Like (CO)4, Do (CS)4 and (CSe)4 Have a Triplet Ground State?

Cyclobutane‐1,2,3,4‐tetraone, (CO)₄, was computationally predicted and, subsequently, experimentally confirmed to have a triplet ground state, in which a b_2g σ MO and an a_2u π MO were each singly occupied. In contrast, the (U)CCSD(T) calculations reported herein found that cyclobutane‐1,2,3,4‐tetrathione, (CS)₄, and cyclobutane‐1,2,3,4‐tetraselenone, (CSe)₄, both had singlet ground states, in which the b_2g σ MO was doubly occupied and the a_2u π MO was empty. Our calculations showed that both the longer C?X distances and smaller coefficients on the carbon atoms in the b_2g and a_2u MOs of (CS)₄ and (CSe)₄ contributed to the difference between the ground states of these two molecules and the ground state of (CO)₄. An experimental test of the prediction of a singlet ground state for (CS)₄ is proposed.     

Heavy‐Atom Tunneling in the Ring Opening of a Strained Cyclopropene at Very Low Temperatures

The highly strained 1H‐bicyclo[3.1.0]‐hexa‐3,5‐dien‐2‐one 1 is metastable, and rearranges to 4‐oxacyclohexa‐2,5‐dienylidene 2 in inert gas matrices (neon, argon, krypton, xenon, and nitrogen) at temperatures as low as 3 K. The kinetics for this rearrangement show pronounced matrix effects, but in a given matrix, the reaction rate is independent of temperature between 3 and 20 K. This temperature independence means that the activation energy is zero in this temperature range, indicating that the reaction proceeds through quantum mechanical tunneling from the lowest vibrational level of the reactant. At temperatures above 20 K, the rate increases, resulting in curved Arrhenius plots that are also indicative of thermally activated tunneling. These experimental findings are supported by calculations performed at the CASSCF and CASPT2 levels by using the small‐curvature tunneling (SCT) approximation.     

Surface phase behavior and microstructure of lipid/PEG-emulsifier monolayer-coated microbubbles

Langmuir trough methods and fluorescence microscopy were combined to investigate the phase behavior and microstructure of monolayer shells coating micron-scale bubbles (microbubbles) typically used in biomedical applications. The monolayer shell consisted of a homologous series of saturated acyl chain phospholipids and an emulsifier containing a single hydrophobic stearate chain and polyethylene glycol (PEG) head group. PEG-emulsifier was fully miscible with expanded phase lipids and phase separated from condensed phase lipids. Phase coexistence was observed in the form of dark condensed phase lipid domains surrounded by a sea of bright, emulsifier-rich expanded phase. A rich assortment of condensed phase area fractions and domain morphologies, including networks and other novel structures, were observed in each batch of microbubbles. Network domains were reproduced in Langmuir monolayers under conditions of heating–cooling followed by compression–expansion, as well as in microbubble shells that underwent surface flow with slight compression. Domain size decreased with increased cooling rate through the phase transition temperature, and domain branching increased with lipid acyl chain length at high cooling rates. Squeeze-out of the emulsifier at a surface pressure near 35 mN/m was indicated by a plateau in Langmuir isotherms and directly visualized with fluorescence microscopy, although collapse of the solid lipid domains occurred at much higher surface pressures. Compression of the monolayer past the PEG-emulsifier squeeze-out surface pressure resulted in a dark shell composed entirely of lipid. Under certain conditions, the PEG-emulsifier was reincorporated upon subsequent expansion. Factors that affect shell formation and evolution, as well as implications for the rational design of microbubbles in medical applications, are discussed.     

Do deviations from bond enthalpy additivity define the thermodynamic stabilities of diradicals?

Deviations from bond enthalpy additivity (DeltaBEA) are frequently used to assess the thermodyamic stabilities of diradicals. (U)B3LYP/6-31G calculations have been performed in order to determine how well DeltaBEA values actually do reflect the thermodynamic stabilities of the triplet states of diradicals in which one or both nonbonding electrons occupy a delocalized pi orbital. The calculations find that different pathways for forming sigma,pi-diradicals, such as alpha,2- and alpha,4-dehydrotoluene (4 and 6), give DeltaBEA values that differ by ca. 1 kcal/mol. The path dependency of the DeltaBEA values is computed to be one order of magnitude larger for non-Kekulé hydrocarbon diradicals, such as m-benzoquinodimethane (12) and 1,3-dimethylenecyclobutane-2,4-diyl (15), than for sigma,pi-diradicals. Since the DeltaBEA values for forming 4, 6, 12, and 15 are all path dependent, we conclude that DeltaBEA values for diradicals with one or two delocalized, nonbonding pi electrons do not, in general, uniquely define the thermodynamic stabilities of the diradicals. Hence, DeltaBEA values should not be used for this purpose, especially for non-Kekulé hydrocarbon diradicals.     

