Biomedical subjects

Weston Thatcher Borden

Publications and source records attributed to Weston Thatcher Borden.

At least 19 recordsLinked to original sources

PubMed2007

Tunneling in the 1,5-hydrogen shift reactions of 1,3-cyclopentadiene and 5-methyl-1,3-cyclopentadiene.

MPW1K/6-31+G(d,p) calculations which include the effects of small curvature tunneling find that, around room temperature, thermally activated tunneling dominates the 1,5-hydrogen shift reactions of 1,3-cyclopentadiene (2a) and 5-methyl-1,3-cyclopentadiene (2c). The calculated temperature dependence of the H/D kinetic isotope effect (KIE) for the latter rearrangement agrees well with experimental measurements that were published nearly 40 years ago. It is argued that the experimental KIEs provide prima facie evidence for tunneling in this reaction. The calculations also predict that it should be possible, at least in principle, to confirm this conclusion by observing curvature in the Arrhenius plot for the rearrangement of 2c.

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PubMed2006

Ab initio calculations of the potential surface for rearrangement of 2,2,3,3-tetrafluoromethylenecyclopropane to 1-(difluoromethylene)-2,2-difluorocyclopropane.

(4/4)CASSCF and CASPT2 calculations have been performed to understand the reason that addition of a second pair of geminal fluorines to methylenecyclopropane lowers the barrier to rearrangement by 6.7 kcal/mol more than addition of the first pair. Our calculations duplicate this experimental finding by Dolbier and co-workers. Our computational results confirm Dolbier's conjecture, that the non-additive lowering of Ea for the rearrangement of 2,2,3,3-tetrafluoromethylenecyclopropane (9) to 1-(difluoromethylene)-2,2-difluorocyclopropane (11) is due to destabilization of 9 by the presence of the vicinal CF2 groups in this fluorocarbon. In the course of exploring the potential energy surface for the rearrangement of 9, we have located a bond-stretch isomer (20) that differs from 9 by inversion of both CF2 groups. The enthalpy of 20 is computed to be 21.9 kcal/mol higher than that of 9, but direct interconversion of these two "bond-stretch invertomers" requires passage over a TS whose enthalpy is calculated to be 11.7 kcal/mol higher than that of 20.

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PubMed2006

Why does perfluorination render bicyclo[2.2.0]hex-1(4)-ene stable toward dimerization? Calculations provide the answers.

B3LYP calculations with two different basis sets have been performed to understand why bicyclo[2.2.0]hex-1(4)-ene (1a) undergoes dimerization with DeltaH(++) = 11.5 kcal/mol, but dimerization of perfluorobicyclo[2.2.0]hex-1(4)-ene (1b) has never been observed. The former reaction is computed to be exothermic by 37.2 kcal/mol, whereas the latter is calculated to be endothermic by 7.4 kcal/mol. The 44.6 kcal/mol difference between the enthalpies of these two reactions can be dissected into contributions of 24.5 kcal/mol for the difference between the enthalpies for forming diradical intermediates 2a and 2b and 20.1 kcal/mol for cyclization of 2a and 2b to, respectively, 3a and 3b. The latter enthalpy difference is largely attributable to repulsions between the endo-fluorines in the dimer, although the exo-fluorines also are found to contribute. The former enthalpy difference is attributable to the difference between the dissociation enthalpies of the pi bonds in 1a and 1b, which is shown to amount to 16 +/- 1 kcal/mol. About 25% of the stronger pi bond in fluoroalkene 1b is found to be due to hyperconjugation of the eight C-F bonds in 1b with the filled pi orbital. However, the major contributor to the stronger pi bond in 1b is shown to be the unfavorable interaction that results when a pyramidalized radical center is syn to a C-F bond. Both of these effects, which contribute to the greater strength of the pi bond in 1b, relative to that in 1a, are analyzed and discussed.

