The preparation and properties of neutral diamide ionophores for group IIa metal cations

The preparation of a series of neutral ligands featuring ether and N-methyl-N-carbethoxypentylamide groups is described. These ligands as well as related ones bearing other diamide groups are shown to selectively chelate Group IIA cations by picrate extraction from water to methylene chloride. The changes in UV absorption of aromatic rings and amide groups in the ligands upon titration with metal salts in methanol allow the estimation of the stoichiometry of complexation and the ordering of cation binding. The observed selectivity sequences of cation extraction and binding are briefly discussed. Preliminary proton and ¹³C NMR studies on the effect of addition of Group IIA cation salts to several of the ligands in methanol suggest that most of the complexation occurs at the central ether and amide groups. ¹³C NMR T₁ changes by the Inversion Recovery Fourier Transform method are in agreement with the cation-induced shift data.     

Combining smart darting with parallel tempering using Eckart space: application to Lennard-Jones clusters

The smart-darting algorithm is a Monte Carlo based simulation method used to overcome quasiergodicity problems associated with disconnected regions of configurations space separated by high energy barriers. As originally implemented, the smart-darting method works well for clusters at low temperatures with the angular momentum restricted to zero and where there are no transitions to permutational isomers. If the rotational motion of the clusters is unrestricted or if permutational isomerization becomes important, the acceptance probability of darting moves in the original implementation of the method becomes vanishingly small. In this work the smart-darting algorithm is combined with the parallel tempering method in a manner where both rotational motion and permutational isomerization events are important. To enable the combination of parallel tempering with smart darting so that the smart-darting moves have a reasonable acceptance probability, the original algorithm is modified by using a restricted space for the smart-darting moves. The restricted space uses a body-fixed coordinate system first introduced by Eckart, and moves in this Eckart space are coupled with local moves in the full 3N-dimensional space. The modified smart-darting method is applied to the calculation of the heat capacity of a seven-atom Lennard-Jones cluster. The smart-darting moves yield significant improvement in the statistical fluctuations of the calculated heat capacity in the region of temperatures where the system isomerizes. When the modified smart-darting algorithm is combined with parallel tempering, the statistical fluctuations of the heat capacity of a seven-atom Lennard-Jones cluster using the combined method are smaller than parallel tempering when used alone.     

Broken-symmetry unrestricted hybrid density functional calculations on nickel dimer and nickel hydride

In the present work we investigate the adequacy of broken-symmetry unrestricted density functional theory for constructing the potential energy curve of nickel dimer and nickel hydride, as a model for larger bare and hydrogenated nickel cluster calculations. We use three hybrid functionals: the popular B3LYP, Becke's newest optimized functional Becke98, and the simple FSLYP functional (50% Hartree-Fock and 50% Slater exchange and LYP gradient-corrected correlation functional) with two basis sets: all-electron (AE) Wachters+f basis set and Stuttgart RSC effective core potential (ECP) and basis set. We find that, overall, the best agreement with experiment, comparable to that of the high-level CASPT2, is obtained with B3LYP/AE, closely followed by Becke98/AE and Becke98/ECP. FSLYP/AE and B3LYP/ECP give slightly worse agreement with experiment, and FSLYP/ECP is the only method among the ones we studied that gives an unacceptably large error, underestimating the dissociation energy of Ni(2) by 28%, and being in the largest disagreement with the experiment and the other theoretical predictions. We also find that for Ni(2), the spin projection for the broken-symmetry unrestricted singlet states changes the ordering of the states, but the splittings are less than 10 meV. All our calculations predict a deltadelta-hole ground state for Ni(2) and delta-hole ground state for NiH. Upon spin projection of the singlet state of Ni(2), almost all of our calculations: Becke98 and FSLYP both AE and ECP and B3LYP/AE predict (1)(d(A)(x(2)-y(2)d(B)(x(2)-y(2)) or (1)(d(A)(xy) (d)(B)(xy)) ground state, which is a mixture of (1)Sigma(g) (+) and (1)Gamma(g). B3LYP/ECP predicts a (3)(d(A)(x(2)-y(2))d(B)(xy) (mixture of (3)Sigma(g) (-) and (3)Gamma(u)) ground state virtually degenerate with the (1)(d(A)(x(2)-y(2)d(B)(x)(2)-y(2)/(1)(d(A)(xy)D(B)(xy) state. The doublet delta-hole ground state of NiH predicted by all our calculations is in agreement with the experimentally predicted (2)Delta ground state. For Ni(2), all our results are consistent with the experimentally predicted ground state of 0(g) (+) (a mixture of (1)Sigma(g) (+) and (3)Sigma(g) (-)) or 0(u) (-) (a mixture of (1)Sigma(u) (-) and (3)Sigma(u) (+)).     

