Biomedical subjects

Lawrence M Pratt

Publications and source records attributed to Lawrence M Pratt.

16 recordsLinked to original sources

PubMed2006

Novel diborane-analogue transition structures for borane reactions with alkyl halides.

Ab initio and DFT calculations were performed to examine the mechanisms of reduction of alkyl halides and formaldehyde by borane. With alkyl halides, the optimized transition structure geometry resembled diborane, with a pair of hydrogen atoms bridging the boron and carbon atoms by three-center-two-electron bonds. A similar transition structure was found for the reduction of formaldehyde, although it was not the lowest-energy transition structure. Solvation by dimethyl ether or dimethyl sulfide disrupted this bridging with chloromethane, while both ligands dissociated from borane during the reduction of formaldehyde. The high calculated activation free energies of alkyl halide reduction are consistent with their observed lack of reactivity with borane.

Journal Article↗

PubMed2005

Gas-phase reactions of lithium dimethylaminoborohydride and related species.

[reaction: see text] Ab initio and density functional theory (DFT) calculations were used to examine the mechanisms of reduction and amination of chloromethane by lithium dimethylaminoborohydride (LAB) in the gas phase. For comparison, the amination of chloromethane by lithium dimethylamide and the reduction by borane, diborane, and borohydride ions were also examined. The reduction of chloromethane by LAB occurred most readily from a conformation that allowed coordination of the lithium atom to the chloride leaving group, and the most favorable amination pathway occurred by a backside attack of the nitrogen nucleophile on chloromethane.

Journal Article↗

PubMed2005

A computational study of mixed aggregates of chloromethyllithium with lithium dialkylamides.

DFT calculations were performed to examine the possible formation of mixed aggregates between chloromethyllithium carbenoids and lithium dimethylamide (LiDMA). In the gas phase mixed aggregates were readily formed and consisted of mixed dimers, mixed trimers, and mixed tetramers. THF solvation disfavored the formation of mixed tetramers and resulted in less exergonic free energies of mixed dimer and mixed trimer formation.

Journal Article↗

PubMed2005

A computational study of oxiranyllithium.

[reaction: see text] Computational methods were used to determine the structure, bonding, and aggregation states of oxiranyllithium in the gas phase and in THF solution, at 200 and 298 K. THF solvation was modeled by microsolvation with explicit THF ligands, forming a supermolecule that includes the oxiranyllithium aggregate and its first solvation shell. Because oxiranyllithium has a chiral center, two diastereomeric dimers were formed, the RR and the RS, along with their enantiomers. Similarly, three diastereomers of the tetramer were formed, the RRRR, RRRS, and RRSS and their enantiomers. Oxiranyllithium was found to exist predominantly as the tetramer in the gas phase, while the dimer was the dominant species in THF solution. The relative concentrations of the different stereoisomers were calculated from equilibrium constants.

Journal Article↗

PubMed2005

Computational strategies for evaluating barrier heights for gas-phase reactions of lithium enolates.

Gas-phase activation energies were calculated for three lithium enolate reactions by using several different ab initio and density functional theory (DFT) methods to determine which levels of theory generate acceptable results. The reactions included an aldol-type addition of an enolate to an aldehyde, a proton transfer from an alcohol to a lithium enolate, and an S(N)2 reaction of an enolate with chloromethane. For each reaction, the calculations were performed for both the monomeric and dimeric forms of the lithium enolate. It was found that transition state geometry optimization with B3LYP followed by single point MP2 calculations generally provided acceptable results compared to higher level ab initio methods.

Journal Article↗

PubMed2005

Structure, bonding, and solvation of lithium vinylcarbenoids.

[reaction: see text] Molecular modeling was used to determine the structure of lithium vinylcarbenoids in the gas phase and in THF solution. Solvent effects were modeled by microsolvation with explicit THF ligands on each of the lithium atoms. The carbenoid geometries are dependent on the heteroatom and on solvation. The calculations predict 1-chlorovinyllithium and 1-bromovinyllithium to be a mixture of monomer and dimer at 200 K and mostly monomer at higher temperatures, whereas the 1-fluoro-, 1-methoxy-, and 1-dimethylaminovinyllithium are predicted to be dimeric in solution.

Lithium↗

PubMed2005

N,O-dilithio-2-(N-methylamino)ethanol: an intramolecular mixed aggregate.

