Reaction blockading in a reaction between an excited atom and a charged molecule at low collision energy.

Recent advances have enabled studies of atom-ion chemistry at unprecedentedly low temperatures, allowing precision observation of chemical reactions and novel chemical dynamics. So far, these studies have primarily involved reactions between atoms and atomic ions or non-polar molecular ions, often in their electronic ground state. Here, we extend this work by studying an excited atom-polar-molecular-ion chemical reaction (Ca* + BaCl+) at low temperature in a hybrid atom-ion trapping system. The reaction rate and product branching fractions are measured and compared to model calculations as a function of both atomic quantum state and collision energy. At the lowest collision energy we find that the chemical dynamics differ dramatically from capture theory predictions and are primarily dictated by the radiative lifetime of the atomic quantum state instead of the underlying excited-state interaction potential. This reaction blockading effect, which greatly suppresses the reactivity of short-lived excited states, provides a means for directly probing the reaction range and also naturally suppresses unwanted chemical reactions in hybrid trapping experiments.

Synthesis of mixed hypermetallic oxide BaOCa+ from laser-cooled reagents in an atom-ion hybrid trap.

Hypermetallic alkaline earth (M) oxides of formula MOM have been studied under plasma conditions that preclude insight into their formation mechanism. We present here the application of emerging techniques in ultracold physics to the synthesis of a mixed hypermetallic oxide, BaOCa+ These methods, augmented by high-level electronic structure calculations, permit detailed investigation of the bonding and structure as well as the mechanism of its formation via the barrierless reaction of Ca (3PJ) with BaOCH3+ Further investigations of the reaction kinetics as a function of collision energy over the range 0.005 kelvin (K) to 30 K and of individual Ca fine-structure levels compare favorably with calculations based on long-range capture theory.

Predictive coupled-cluster isomer orderings for some SinCm (m, n ≤ 12) clusters: A pragmatic comparison between DFT and complete basis limit coupled-cluster benchmarks.

The accurate determination of the preferred Si12C12 isomer is important to guide experimental efforts directed towards synthesizing SiC nano-wires and related polymer structures which are anticipated to be highly efficient exciton materials for the opto-electronic devices. In order to definitively identify preferred isomeric structures for silicon carbon nano-clusters, highly accurate geometries, energies, and harmonic zero point energies have been computed using coupled-cluster theory with systematic extrapolation to the complete basis limit for set of silicon carbon clusters ranging in size from SiC3 to Si12C12. It is found that post-MBPT(2) correlation energy plays a significant role in obtaining converged relative isomer energies, suggesting that predictions using low rung density functional methods will not have adequate accuracy. Utilizing the best composite coupled-cluster energy that is still computationally feasible, entailing a 3-4 SCF and coupled-cluster theory with singles and doubles extrapolation with triple-ζ (T) correlation, the closo Si12C12 isomer is identified to be the preferred isomer in the support of previous calculations [X. F. Duan and L. W. Burggraf, J. Chem. Phys. 142, 034303 (2015)]. Additionally we have investigated more pragmatic approaches to obtaining accurate silicon carbide isomer energies, including the use of frozen natural orbital coupled-cluster theory and several rungs of standard and double-hybrid density functional theory. Frozen natural orbitals as a way to compute post-MBPT(2) correlation energy are found to be an excellent balance between efficiency and accuracy.

At what chain length do unbranched alkanes prefer folded conformations?

Short unbranched alkanes are known to prefer linear conformations, whereas long unbranched alkanes are folded. It is not known with certainty at what chain length the linear conformation is no longer the global minimum. To clarify this point, we use ab initio and density functional methods to compute the relative energies of the linear and hairpin alkane conformers for increasing chain lengths. Extensive electronic structure calculations are performed to obtain optimized geometries, harmonic frequencies, and accurate single point energies for the selected alkane conformers from octane through octadecane. Benchmark CCSD(T)/cc-pVTZ single point calculations are performed for chains through tetradecane, whereas approximate methods are required for the longer chains up to octadecane. Using frozen natural orbitals to unambiguously truncate the virtual orbital space, we are able to compute composite CCSD FNO(T) single point energies for all the chain lengths. This approximate composite method has significant computational savings compared to full CCSD(T) while retaining ∼0.15 kcal/mol accuracy compared to the benchmark results. More approximate dual-basis resolution-of-the-identity double-hybrid DFT calculations are also performed and shown to have reasonable 0.2-0.4 kcal/mol errors compared with our benchmark values. After including contributions from temperature dependent internal energy shifts, we find the preference for folded conformations to lie between hexadecane and octadecane, in excellent agreement with recent experiments [ Lüttschwager , N. O. ; Wassermann , T. N. ; Mata , R. A. ; Suhm , M. A. Angew. Chem. Int. Ed. 2013 , 52 , 463 ].