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PubMed2006

Evidence for the formation of the (Ph3P)2Pt complex of 3,7-dimethyltricyclo[3.3.0.03,7]oct-1(5)-ene, the most highly pyramidalized alkene in a homologous series. Isolation and X-ray structure of the product of the ethanol addition to the complex.

[reaction: see text] Attempts to isolate the (Ph(3)P)(2)Pt complex of the highly pyramidalized olefin 3,7-dimethyltricyclo[3.3.0.0(3,7)]oct-1(5)-ene 2 by generation of 2 in the presence of (Ph(3)P)(2)PtC(2)H(4), followed by crystallization of the complex (2-Pt) from THF-ethanol, resulted in the isolation of the adduct of 2-Pt with ethanol (5). Calculations confirm that addition of alcohol across the C1-C5 bond is more favorable in 2-Pt than in the corresponding (Ph(3)P)(2)Pt complexes of less pyramidalized olefins, despite the stronger Pt-C bonds in 2-Pt.

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PubMed2006

Cooperative and competitive effects of substituents at C1 and C4 on the barriers to ring inversion of 5,5-difluorobicyclo[2.1.0]pentanes.

To identify the reasons for the very low barrier that has been measured for ring inversion of 1,4,5,5-tetrafluorobicyclo[2.1.0]pentane (deltaG(double dagger) = 6.8 +/- 0.2 kcal/mol), CASSCF and CASPT2 calculations have been performed on ring inversion in this and other bicyclo[2.1.0]pentanes. The results of the calculations show that a cooperative interaction between the geminal fluorines at C2 and the fluorines at C1 and C3 in the singlet cyclopentane-1,3-diyl transition structure (TS) contributes 3.7 kcal/mol to lowering the barrier to ring inversion in the tetrafluoro compound. In contrast, a competitive substituent effect in the TS for ring inversion of 1,4-dicyano-5,5-difluorobicyclo[2.1.0]pentane is predicted to raise the barrier height by 6.1 kcal/mol. The origin of these cooperative and competitive substituent effects is discussed.

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PubMed2005

Heat of hydrogenation of 1,5-dehydroquadricyclane. A computational and experimental study of a highly pyramidalized alkene.

The radical anion of the highly pyramidalized alkene 1,5-dehydroquadricyclane (1) was generated in the gas phase from the Squires reaction of 1,5-bis(trimethylsilyl)quadricyclane with F-/F2. The electron binding energy and proton affinity of 1*- were determined by bracketing experiments to be 0.6 +/- 0.1 eV and 386 +/- 5 kcal/mol, respectively. These values are in good agreement with values predicted by density functional theory (B3LYP/6-31+G*) and ab initio (CASPT2/6-31+G*) calculations. The experimental heat of hydrogenation of 1, obtained from a thermochemical cycle, was found to be 91 +/- 9 kcal/mol. This value of deltaH(H2) leads to values of 67 +/- 9 kcal/mol for the olefin strain energy (OSE) of 1, 172 +/- 9 kcal/mol for its heat of formation, and 23 +/- 9 kcal/mol for its pi bond dissociation enthalpy. Since the retro-Diels-Alder reaction of neutral 1 is computed to be highly exothermic, the finding that 1*- apparently does not undergo a retro-Diels-Alder reaction is of particular interest. The B3LYP/6-31+G* optimized geometry of 1 suggests that the bonding in this alkene is partially delocalized, presumably because the highly pyramidalized double bond in 1 interacts with the distal cyclopropane bonds in a manner that eventually leads to a retro-Diels-Alder reaction. The good agreement of the B3LYP and (2/2)CASPT2 values for the heat of hydrogenation and OSE of 1 with the experimentally derived values provides indirect evidence for the correctness of the B3LYP prediction that the equilibrium geometry of 1 lies part way along the reaction coordinate to the transition structure for the retro-Diels-Alder reaction.

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PubMed2005

Computational studies of the thermal fragmentation of P-arylphosphiranes: have arylphosphinidenes been generated by this method?