Density functional theory and infrared spectroscopy were used to determine the structure of N,O-dilithio-2-(N-methylamino)ethanol, a mixed intramolecular aggregate. The calculations indicated that the cyclic form of this compound is more stable than the open form, and that conclusion is consistent with the infrared spectra. The solid-state spectra showed lower Li-N and Li-O vibrational frequencies than were calculated for the gas phase, which is consistent with coordination of lithium to electronegative atoms on adjacent molecules in the solid state.

Journal Article↗

PubMed2004

Electronic structure of persistent radicals: nitroxides.

The molecular and electronic structures of 10 free nitroxide radicals have been investigated by HeI/HeII photoelectron spectroscopy (UPS), DFT calculations, and comparison with the spectra of related compounds. We observe that the electronic structure of the nitroxide group is unaffected by substitution except in a carbonyl derivative where nitroxide group orbitals are noticeably stabilized. Also, we have detected small variations in the photoionization cross-sections for singlet and triplet states of cation, the states belonging to the same electron configuration. The relationship between electronic structure and radical reactivity is discussed, and an experimentally based estimate of delocalization energy of the unpaired electron is given. Some conflicting kinetic data on radical reactivity have been analyzed in view of the UPS results.

Journal Article↗

PubMed2004

Structure, bonding, and solvation of dilithiodiamines.

Computational methods were used to determine the structure of dilithiodiamines and the effects of solvation by ethereal solvents. Solvation was examined by the use of microsolvation with explicit dimethyl ether or THF ligands and by the combined use of microsolvation and the IEFPCM continuum solvent model. It was determined that each of the compounds studied exists exclusively as a bridged intramolecular dimer, both in the gas phase and in solution. Thermodynamic properties were calculated at 200 and 298 K to estimate the effect of temperature on the cyclization energies. Infrared spectroscopy was used to confirm the proposed intramolecular dimer structures.

Crystallography, X-Ray↗

PubMed2004

Leaving group effects in gas-phase substitutions and eliminations.

Using a methodology recently developed for studying the product distributions of gas-phase S(N)2 and E2 reactions, the effect of the leaving group on the reaction rate and branching ratio was investigated. Using a dianion as the nucleophile, reactions with a series of alkyl bromides, iodides, and trifluoroacetates were examined. The alkyl groups in the study are ethyl, n-propyl, n-butyl, isobutyl, isopropyl, sec-butyl, and tert-butyl. The data indicate that leaving group abilities are directly related to the exothermicities of the reaction processes in both the gas phase and the condensed phase. Gas-phase data give a reactivity order of iodide > trifluoroacetate > bromide for S(N)2 and E2 reactions. Previous condensed phase data indicate a reactivity order of iodide > bromide > trifluoroacetate for substitution reactions; however, the basicities of bromide and trifluoroacetate are reversed in the condensed phase so this reactivity pattern does reflect the relative reaction exothermicities. Aside from this variation, the gas-phase data parallel condensed phase data indicating that the substituent effects are rooted in the nature of the alkyl substrate rather than in differences in solvation. The experimental data are supported by calculations at the MP2/6-311+G(d,p)//MP2/6-31+(d) level.

Journal Article↗

PubMed2004

Lithiated hydrocarbons, their conjugate bases, and corresponding radicals: a computational study of RLi (R = CH3, CH3CH2, CH2=CH, and HC triple bond C).

Organolithium compounds RLi (R = CH(3), CH(3)CH(2), CH(2)=CH, and HC(triple bond)C) and their corresponding hydrocarbons were fully optimized at the MP2/6-311+G(2df,2pd) level. Single-point energy calculations also were carried out at the CCSD(T) and B3LYP levels with the same triple split-valence basis set. Acidities, electron affinities, and bond dissociation energies are reported, and the following general results were found: (1) Alpha-lithio anions are ground-state triplet molecules. (2) Lithium is an acid-enhancing substituent. (3) Conjugate bases of organolithiums are stable with respect to electron loss and therefore are attractive targets for mass spectrometry investigations. (4) Lithium weakens alpha- and beta-C-H bonds, the latter by approximately 25 kcal mol(-1). Consequently, radical chemistry of lithiated compounds at remote sites is a promising area for exploration.

Journal Article↗

PubMed2004

Tetrafluorobenzyne thermochemistry: experiment and theory.