Controllable binding of polar molecules and metastability of one-dimensional gases with attractive dipole forces.

We explore one-dimensional samples of ultracold polar molecules with attractive dipole-dipole interactions and show the existence of a repulsive barrier caused by a strong quadrupole interaction between molecules. This barrier can stabilize a gas of ultracold KRb molecules and even lead to long-range wells supporting bound states between the molecules. The properties of these wells can be controlled by external electric fields, allowing the formation of long polymerlike chains of KRb and studies of quantum phase transitions by varying the effective interaction between molecules. We discuss the generalization of those results to other systems.

Structure, energetics, and reactions of alkali tetramers.

Electronic structure calculations have been carried out for all possible alkali tetramers that can be formed from X(2) + X(2) → X(2)X(2), X(2) + Y(2) → X(2)Y(2), and XY + XY → X(2)Y(2) alkali dimer association reactions. Vibrationally stable rhombic (D(2h)) and planar (C(s)) structures are found for all possible tetramers formed from the alkali metals, Li to Cs. All tetramer formation reactions (from ground state singlet homonuclear or heteronuclear dimers) are found to be exothermic with binding energies ranging from 6282 cm(-1) for Li(2)Li(2) to 1985 cm(-1) for Cs(2)Cs(2). Extensive calculations, carried out at long-range for several reactant pairs, indicate that there are barrier-less pathways for the formation of tetramers from dimer association reactions. At low temperatures, direct formation of tetramers is unlikely, owing to the large exothermicity associated with these association reactions, but atom exchange reactions (X(2) + Y(2) ↔ XY + XY) are possible for some species.

Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides.

A series of C-6 alkyl, cycloalkyl, and aryl-9-(ß-d-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia coli purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph(3)P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-ß-d-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH(3)/MeOH gave the corresponding 6-alkyl-9-(ß-d-ribofuranosyl)purine derivatives 7-11, respectively, in good yields. Reactions of 6 with cycloalkyl(propyl, butyl, pentyl)zinc halides and aryl (phenyl, 2-thienyl)zinc halides gave under similar conditions the corresponding 6-cyclopropyl, cyclobutyl, cyclopentyl, phenyl, and thienyl -9-(ß-d-ribofuranosyl)purine derivatives 12-16, respectively in high yields. E. coli PNP showed a high tolerance to the steric and hydrophobic environment at the 6-position of the synthesized purine ribonucleosides. Significant cytotoxic activity was observed for 8, 12, 15, and 16. Evaluation of 12 and 16 against human tumor xenografts in mice did not demonstrate any selective antitumor activity. In addition, 6-methyl-9-(ß-d-arabinofuranosyl)purine (18) was prepared and evaluated.

Long-range interactions between like homonuclear alkali metal diatoms.

Long-range electrostatic and van der Waals coefficients up to terms of order R(-8) have been evaluated by the sum over states method using ab initio and time-dependent density functional theory. We employ several widely used density functionals and systematically investigate the convergence of the calculated results with basis set size. Static electric moments and polarizabilities up to octopole order are also calculated. We present values for Li(2) through K(2) which are in good agreement with existing values, in addition to new results for Rb(2) and Cs(2). Interaction potential curves calculated from these results are shown to agree well with high level ab initio theory. Preliminary results are reported that demonstrate the applicability of the method to larger alkali clusters.

Long range intermolecular interactions between the alkali diatomics Na(2), K(2), and NaK.