The first experimental test of the hypothesis that enzymes have evolved to enhance hydrogen tunneling

The literature hypothesis that "the optimization of enzyme catalysis may entail the evolutionary implementation of chemical strategies that increase the probability of quantum-mechanical tunneling" is experimentally tested herein for the first time. The system employed is the key to being able to provide this first experimental test of the "enhanced hydrogen tunneling" hypothesis, one that requires a comparison of the three criteria diagnostic of tunneling (vide infra) for the same, or nearly the same, reaction with and without the enzyme. Specifically, studied herein are the adenosylcobalamin (AdoCbl, also known as coenzyme B(12))-dependent diol dehydratase model reactions of (i). H(D)(*) atom abstraction from ethylene glycol-d(0) and ethylene glycol-d(4) solvent by 5'-deoxyadenosyl radical (Ado(*)) and (ii.) the same H(*) abstraction reactions by the 8-methoxy-5'-deoxyadenosyl radical (8-MeOAdo(*)). The Ado(*) and 8-MeOAdo(*) radicals are generated by Co-C thermolysis of their respective precursors, AdoCbl and 8-MeOAdoCbl. Deuterium kinetic isotope effects (KIEs) of the H(*)(D(*)) abstraction reactions from ethylene glycol have been measured over a temperature range of 80-120 degrees C: KIE = 12.4 +/- 1.1 at 80 degrees C for Ado(*) and KIE = 12.5 +/- 0.9 at 80 degrees C for 8-MeOAdo(*) (values ca. 2-fold that of the predicted maximum primary times secondary ground-state zero-point energy (GS-ZPE) KIE of 6.4 at 80 degrees C). From the temperature dependence of the KIEs, zero-point activation energy differences ([E(D) - E(H)]) of 3.0 +/- 0.3 kcal mol(-)(1) for Ado(*) and 2.1 +/- 0.6 kcal mol(-)(1) for 8-MeOAdo(*) have been obtained, both of which are significantly larger than the nontunneling, zero-point energy only maximum of 1.2 kcal mol(-)(1). Pre-exponential factor ratios (A(H)/A(D)) of 0.16 +/- 0.07 for Ado(*) and 0.5 +/- 0.4 for 8-MeOAdo(*) are observed, both of which are significantly less than the 0.7 minimum for nontunneling behavior. The data provide strong evidence for the expected quantum mechanical tunneling in the Ado(*) and 8-MeOAdo(*)-mediated H(*) abstraction reactions from ethylene glycol. More importantly, a comparison of these enzyme-free tunneling data to the same KIE, (E(D) - E(H)) and A(H)/A(D) data for a closely related, Ado(*)-mediated H(*) abstraction reaction from a primary CH(3)- group in AdoCbl-dependent methylmalonyl-CoA mutase shows the enzymic and enzyme-free data sets are identical within experimental error. The Occam's Razor conclusion is that at least this adenosylcobalamin-dependent enzyme has not evolved to enhance quantum mechanical tunneling, at least within the present error bars. Instead, this B(12)-dependent enzyme simply exploits the identical level of quantum mechanical tunneling that is available in the enzyme-free, solution-based H(*) abstraction reaction. The results also require a similar, if not identical, barrier width and height within experimental error for the H(*) abstraction both within, and outside of, the enzyme.     

High-throughput purification of combinatorial libraries II: Automated separation of single diastereomers from a 4-amido-pyrrolidone library containing intentional diastereomer pairs

A 4-amido-pyrrolidone library that was intentionally synthesized as pairs of diastereomers was produced by solution-phase parallel syntheses and purified by an automated high-throughput purification system. A total of 2592 4-amido-pyrrolidinones were ultimately isolated as single diastereomers from a matrix of 1920 syntheses. After the four-step synthesis and HPLC purification, the average yield of a single diastereomer was 36.6%. The average chemical purity was >90%, and the average diastereomeric purity was >87%. The choice of chiral amines used to make amides with heterocyclic acid chlorides had a dramatic effect on success. Analysis of the relationship between amines used for synthesis and the diastereomeric separation showed that amides made from chiral 1,2-amino alcohols gave superior separation to amides from chiral morpholines. The presence of a hydrogen bond donor on the amide side chain seems to be required for a better diastereomeric separation.     