CASSCF, CASPT2, CCSD(T), and (U)B3LYP electronic structure calculations have been performed in order to investigate the thermal fragmentation of P-phenylphosphirane (1) to phenylphosphinidene (PhP) and ethylene. The calculations show that generation of triplet PhP via a stepwise pathway is 21 kcal mol(-1) less endothermic and has a 12 kcal mol(-1) lower barrier height than concerted fragmentation of 1 to give singlet PhP. The formation of singlet PhP via a concerted pathway is predicted to be stereospecific, whereas formation of triplet PhP is predicted to occur with complete loss of stereochemistry. However, calculations on fragmentation of anti-cis-2,3-dimethyl-P-mesitylphosphirane (cis-1Me) to triplet mesitylphosphinidene (MesP) indicate that this reaction should be more stereospecific, in agreement with the experimental results of Li and Gaspar. Nevertheless, with a predicted free energy of activation of 42 kcal mol(-1), the formation of MesP from cis-1Me is not likely to have occurred in an uncatalyzed reaction at the temperatures at which this phosphirane has been pyrolyzed.

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PubMed2005

Experimental and theoretical study of stabilization of delocalized forms of semibullvalenes and barbaralanes by dipolar and polarizable solvents. Observation of a delocalized structure that is lower in free energy than the localized form.

[reaction: see text] UV/vis spectra of thermochromic semibullvalenes 1 and barbaralanes 2, which undergo rapid degenerate Cope rearrangements, display temperature-dependent shoulders (1b, 1d, 1e) or absorption maxima (1c, 2c, 2f) at the low-energy side of their strong UV bands. These long-wavelength absorptions are ascribed to Franck-Condon transitions from delocalized structures 1(deloc) and 2(deloc). Gibbs free energy differences, DeltaG*, between delocalized and localized forms were calculated from the temperature dependence of the long-wavelength absorptions. Dipolar and polarizable solvents strongly affect and even may reverse the relative stabilities of the localized and delocalized forms of 1c, 2c, and 2f. For example, DeltaG*(2c) = 8 kJ mol(-)(1) in cyclohexane, 2 kJ mol(-)(1) in dimethylformamide, and -3 kJ mol(-)(1) in N,N'-dimethylpropylene urea (DMPU), so that (2c(deloc))(DMPU) becomes the global minimum. In contrast to the case for 2c, the intensities of the long-wavelength shoulders of the yellow semibullvalenes 1b, 1d, and 1e are only moderately influenced by solvents, and the rates of Cope rearrangements of the nonthermochromic, colorless barbaralanes 2a and 2b, determined by NMR methods, are almost solvent-invariant. In search of the solute properties that are decisive in determining the influence of solvent upon DeltaG*, electrical dipole and quadrupole moments and molecular polarizabilities have been calculated using the B3LYP/6-31G* method and solvation energies have been computed with the conductorlike polarized continuum model (CPCM). The results of these calculations indicate that the solvent effects are due to the greater polarity and polarizability of the delocalized structures relative to the localized structures.

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PubMed2005

Factors controlling the barriers to degenerate hydrogen atom transfers.

High-level electronic structure calculations have been used to study the factors contributing to the barriers to degenerate hydrogen-atom transfer (HAT) reactions. Understanding of these reactions is a prerequisite to the development of any more general theory of HAT reactions, and yet, the existing models for such reactions perform quite poorly when applied to even simple self-exchanges. The reasons behind these failures are elucidated in the present work. They include a near cancellation of bond-strength effects between reactant and transition state, as well as a strong dependence of the geometry of the transition state on the nature of the heavy atoms.

Ammonia↗

PubMed2005

How important is bishomoaromatic stabilization in determining the relative barrier heights for the degenerate Cope rearrangements of semibullvalene, barbaralane, bullvalene, and dihydrobullvalene?