Long range interactions between the ground state alkali diatomics Na(2)-Na(2), K(2)-K(2), Na(2)-K(2), and NaK-NaK are examined. Interaction energies are first determined from ab initio calculations at the coupled-cluster with singles, doubles, and perturbative triples [CCSD(T)] level of theory, including counterpoise corrections. Long range energies calculated from diatomic molecular properties (polarizabilities and dipole and quadrupole moments) are then compared with the ab initio energies. A simple asymptotic model potential E(LR)=E(elec)+E(disp)+E(ind) is shown to accurately represent the intermolecular interactions for these systems at long range.

Rotational spectrum, tunneling motions, and potential barriers of benzyl alcohol.

The rotational spectra of benzyl alcohol and of its OD isotopologue have been assigned and measured in a supersonic expansion, either with pulsed-jet Fourier transform microwave or free jet absorption millimeter wave spectroscopy. The spectrum is consistent with a gauche conformation of the oxygen atom, characterized by a theta (OC(7)-C(1)C(2)) dihedral angle of approximately 55 degrees. Such a configuration is 4-fold degenerate, corresponding to minima with theta approximately +/-60 degrees, +/-120 degrees. The four equivalent minima are separated by two kinds of barrier, corresponding to theta = +/-90 degrees, and 0 or 180 degrees. Only the theta = +/-90 degrees barriers are low enough to generate a tunneling splitting, which has been measured in a spectrum strongly perturbed by tunneling interactions. The observed splittings diminish considerably upon deuterium substitution. The tunneling splittings are consistent with a barrier about 280 cm(-1) and high level ab initio calculations predicting a 320 cm(-1) barrier.

Helical C(2) structure of perfluoropentane and the C(2v) structure of perfluoropropane.

Saturated hydrocarbons have structures with completely staggered bonds and dihedral angles of 180 degrees . Substituting hydrogen by fluorine results in a slight shift from 180 degrees , giving rise to a helical structure. X-ray diffraction studies on fibers and computational studies on perfluoroalkanes estimate a dihedral angle of about 17 degrees from the trans position. The rotational spectra of perfluoropentane and its three (13)C isotopomers have been observed and assigned using a pulsed-jet Fourier transform microwave spectrometer. The rotational constants for the parent species are A 990.6394(3) MHz, B 314.0002(1) MHz, and C 304.3703(1) MHz, respectively. The determination of an exact dihedral angle has been challenging, as the helical twist has proven to be quite sensitive to the structural inputs and constraints. A series of r(0) structures incorporating various model constraints and a Kraitchman analysis gives a range of 13-19 degrees for the torsional angle. An objective approach, which only assumes overall C(2) symmetry, is to scale the principal coordinates from ab initio models by the square root of the ratio of the observed second moments to the computed second moments. The scaled structures of computed models at various levels of theory reproduce the parent second moments exactly and the (13)C second moments very well, giving a dihedral angle of 17 +/- 1 degrees from trans. The microwave spectrum of perfluoropropane has also been observed and assigned. The rotational constants are A 1678.5982(9) MHz, B 900.1968(10) MHz, and C 955.3216(11) MHz, respectively. Unlike longer perfluoroalkanes, perfluoropropane has a nonhelical, C(2v) structure. Computations are in excellent agreement with experimental results.

Unrestricted Coupled Cluster and Brueckner Doubles Variations of W1 Theory.

