Molecular Simulation

Molecular Simulations Inc. (MSI) software packages (InsightII 2000, Cerius² 4.2, and Quanta98), as well as Schrödinger Inc. software package, Macromodel. In the near future we will add a Materials Studio software package developed by MSI for the PC. These programs are widely used by chemists and non-chemists in research and teaching. All packages are designed to have a modular structure and we continuously try to increase not only the number of modules but their diversity as well.

Quantum Chemical Calculations– These computations are performed at different levels of accuracy. The most accurate level (and, consequently, the most computationally demanding) are the ab initio and density functional calculations. For high level calculations, we currently use Gaussian 98 (G98), DMOL³, Amsterdam Density Functional (ADF), Plane Wave, QuanteMM, Turbomole, NWChem, and Molpro packages. The first seven programs are accessible through graphical interfaces (Cerius², InsightII, GaussView and NWChem JAVA interface) and used not only in research but also in education. Next in accuracy are semi-empirical calculations, represented in the LMS by Mopac and Zindo. Since these programs are accessible from the Cerius² interface, they are also used in education. The least accurate level, but most time efficient, are molecular mechanics calculations. Force field optimizations are routinely applied in obtaining initial geometries for higher level calculations, in conformer searches, and in quick assessments of steric influences.

The molecular modeling series starts with an introductory lecture (separately taught for chemists and non-chemists) and continues with a tutorial session. During the tutorial, students learn how to perform simple visualization, building and minimization operations within the Insight or Cerius² platforms. This course was taught once during this fiscal year with 22 chemistry and 8 non-chemistry students and faculty participating.

The highest level of training we currently offer is the ab initio short course. Classes meet every day for about three weeks. Theoretical lectures on quantum chemistry are followed by computer exercises oriented toward the use of Gaussian 98 through the Cerius² interface. Homework is assigned every day and the short course is finished with an individual research project for each student and a small presentation to the group. This year 8 students participated in this workshop.

 Molecular simulations are useful for assessing both the flexibility of the dendrimer backbone and the possible proximities of appended moieties. Accordingly, molecular models were grown in a divergent manner for generation 2-5 amine-terminated PPI dendrimers.  Molecular models were created using the Cerius2 (version 4.0) software package (Molecular Simulations, Inc.; San Diego, CA). The DREIDING forcefield version 2.21 was used for optimization and molecular dynamics simulations. Specifically, each generation of PPI dendrimers was constructed from a model of the previous generation by adding the appropriate number of propyl amine branches. Molecular dynamics (MD) simulations were then performed by the NVT method (constant volume and temperature) using the Nosé temperature thermostat (0.01 ps relaxation) for 10 ps at 1000 K, followed by 250 ps at 300 K with a step size of 1 fs. The structures were again energy minimized. After obtaining models of each generation, all primary amines were functionalized with pyrene butyric acid, thereby mimicking the synthetic procedure used to prepare the authentic materials. Minimization and dynamics were performed again, exactly as described for the unmodified dendrimers.

The results of the molecular dynamic analysis (Figure V-1) show that in the case of PPI-Py8 and PPI-Py16, the pyrene moieties are able to wrap completely around the dendrimer, resulting in a single, aggregated clump of pyrene molecules. However, due to the size of PPI-Py32 and PPI-Py64 and the resulting steric congestion on the surface of these materials, the lowest-energy structures are those forming smaller pyrene aggregates. Fluorescence emission spectra on all four generations of pyrene-modified dendrimers in dimethyl formamide (DMF) solvent exhibited a broad excimer emission centered at 476 nm. The excimer fluorescence arises from the close proximity of pyrene functional groups on individual dendrimers. These results are supported by the molecular modeling studies. Experimental work also shows that the excimer-to-monomer ratio increases with increasing generation; a result that can be explained by the increase in the density of pyrene groups on the dendrimer periphery with increasing generation, in agreement with the molecular dynamic models.

2.Insight into the Separation Mechanism of Chiral Neutral Analytes by Charged Cyclodextrins Using Capillary Electrophoresis with D. Maynard and G. Vigh, Department of Chemistry.Cyclodextrins (CDs) are some of the most widely used chiral resolving agents in capillary electrophoresis (CE) for the separation of pharmaceutical compounds. ", $, and ( cyclodextrins are neutral, cyclic oligosaccharides composed of 6,7, and 8 D(+)- glucopyranose units, respectively, and are connected through (1,4) linkages. Cyclodextrins are thought to form inclusion complexes with analytes, where the inclusion depends upon the inner diameter of the cavity and size of the analyte. The dynamic equilibrium between the host and guest molecules produces diastereomers with different effective mobilities, which can be separated using CE.