[structure: see text] B3LYP/6-31G* calculations have been used to investigate the origins of the relative barrier heights for the degenerate Cope rearrangements of semibullvalene (1), barbaralane (2), bullvalene (3), and dihydrobullvalene (4). We conclude from our calculations that, of the four transition structures (TSs), that for rearrangement of 1 has the smallest amount of interallylic bonding. Nevertheless, relief of strain in the reactant confers on 1 the lowest barrier to Cope rearrangement. Conjugation between the cyclopropane ring and the pi bond of the etheno bridge in 3 makes the barrier for its Cope rearrangement higher than that for 4 and also contributes to making the barrier for 3 higher than that for 2. However, the relatively low barrier to the Cope rearrangement of 2 is largely due to the TS for this reaction having the largest amount of interallylic bonding of all four TSs.

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PubMed2005

Ligand-assisted reduction of osmium tetroxide with molecular hydrogen via a [3+2] mechanism.

Osmium tetroxide is reduced by molecular hydrogen in the presence of ligands in both polar and nonpolar solvents. In CHCl3 containing pyridine (py) or 1,10-phenanthroline (phen), OsO4 is reduced by H2 to the known Os(VI) dimers L2Os(O)2(mu-O)2Os(O)2L2 (L2 = py2, phen). However, in the absence of ligands in CHCl3 and other nonpolar solvents, OsO4 is unreactive toward H2 over a week at ambient temperatures. In basic aqueous media, H2 reduces OsO4(OH)n(n-) (n = 0, 1, 2) to the isolable Os(VI) complex, OsO2(OH)4(2-), at rates close to that found in py/CHCl3. Depending on the pH, the aqueous reactions are exergonic by deltaG = -20 to -27 kcal mol(-1), based on electrochemical data. The second-order rate constants for the aqueous reactions are larger as the number of coordinated hydroxide ligands increases, k(OsO4) = 1.6(2) x 10(-2) M(-1) s(-1) < k(OsO4(OH)-) = 3.8(4) x 10(-2) M(-1) s(-1) < k(OsO4(OH)2(2-)) = 3.8(4) x 10(-1) M(-1) s(-1). The observation of primary deuterium kinetic isotope effects, k(H2)/k(D2) = 3.1(3) for OsO4 and 3.6(4) for OsO4(OH)-, indicates that the rate-determining step in each case involves H-H bond cleavage. Density functional calculations and thermochemical arguments favor a concerted [3+2] addition of H2 across two oxo groups of OsO4(L)n and argue against H* or H- abstraction from H2 or [2+2] addition of H2 across one Os=O bond. The [3+2] mechanism is analogous to that of alkene addition to OsO4(L)n to form diolates, for which acceleration by added ligands has been extensively documented. The observation that ligands also accelerate H2 addition to OsO4(L)n highlights the analogy between these two reactions.

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PubMed2004

A B3LYP study of the effects of phenyl substituents on 1,5-hydrogen shifts in 3-(Z)-1,3-pentadiene provides evidence against a chameleonic transition structure.

The effects of one or two phenyl substituents on the activation enthalpy for a 1,5-hydrogen shift in 3-(Z)-1,3-pentadiene (1) and on the geometry of the transition structure (TS) have been investigated by B3LYP/6-31G calculations. The phenyl-substituent effects on the experimentally measured activation enthalpies are predicted to be sizable, spanning a range of nearly 10 kcal/mol. However, if differences between steric effects in the transoid isomers of the reactants are factored out by comparing the activation enthalpies in the cisoid conformers, the electronic components of the phenyl-substituent effects on both the barrier heights and the TS geometries are found to be quite modest in size. Unlike the TS in the Cope rearrangement, the TS for a 1,5-hydrogen shift in 1 is not highly variable in nature, and the reason the 1,5-hydrogen shift TS is not chameleonic is discussed.

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PubMed2004

Reactions of sterically congested 1,5-hexadienes: Ab initio and DFT calculations on the competition between cope rearrangements and disrotatory cyclobutene ring-opening reactions of bridged syn-tricyclo[4.2.0.0(2,5)]octa-3,7-dienes.