Unrestricted coupled cluster spin contamination corrected [UCCSD(T)] and unrestricted Brueckner doubles [UBD(T)] variations of the Weizmann-1 theory (W1), denoted as W1U, W1Usc, and W1BD, respectively, are compared with the restricted open-shell W1 theory [W1(RO)]. The performances of the four W1 variants are assessed with 220 total atomization energies, electron affinities, ionization potentials, and proton affinities in the G2/97 test set, for consistency with the error analysis of the original W1(RO) study. The root-mean-square deviations from the experiment of W1U (0.65 ± 0.48 kcal/mol), W1Usc (0.57 ± 0.48 kcal/mol), W1BD (0.62 ± 0.48 kcal/mol), and W1(RO) (0.57 ± 0.48 kcal/mol) show that the four methods are virtually indistinguishable. This error analysis excludes the "singlet biradicals," C2 and O3, since single determinantal methods are not really adequate for these strongly multireference systems. The unrestricted W1 variants perform poorly for such highly spin-contaminated and multireference species (the largest deviation from experiment for W1Usc is -4.2 ± 0.1 kcal/mol for the O3 EA). W1(RO) performs much better than its unrestricted counterparts for these pathological cases (the deviation from experiment is reduced to -1.5 ± 0.1 kcal/mol for the O3 EA), though the errors are significantly larger than those for the overall test set. The examples of C2, O3, and the F2 potential energy curve indicate that an advantage to using W1BD is that the error in ⟨S(2)⟩ correlates with the magnitude of the error in energy, whereas W1(RO) loses accuracy without such a warning.

A restricted-open-shell complete-basis-set model chemistry.

A restricted-open-shell model chemistry based on the complete basis set-quadratic Becke3 (CBS-QB3) model is formulated and denoted ROCBS-QB3. As the name implies, this method uses spin-restricted wave functions, both for the direct calculations of the various components of the electronic energy and for extrapolating the correlation energy to the complete-basis-set limit. These modifications eliminate the need for empirical corrections that are incorporated in standard CBS-QB3 to compensate for spin contamination when spin-unrestricted wave functions are used. We employ an initial test set of 19 severely spin-contaminated species including doublet radicals and both singlet and triplet biradicals. The mean absolute deviation (MAD) from experiment for the new ROCBS-QB3 model (3.6+/-1.5 kJ mol(-1)) is slightly smaller than that of the standard unrestricted CBS-QB3 version (4.8+/-1.5 kJ mol(-1)) and substantially smaller than the MAD for the unrestricted CBS-QB3 before inclusion of the spin correction (16.1+/-1.5 kJ mol(-1)). However, when applied to calculate the heats of formation at 298 K for the moderately spin-contaminated radicals in the G2/97 test set, ROCBS-QB3 does not perform quite as well as the standard unrestricted CBS-QB3, with a MAD from experiment of 3.8+/-1.6 kJ mol(-1) (compared with 2.9+/-1.6 kJ mol(-1) for standard CBS-QB3). ROCBS-QB3 performs marginally better than standard CBS-QB3 for the G2/97 set of ionization energies with a MAD of 4.1+/-0.1 kJ mol(-1) (compared with 4.4+/-0.1 kJ mol(-1)) and electron affinities with a MAD of 3.9+/-0.2 kJ mol(-1) (compared with 4.3+/-0.2 kJ mol(-1)), but the differences in MAD values are comparable to the experimental uncertainties. Our overall conclusion is that ROCBS-QB3 eliminates the spin correction in standard CBS-QB3 with no loss in accuracy.

Combining Quantum Mechanics Methods with Molecular Mechanics Methods in ONIOM.

The purpose of this paper is 2-fold. First, we present several extensions to the ONIOM(QM:MM) scheme. In its original formulation, the electrostatic interaction between the regions is included at the classical level. Here we present the extension to electronic embedding. We show how the behavior of ONIOM with electronic embedding can be more stable than QM/MM with electronic embedding. We also investigate the link atom correction, which is implicit in ONIOM but not in QM/MM. Second, we demonstrate some of the practical aspects of ONIOM(QM:MM) calculations. Specifically, we show that the potential surface can be discontinuous when there is bond breaking and forming closer than three bonds from the MM region.

Synthesis and biological activity of 4'-thio-L-xylofuranosyl purine nucleosides.

A series of some new 4'-thio-L-xylofuranosyl nucleosides were prepared and evaluated as potential anticancer agents. A versatile sugar intermediate for direct coupling with the purine moiety is also synthesized by an efficient and high-yielding route. Proof of structure and configuration at all chiral centers of the nucleosides was obtained by proton NMR. All target compounds were evaluated in a series of human cancer cell lines in vitro. The details of the synthesis of the carbohydrate precursor 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-L-xylofuranose (6) and corresponding purine nucleosides are presented in the manuscript.