Due to its low solubility in water, $-cyclodextrin has been derivatized with neutral hydrophyllic functional groups to increase its aqueous solubility. However, these neutral cyclodextrins can only be used to separate charged analytes in CE. In order to separate neutral analytes, CDs have been derivatized with charged functional groups. However, most commercially available charged cyclodextrins are complex mixtures of many isomers, i.e., the position and number of charged functional groups vary from molecule to molecule. This leads to different binding constants and different enantio-selectivities. Furthermore, molecular level spectroscopic information cannot be obtained. As a result, rational experimental design cannot be accomplished. Recently, a 14-charged CD was synthesized, and characterized through x-ray crystallography, that would probe the unique separation selectivity associated with charged functional groups on both the primary and the chiral, or secondary, face of the CD.

The solvent accessible Connelly surface for a precursor to the 14-charged CD, heptakis(2-O-methyl)-$-CD with a space filling model of an included ethanol molecule (A, Figure V-2) that was present in the crystal was created using the software package InsightII. The Connelly surface provided useful insight into the CD cavity volume, which can be used as a reference point for other CD derivatives. In addition, the solvent accessible Connolly surfaces were used to compare the CD cavity size available for analyte inclusion complexation between the newly synthesized 14-charged CD, heptakis(2-O-methyl-3,6-di-O-sulfato)-$-CD (B, Figure V-2) and another structurally similar, single-isomer CD, heptakis(2-O-methyl-6-O-sulfato)-$-CD (C, Figure V-2). The observed CE separation selectivity differences for the same analytes using these two cyclodextrins can be rationalized by examining the Connelly surfaces. As a result, it became clear that an entirely different separation mechanism is at work: the large, hydrophobic cavity of C can accommodate a hydrophobic planar molecule much more easily than B, whose cavity access is restricted.

3.Intercalation of a B Molecular Acid Complex of Mercury into B-Base Trinuclear Gold Complexes to Form Supramolecular Chain Assemblies with J. P. Fackler, Jr., T. A. Grant, M. A. Omary, M. A. Rawashdeh-Omary, Department of Chemistry; B. R. Pietroni, Harvard University; R. J. Staples, A. Burini, R. Galassi, Camerino University, Italy.The trinuclear cyclic Au^I compound [Au(F-C²,N³-bzim)]₃ (bzim=1-benzylimidazolate), 1 (Figure V-3), has been shown to interact with metal cations such as Ag^I and Tl^I to form "sandwich" complexes in which six Au^I atoms from two trinuclear gold molecules bond to the Ag^I or Tl^I. Furthermore, the sandwich units stack to form linear chains with an intermolecular aurophilic Au^I-Au^I bonding between four of the six Au^I atoms in adjacent units.

The trinuclear Au^I compounds interact with cations in a manner similar to the cation B-acid complexes studied by Dougherty. Since Hawthorne and others have demonstrated that polynuclear mercury complexes form crown compounds with anions and various organic and aromatic organometallic substrates, it, therefore, becomes plausible that acid-base stacking might occur between the trinuclear Hg^II complex [Hg ((F-C,C-C₆F₄)]₃, 2 (Figure V-3), and the trinuclear Au^I complexes. Herein we describe the interactions between the base 1, and the acid 2, using DFT single point energy calculations at the x-ray crystal structure geometries, with the functional B3LYP and a double-. quality basis set.

4.An Intramolecular Boron-Boron One-Electron F-Bond with J. D. Hoefelmeyer and F. Gabbaï, Department of Chemistry. Owing to their isoelectronic relationship to neutral methyl radicals, the chemistry of stable boron-centered radical anions R₃B^!- (R=aryl rings) has been investigated intensely. Although delocalization of the radical over the aryl rings accounts for the stability of such systems, EPR studies show that, in some instances, the unpaired electron is mainly localized at boron. In organodiboranes, one-electron reduction leads to the formation of a one-electron F-bond formed by the overlap of the parallel p_z boron orbitals. Interestingly, the isolation of boron radicals in which the unpaired electron occupies a molecular orbital formed by the combination of overlapping colinear atomic orbitals is much more elusive. Motivated by the importance of stable radicals to the field of material science, we have set out to prepare a stable boron radical, of the general form (R₃B)₂^!-, and report on the formation of a radical that features a boron-boron one electron F-bond.

A single-crystal X-ray analysis of 1,8-bis(diphenylboryl)-naphthalene (Figure V-5, 1) revealed the existence of a sterically congested structure with a boron-boron distance of 3.002(2) Å. A one-electron reduction of 1 affords the radical anion 2, shown in Figure V-5. While it has so far not been possible to obtain single crystals of 2, we have performed a series of DFT calculations on both 1 and 2 using the function B3LYP as implemented in Gaussian 94, and the 6-31G basis set on C, and H, and the 6-31+G* basis set on B. The calculated structure of 1 is in good agreement with that determined experimentally by diffraction methods.