The thermolytic behavior of four syn-tricyclo[4.2.0.0(2,5)]octa-3,7-dienes, each spanned by four propano bridges (13, 14, 21, and 26), has been investigated by means of calculations at the UB3LYP/ 6-31G* and CASPT2/6-31G levels. These calculations predict that 13 should undergo a degenerate Cope rearrangement (E(A) = 19.6 kcal/mol), whereas the other three C(20)H(24) isomers should prefer a necessarily disrotatory cyclobutene ring-opening reaction. In the case of 14, the ring-opening reaction (E(A) = 27.2 kcal/mol) is concerted and leads directly to 15, a 4-fold bridged cyclooctatetraene. In the ring opening of 21, the 1,6-bridge in the 4-fold bridged bicyclo[4.2.0]octa-2,4,7-triene 31 prevents formation of the corresponding cyclooctatetraene. In the ring opening of 26, the 4-fold bridged bicyclo[4.2.0]octa-2,4,7-triene derivative 36 is predicted to form the corresponding bridged cyclooctatetraene 38, which should undergo bond shift. The results of these calculations are found to be in very good agreement with the results of experiments on these hydrocarbons.

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PubMed2004

Effects of spiroconjugation on the calculated singlet-triplet energy gap in 2,2-dialkoxycyclopentane-1,3-diyls and on the experimental electronic absorption spectra of singlet 1,3-diphenyl derivatives. Assignment of the lowest-energy electronic transition of singlet cyclopentane-1,3-diyls.

The effect of a 2,2-ethylene-ketal functionality on the singlet-triplet energy gap (Delta E(ST)) and on the first electronic transition in singlet cyclopentane-1,3-diyls (1) has been investigated. UDFT calculations predict a significant increase in the preference for a singlet ground state in the diradical with the cyclic ketal at C2 (1g; Delta E(ST) = -6.6 kcal/mol in C(2) symmetry and -7.6 kcal/mol in C(2v) symmetry), compared to the 2,2-dihydroxy- and 2,2-dimethoxy-disubstituted diradicals (1d, Delta E(ST) = -3.6 kcal/mol in C(2) symmetry, and 1e, Delta E(ST) = -3.4 kcal/mol in C(2) symmetry). Spiroconjugation is shown to be responsible for the larger calculated value of absolute value Delta E(ST) in 1g, relative to 1d and 1e. A strong correlation between the calculated values of Delta E(ST) and the computed electronic excitation energies of the singlet diradicals is found for diradicals 1d, 1e, and 1g and for 2,2-difluorocyclopentane-1,3-diyl (1c). A similar correlation between Delta E(ST) and lambda(calcd) is predicted for the corresponding 1,3-diphenylcyclopentane-1,3-diyls 3, and the predicted blue shift in the spectrum of 3g, relative to 3e, has been confirmed by experimental comparisons of the electronic absorption spectra of the annelated derivatives 2c, 2e, and 2g in a glass at 77 K. The wavelength of the first absorption band in the singlet diradicals decreases in the order 2e (lambda(onset) = 650 nm) > 2g (lambda(onset) = 590 nm) > 2c (lambda(onset) = 580 nm). The combination of these computational and experimental results provides a sound basis for reassignment of the first electronic absorption band in singlet diradicals 2c, 2e, and 2g to the excitation of an electron from the HOMO to the LUMO of these 2,2-disubstituted derivatives of cyclopentane-1,3-diyl.

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PubMed2003

DFT calculations on the effects of para substituents on the energy differences between singlet and triplet states of 2,2-difluoro-1,3-diphenylcyclopentane-1,3-diyls.

UB3LYP/6-31g* calculations have been performed on a series of para-substituted 2,2-difluoro-1,3-diphenylcyclopentane-1,3-diyls (4). The singlet is computed to be the ground state for each of the diradicals, regardless of the nature of the para substituents, which range from strongly pi-electron-donating (amino) to strongly pi-electron-withdrawing (nitro). In the symmetrically para-disubstituted diradicals, the size of the singlet-triplet energy gap (Delta E(ST)) increases with the pi-electron-donating ability of the substituents, but in the unsymmetrically substituted diradicals, large values of Delta E(ST) are calculated even when one of the substituents is a pi electron acceptor. The origins of the competitive and cooperative substituent effects, predicted for diradical 4, are discussed in light of the calculated effects of the same substituents on the singlet and triplet states of diradical 6, which lacks the geminal fluorines at C-2 that are present in 4.