Gas-phase thermodynamic properties of 1,2,3,4-tetrafluorobenzyne (1 H-(2)) were determined by Fourier transform mass spectrometry and ab initio and density functional theory methods. 1,2,3,4-Tetrafluorobenzyne radical anion was generated by abstraction of a proton and a hydrogen atom upon reaction of 1,2,3,4-tetrafluorobenzene (1) with O(-.). The resulting structure was confirmed by converting it to a species which could be independently prepared. Bracketing results provided the proton affinity of 1,2,3,4-tetrafluorobenzyne radical anion and the electron affinities of 1,2,3,4-tetrafluorobenzyne and 1,2,3,4-tetrafluorophenyl radical. These measured values were combined in a thermodynamic cycle to provide the heat of hydrogenation of 1 H(2) (DeltaH degree (hyd) = 367 +/- 18 kJ mol(-1)) and the first and second CH bond dissociation energies of 1 (481 +/- 11 and 321 +/- 13 kJ mol(-1)). The same approach failed for the meta and para isomers, but their energetics were examined using B3LYP and CCSD(T) computations.

Drug Design↗

PubMed2003

Solvent effects on the aggregation state of lithium dialkylaminoborohydrides.

DFT calculations were performed to determine the effects of ethereal solvents on the aggregation state of lithium dialkylaminoborohydrides (LABs). The calculations included dimerization energies in the gas phase, with continuum solvation only, microsolvation with coordinating ethereal ligands, and a combination of the microsolvation and continuum models. The continuum model alone overestimates the stability of the dimers, apparently due to the lack of steric effects from the coordinating ethereal ligands. The use of the combined microsolvation and continuum solvation models predicts lithium dimethylaminoborohydride to be a mixture of monomer and dimer in THF, and more sterically hindered lithium aminoborohydrides to exist primarily as monomers. The kinetics of amination of 1-chlorodecane by lithium dimethylaminoborohydride showed no detectable change in reaction rate with time, suggesting that the LAB reagent may exist primarily as a monomer in THF.

Journal Article↗

PubMed2003

Ketone enolization with lithium dialkylamides: the effects of structure, solvation, and mixed aggregates with excess butyllithium.

The effects of lithium dialkylamide structure, mixed aggregate formation, and solvation on the stereoselectivity of ketone enolization were examined. Of the lithium dialkylamides examined, lithium tetramethylpiperidide (LiTMP) in THF resulted in the best enolization selectivity. The stereoselectivity was further improved in the presence of a LiTMP-butyllithium mixed aggregate. The use of less polar solvents reduced the enolization stereoselectivity. Ab initio calculations predict LDA and LiTMP to form mixed cyclic dimers in ethereal solvents. The calculations also predict LiTMP-alkyllithium mixed aggregates to competitively inhibit the formation of less stereoselective LiTMP-lithium enolate mixed aggregates.

Chemical Phenomena↗

PubMed2003

A computational study of lithium enolate mixed aggregates.

Ab initio calculations were performed to examine the formation of mixed dimer and trimer aggregates between the lithium enolate of acetaldehyde (lithium vinyloxide, LiOV) and lithium chloride, lithium bromide, and lithium amides. Gas-phase calculations showed that in the absence of solvation effects, the mixed trimer 2LiOV.LiX is the most favored species. Solvation in ethereal solvents was modeled by a combination of specific coordination of dimethyl ether ligands on each lithium and "dielectric solvation" (DSE, dielectric solvation energies), immersion of each molecule in a cavity within a continuous dielectric having the dielectric constant of THF at room temperature. DSE is less important for aggregates (reduced dipoles or quadrupoles) than monomers (dipoles) and is also reduced for the coordinatively solvated species. Both solvation terms reduce the exothermicity of aggregation. In many cases, lithium salts that are three- rather than four-coordinate have significant populations at room temperature. The strongly basic lithium amides prefer mixed aggregates with weaker bases than homoaggregates. The computational results are consistent with the limited experimental data available.

Journal Article↗

PubMed2002

Structures and aggregation states of fluoromethyllithium and chloromethyllithium carbenoids in the gas phase and in ethereal solvent.

Using high-level quantum mechanical calculations and various models to account for solvation effects, monomers and dimers of fluoromethyllithium and chloromethyllithium carbenoids are studied in the gas phase and in dimethyl ether solvent. A combination of explicit microsolvation and a continuum reaction field is required to account fully for the structural and energetic effects of solvation. One important effect of solvent is the stabilization of charge-separated structures in which the lithium-halogen distance is much greater than in the gas-phase structures. At the most complete level of theory the 173 K standard-state free energy of dimerization of fluoromethyllithium in dimethyl ether is predicted to be -0.9 kcal mol(-)(1), while that for chloromethyllithium in the same solvent is predicted to be 3.7 kcal mol(-)(1). This suggests that, under typical experimental conditions, dimers of chloroalkyllithiums will not be observed, while dimers of fluoroalkyllithiums may contribute to the equilibrium population at a detectable level.

Journal Article↗