Structure and torsional flexibility of the linkage between guanine and fluorene residues in the deoxyguanosine–aminofluorene and deoxyguanosine–acetylaminofluorene carcinogenic adducts

Potential energy surfaces for rotations around two central CN bonds in N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF–dG) and its deacetylated derivative (AF–dG) were studied using Amber 95 molecular mechanics. Both of these adducts are known to be strong mutagens and carcinogens. New Amber 95 force field parameters were derived for the linkage connecting guanine and fluorene moieties in AAF–dG and AF–dG. For this purpose, we determined ab initio MP2/cc-pVDZ//B3-LYP/6-31G* and polarized continuum model Hartree–Fock/6-31G* potential energy surfaces of smaller model systems that included the N-methylimidazole–acetylaniline and N-methylimidazole–aniline adducts. The molecular mechanics parameters were adjusted to minimize differences between the gas-phase ab initio and molecular mechanics surfaces of these model systems. The resulting parameters were transferred to AF–dG and AAF–dG. The barrier for the rotation of the fluorene residue in AF–dG was found to be less than 2 kcal/mol. Such a small barrier renders the fluorene moiety freely rotatable at room temperature. In contrast, the fluorene rotation in AAF–dG is hindered by a significantly larger barrier of 10 kcal/mol. This barrier corresponds to conformations in which the fluorene and acetyl groups lie in the same plane, and is largely due to steric repulsion. Similarly, the coplanar arrangement of guanine and the bridging amino or acetyl groups is disfavored by 5–10 kcal/mol, with AAF–dG again being the more rigid of the two molecules. Energy minima for a rotation around a bond between guanine and the bridging nitrogen are found at ±80° in AAF–dG, and at 120° and –90° for AF–dG. Overall, the fluorene–dG linkages in AF–dG and AAF–dG adducts have significantly different equilibrium structures and torsional flexibilities. These differences may be contributing factors for the observed disparity in mutagenic effects of these adducts.Electronic Supplementary Material: Supplementary material is available in the online version of this article at Acknowledgements. This work was supported by the NSF REU grant no. CHE-0243825 to Loyola University Chicago. We thank to Tom Ellenberger and Shuchismita Dutta for providing us with their results prior to publication.     

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.     

Chelation of vanadium(V) by difluoromethylene bisphosphonate, a structural analogue of pyrophosphate

The structural and functional analogy between difluoromethylene bisphosphonate (CF2PP) and pyrophosphate (PPi) is investigated in a reaction with V(V) in the form of vanadate. The reaction of CF2PP with vanadate was investigated using 1.00 M KCl as supporting electrolyte over the ranges 3 < or = [CF2PP] < or = 60 mM and 2.06 < or = pH < or = 11.80. 51V, 19F, and 31P NMR spectroscopic studies showed that a 1:1 species was formed with an H+-dependent formation constant of 110 M-1 at pH 7.22. Results of solution experiments and ab initio calculations are consistent with CF2PP coordinating V(V) in a bidentate manner, as previously reported for PPi. Below pH 4, a minor complex forms, which is consistent with a 1:2 stoichiometry. This complex was also observed with pyrophosphate. The X-ray crystal structure of the monoprotonated difluoromethylene bisphosphonate anion (H[CF2PP]3-)-toludine complex is presented. The H[CF2PP]3- anion crystallized in the triclinic space group P with a = 12.7629(7) A, b = 13.3992(7) A, c = 17.1002(9) A, and V = 2584.4(2) A3, and Z = 2. Sheets of the layers of anions are connected through a network of H-bonds and separated by a layer of toludine cations. The structural features are investigated, and the CF2PP anion was found to be longer and wider than the corresponding PPi. Given the larger size of this anion compared to PPi, the chelation affinity upon CF2 substitution was found to be 4-5-fold reduced at neutral pH.