Selective metalation of 6-methylpurines: synthesis of 6-fluoromethylpurines and related nucleosides.

A selective metalation at the 6-CH3 over C-8 of 6-methylpurine derivative 6 was observed with softer counter cation (Na+ or K+) of the base, while the harder Li+ showed no selectivity. In the presence of N-fluorobenzenesulfonamide (NFSI), this property was utilized for the synthesis of 6-fluoromethylpurine derivatives 4 and 5 as potential toxins for suicide gene therapy.

Preclinical antitumor activity of 4'-thio-beta-D-arabinofuranosylcytosine (4'-thio-ara-C).

PURPOSE: 4'-Thio-beta -d-arabinofuranosylcytosine (4'-thio-ara-C), which has shown significant cytotoxicity against a panel of human tumor lines, was evaluated for antitumor activity against a spectrum of human tumor systems in mice. METHODS: Antitumor activity was evaluated in 15 subcutaneously implanted human tumor xenografts. 4'-Thio-ara-C was administered intraperitoneally using either q1dx9 (daily treatment for nine consecutive days) or q4hx3/q1dx9 (three treatments each day separated by 4-h intervals for nine consecutive days). RESULTS: 4'-Thio-ara-C exhibited an excellent spectrum of activity. Treatment with the compound was curative against HCT-116 colon, SW-620 colon, NCI-H23 NSCL, and CAKI-1 renal tumors and resulted in partial/complete regressions in the DLD-1 colon, NCI-H522 NSCL, DU-145 prostate, and PANC-1 pancreatic tumor models. Tumor stasis was noted for HT29 colon and NCI-H460 NSCL tumors. Tumor inhibition was observed for A549 NSCL, PC-3 prostate, LNCAP prostate, and MDA-MB-435 breast tumors. Of the 15 tumors examined, only CFPAC-1 pancreatic was unresponsive to the compound. In contrast, 1-beta -d-arabinofuranosylcytosine was minimally active at best against CAKI-1 renal, HCT-116 colon, NCI-H460 NSCL, and SW-620 colon tumors. Schedule- and route-dependency studies were conducted using the NCI-H460 NSCL tumor. The activity of 4'-thio-ara-C was independent of schedule when comparing q2dx5 (every other day for five treatments), q1dx9, and q4hx3/q1dx9 treatment schedules. 4'-Thio-ara-C was equally effective by the intravenous and intraperitoneal routes of administration, with the oral route being less efficacious. CONCLUSIONS: On the basis of these results, 4'-thio-ara-C appears to have a profile distinct from other nucleoside antitumor agents and is being advanced to clinical trials.

Synthesis and anti-cancer activity of some novel 5-azacytosine nucleosides.

1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine to obtain alpha and beta anomers of nucleosides. All four nucleosides were reduced to the corresponding dihydro derivatives and deblocked to give target compounds. All eight target compounds were evaluated in a series of human cancer cell lines in culture. Only 2'-deoxy-4'-thio-5-azacytidine (3beta) was found to be cytotoxic in all the cell lines and was further evaluated in vivo. Details of the synthesis and biological activity are reported.

Enhancement of nucleoside cytotoxicity through nucleotide prodrugs.

A common reason for the lack of cytotoxicity of certain nucleosides is thought to be their inability to be initially activated to the monophosphate level by a nucleoside kinase or other activating enzyme. In a search for other nucleosides that might be worthwhile anticancer agents, we have begun to examine the utilization of monophosphate prodrugs in order to explore whether any enhanced cytotoxicity might be found for the prodrugs of candidate nucleosides that have little or no cytotoxicity. To that end, 5'-bis(pivaloyloxymethyl) phosphate prodrugs of two weakly cytotoxic compounds, 8-aza-2'-deoxyadenosine (5) and 8-bromo-2'-deoxyadenosine (9), have been prepared. These prodrugs (8 and 12) were examined for their cytotoxicity in CEM cells and were found to possess significantly enhanced cytotoxicity when compared with the corresponding parent nucleosides. Further cell culture experiments were conducted to gain insight into the mechanisms of cytotoxicity of these two prodrugs, and those data are reported.