While all bond distances and angles are in good agreement, we note that the calculated boron-boron intramolecular distance (3.16 Å) is slightly overestimated by the calculation. Nevertheless, examination of the DFT orbitals reveals that, in 1, the p_z orbitals of the neighboring boron centers overlap substantially and contribute to the Lowest Unoccupied Molecular Orbital (LUMO), shown in Figure V-6. The calculated structure from 2 differs from that of 1 in several aspects, but most noteworthy is that the boron-boron distance decreases substantially (3.16 Å in 1 to 2.82 Å in 2) in agreement with the presence of a bonding interaction. As shown in Figure V-6, both boron atoms are the dominant contributors to the singly occupied Highest Occupied Molecular Orbital (HOMO), which has a strong boron-boron F-bond character. This one-electron F-bond can be viewed as the occupation of the formerly vacant boron p_z-orbitals upon one-electron reduction of 1. The minor contributions of the ring carbon atoms substantiate the importance of the stabilizing effect provided by aryl substituents in stable radicals.

5.A Theoretical Study of the Primary Oxo Transfer Reaction of a Dioxo Molybdenum(VI) Compound with Imine Thiolate Chelating Ligands: A Molybdenum Oxotransferase Analogue with L. M. Thomson and M. B. Hall, Department of Chemistry.  Molybdenum containing enzymes are a broad class of enzymes that are essential for the metabolism of carbon, nitrogen and sulfur in a wide variety of organisms. In humans, sulfite oxidase is the enzyme responsible for the metabolism of the toxin sulfite to sulfate. Analogue reaction systems have been developed to mimic the activity of the molybdoenzymes. These analogue systems can be used to verify experimental data on the structure and reaction mechanism of the complex enzyme systems. This study focuses on the elucidation of the reaction mechanism of an analogue system.

Density functional calculations on MoO₂(NHCHCH₂SH)₂ + P(CH₃)₃ ÿ MoO(NHCHCH₂SH)₂ + OP(CH₃)₃ were performed at the B3P86 level of theory as implemented in Gaussian 94, using a double-. quality basis set for all atoms and the inclusion of a polarization function on the phosphorus. The DFT results indicate that this reaction proceeds through a two step mechanism via an associative intermediate shown in Figure V-7.

The substrate was found to attack one of the terminal oxo groups to form an unusual 3c-4e^- O-P-C bond in the first transition state, TSI. The OP(CH₃)₃ group then rotates to almost lie in the MoO₂ plane to form the intermediate, INT. The second transition state, TSII, involves the weakening of the Mo-OP(CH₃)₃ bond and the concomitant rearrangement of the ligands. Figure V-8 shows an important anti-bonding interaction that helps to eliminate the product, OP(CH₃)₃. The overall exothermicity of this reaction is 32.7 kcal/mol (-)H^o) and )G^o = -27.1 kcal/mol, a value consistent with the equilibrium lying far to the right. The )H^‡ for the first step (rate determining) was found to be 9.4 kcal/mol, and the second step had a )H^‡ = 3.3 kcal/mol. These results are within the uncertainty of the experimental system, for which the rate determining )H^‡ = 9.6(6).

We provide help to the entire A&M campus in Gaussian, InsightII, Cerius², and Macromodel related questions. Also, we benchmark the quantum chemistry packages for the supercomputer center and assist with testing and installation. We relay user questions to the software companies and keep the manuals and other documentation available for checkout or immediate use. A web page has also been set up at http://www.chem.tamu.edu/LMS to assist users of the LMS by supplying a list of software and hardware available through the LMS, on-line manuals for most of the programs available, information on upcoming workshops and much more.

"A Theoretical Study of the Primary Oxo Transfer Reaction of a Dioxo Molybdenum(VI) Compound with Imine Thiolate Chelator Ligands: A Molybdenum Oxotransferase Analogue," L. M. Thomson, and M. B. Hall, submitted to J. Am. Chem. Soc. (2000).

"Primary and Secondary Processes in the Photodissociation of CHBr₃," W. S. McGivern, O. Sorkhabi, A. G. Suits, and A. Derecskei-Kovacs, J. Phys. Chem. A, 000 (2000).

"Supramolecular Chain Assemblies Formed by Interaction of a B Molecular Acid Complex of mercury with B-Base Trinuclear Gold Complexes," A. Burini, J. P. Fackler, Jr., R. Galassi, T. A. Grant, M. A. Omary, M. A. Rawashdeh-Omary, B. R. Pietroni, and R. J. Staples, J. Am. Chem. Soc.,000 (2000).

"An Intramolecular Boron-Boron One-Electron F-Bond," J. Hoefelmeyer and F. Gabbaï, J. Am. Chem. Soc., 122, 9054 (2000).

Web Site: http://www.chem.tamu.edu/LMS

Lisa M. Thomson

Phone:     (979) 845-9384

Fax:         (979) 845-2971

E-mail:     mouse@mail.chem.tamu.edu

Office:     Room 2109, Chemistry Building