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PubMed2003

Study of the chemistry of ortho- and para-biphenylnitrenes by laser flash photolysis and time-resolved IR experiments and by B3LYP and CASPT2 calculations.

The photochemistry of ortho-biphenyl azide (1a) has been studied by laser flash photolysis (LFP), with UV-vis and IR detection of the transient intermediates formed. LFP (266 nm) of 1a in glassy 3-methylpentane at 77 K releases singlet ortho-biphenylnitrene (1b) (lambda(max) = 410 nm, tau = 59 +/- 6 ns), which under these conditions decays cleanly to the lower energy triplet state. In fluid solution at 298 K, 1b rapidly (tau < 10 ns) partitions between formation of isocarbazole (4) (lambda(max) = 430 nm, tau = 70 ns) and benzazirine (1e) (lambda(max) = 305 nm, tau = 12 ns). Isocarbazole 4 undergoes a 1,5-hydrogen shift, with k(H)/k(D) = 3.4 at 298 K to form carbazole 9 and smaller amounts of two other isocarbazoles (7 and 8). Benzazirine 1e ring-opens reversibly to azacycloheptatetraene (1f), which serves as a reservoir for singlet nitrene 1b. Azacycloheptatetraene 1f ultimately forms carbazole 9 on the millisecond time scale by the pathway 1f --> 1e --> 1b --> 4 --> 9. The energies of the transient intermediates and of the transition structures connecting them were successfully predicted by CASPT2/6-31G calculations. The electronic and vibrational spectra of the intermediates, computed by density functional theory, support the assignment of the transient spectra, observed in the formation of 9 from 1a.

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PubMed2003

Carbon tunneling from a single quantum state.

We observed ring expansion of 1-methylcyclobutylfluorocarbene at 8 kelvin, a reaction that involves carbon tunneling. The measured rate constants were 4.0 x 10(-6) per second in nitrogen and 4 x 10(-5) per second in argon. Calculations indicated that at this temperature the reaction proceeds from a single quantum state of the reactant so that the computed rate constant has achieved a temperature-independent limit. According to calculations, the tunneling contribution to the rate is 152 orders of magnitude greater than the contribution from passage over the barrier. We discuss environmental effects of the solid-state inert-gas matrix on the reaction rate.

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PubMed2002

Are 1,5-disubstituted semibullvalenes that have C2v equilibrium geometries necessarily bishomoaromatic?

Unrestricted density functional theory (UB3LYP), CASSCF, and CASPT2 calculations have been employed to compute the relative energies of the C(s) and C(2v) geometries of several 1,5-disubstituted semibullvalenes. Substitution at these positions with R = F, -CH(2)-, or -O- affords semibullvalenes that are predicted to have C(2v) equilibrium geometries. Calculated singlet-triplet energy splittings and the energies of isodesmic reactions are used to assess the amount of bishomoaromatic character at these geometries. The results of these calculations show that employing strain to destabilize the C(s) geometries of semibullvalenes can lead to a significant decrease in the amount of bishomoaromatic stabilization of the C(2v) geometries, due to reduced through-space interaction between the two allyl groups. However, the C(2v) equilibrium geometries of the 1,5-disubstituted semibullvalenes with R = F and -RR- = -O- do benefit from stabilizing through-bond interactions between the two allyl groups. These interactions involve mixing of the bisallyl HOMO with the low-lying C-F or C-O sigma orbital combinations of the same symmetry. In contrast, for -RR- = -CH(2)-, through-bond interactions destabilize the bisallyl HOMO and are predicted to make the ground state of this semibullvalene a triplet.

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