecular modeling and quantum theoretical based algorithm. 1

Synthesis of Bioconjugated <i>sym</i>-Pentasubstituted Corannulenes: Experimental and Theoretical Investigations of Supramolecular Architectures

Applications of supramolecular architectures span a broad range of fields from medicinal chemistry to materials science and gas storage, making the design and synthesis of such structures a goal of high interest. The unique structural and symmetric properties of corannulene and the recent synthetic developments of <i>C</i>₅-symmetric pentafunctionalized derivatives motivate efforts to synthesize bioconjugated-corannulene systems and investigate their supramolecular assembly properties. Herein is presented the synthesis of <i>sym</i>-pentasubstituted corannulenes functionalized with sugar (galactose and ribose), oligopeptide, nucleosides (thymidine and deoxyadenosine), and palindromic oligonucleotide strands. Experimental and theoretical results demonstrate capability of supramolecular assembly formation in these constructs. Ab initio theoretical modeling enables further evaluation of structure and energetics of oligonucleotide-functionalized corannulene formation. Results indicate formation of aggregates, although icosahedral supramolecular formation is not observed. Analyses suggest future improvements to synthetic routes to achieve icosahedral architectures

Density Functional Theory Study of Spirodienone Stereoisomers in Lignin

The spirodienone structure in lignin is a relatively recent discovery, and it has been found to occur in lignin of various plant species at concentrations of ∼3%, which is sufficiently high to be important for better understanding of its properties and reactivity. The cyclic structure, with a β-1 bond, has been proposed to be a precursor for acyclic β-1 linkages in lignin. Previous analytical work has revealed the presence, but not the absolute configuration, of two stereoisomeric forms of spirodienone. The objective of the current work was to determine if there are thermodynamic differences that could help identify the experimentally observed stereoisomers. Results from density functional theory calculations reveal the presence of clusters of stereoisomers with varying stability that may be of use in narrowing the list of possible structures. Furthermore, the bond dissociation enthalpy of the cyclic ring exhibited a particularly high value for the C–O cleavage reaction relative to more conventional ether bonds in lignin, perhaps due to limited electron delocalization possibilities

Electronic Coupling Calculations for Bridge-Mediated Charge Transfer Using Constrained Density Functional Theory (CDFT) and Effective Hamiltonian Approaches at the Density Functional Theory (DFT) and Fragment-Orbital Density Functional Tight Binding (FODFTB) Level

In this article, four methods to calculate charge transfer integrals in the context of bridge-mediated electron transfer are tested. These methods are based on density functional theory (DFT). We consider two perturbative Green’s function effective Hamiltonian methods (first, at the DFT level of theory, using localized molecular orbitals; second, applying a tight-binding DFT approach, using fragment orbitals) and two constrained DFT implementations with either plane-wave or local basis sets. To assess the performance of the methods for through-bond (TB)-dominated or through-space (TS)-dominated transfer, different sets of molecules are considered. For through-bond electron transfer (ET), several molecules that were originally synthesized by Paddon-Row and co-workers for the deduction of electronic coupling values from photoemission and electron transmission spectroscopies, are analyzed. The tested methodologies prove to be successful in reproducing experimental data, the exponential distance decay constant and the superbridge effects arising from interference among ET pathways. For through-space ET, dedicated π-stacked systems with heterocyclopentadiene molecules were created and analyzed on the basis of electronic coupling dependence on donor–acceptor distance, structure of the bridge, and ET barrier height. The inexpensive fragment-orbital density functional tight binding (FODFTB) method gives similar results to constrained density functional theory (CDFT) and both reproduce the expected exponential decay of the coupling with donor–acceptor distances and the number of bridging units. These four approaches appear to give reliable results for both TB and TS ET and present a good alternative to expensive <i>ab initio</i> methodologies for large systems involving long-range charge transfers