X-ray crystallographic determination of the structure and conformation of trans-2-tribromomethyl-5-trichloromethyl-1,3-dioxolan-4-one: an analogue of chloralide

trans-2-Tribromomethyl-5-trichloromethyl-1,3-dioxolan-4-one is monoclinic,P2₁/c,a=6.381(6),b=17.116(6),c=10.598(5) Å,=94.07(6)°,Z=4. The structure was solved by direct methods from data collected at room temperature on an Enraf-Nonius CAD4 diffractometer, and refined by full-matrix least squares to a finalR value of 0.042 using 1274 reflections. The conformation of the molecule is very similar to that of chloralide with the 5-mem-bered ring being almost planar. Evidence is provided for a possible C-HO intermolecular interaction. The average C-Br distance is 1.931(11) Å and the average Br-C-Br angle is 109.7(9)°. A table of average C-Br bond lengths and Br-C-Br angles, with the ranges for these parameters, in compounds containing -CBr₃ groups is given. Some¹H NMR and mass spectra data are included for the title compound and for chloralide.     

C−H...π(Ar)...H−C host-guest interactions in a novel air-stable cyanoborate clathrate

The host compound forms a coordinato-clathrate in a coordination assisted host lattice. The host lattice is provided by hydrogen bonding between the nitrogen atom of the cyano group and two hydrogen atoms from the phosphonium methyl group. Guest molecules ofp-xylene occupy constricted channels in the lattice. The twop-xylene molecules participate in C–H...(Ar)...H–C interactions. Results from searches of the Cambridge Structural Database for other C–H...(Ar)...H–C and C–H...(Ar) interactions are presented.     

Two acetylamino derivatives of 2,4-bis(trichloromethyl)-1,3-benzdioxin showing different types of hydrogen bonding: (a) (C13C)CH⋯O=C and (b) N-H⋯O=C

8-Acetylamino-6-methyl-2,4-bis(trichloromethyl)-1,3-benzdioxin, (I), is monoclinic,P2₁/c,a=15.174(4),b=11.977(7),c=9.911(3)Å,=99.72(2)°. 6-Acetylamino-2,4-bis(trichloromethyl)-1,3-benzdioxin, (II), is monoclinic,P2₁/_n,a=5.927(4),b=40.623(1),c =7.120(3)Å,=91.39(4)°. In compound (I) the imino hydrogen atom is locked in an intramolecular hydrogen bond to the proximate oxygen atom of the heterocyclic ring and is not available for intermolecular hydrogen bonding. Instead the weakly acidic hydrogen atom [Cl₃C-C(2)]H takes part in a hydrogen bond to the carbonyl oxygen atom in another molecule. In compound (II) a normal intermolecular hydrogen bond of the type N-HO=C occurs. The 6-acetylam-ino group is twisted about the (C_Ar-N) bond such that the angles NHO=C, C_ArH_ArO=C, NHOH_ArC_Ar, at the carbonyl oxygen group total 360° (where NH is in the related molecule). The packing in both compounds takes the form of infinite chains and in compound (II) partial overlap of the aromatic ring and the acetylamino group, with very little offset, also occurs.     

Isomerism in some 1-oxa-3,5-dithians and the X-ray structure determination of 2,6-bis(trichloromethyl)-4-dichloromethylene-1-oxa-3,5-dithian

2,6-bis (trichloromethyl)-4-dichloromethylene-1-oxa-3,5-dithian is triclinic,P¯1,a=10.125(3),b=10.294(3),c=14.631(10) Å,=92.84(5),=96.51(5), =96.18(2)°,V=1503 ų,Z=4. The structure was solved by direct methods, from data collected at room temperature on an Enraf-Nonius CAD4 diffractometer, and refined by least squares to a finalR value of 0.035 using 3961 reflections. The conformation of the molecules is twist-boat, one molecule being almost symmetrically twisted about the O-C(Cl₂) direction. The range of endocyclic O-C-S angles is 111.8(3) to 115.1(3)° and data are given which support the possibility of there being a correlation between the endocyclic O-C(X)-S angle, the C-O-C(X)-C(Cl₃) torsion angle, and the C-S-C(X)-C(Cl₃) torsion angle. The -CCl₃ groups are in pseudoequatorial positions. Average bond lengths (Å) for the two molecules are C-O 1.405, C(sp ³)-S 1.822, C(sp ²)-S 1.759, C-C_eq 1.529 and average endocyclic angles (°) are O 117.3, C (sp ³) 113.5, S 97.4, C(sp ²) 119.3, the esds on the individual bond lengths and angles being in the ranges of 0.003–0.004 Å and 0.2–0.4° respectively.     

Structure and conformation of 6-nitro-2-trichloromethyl-1,3-benzdioxin-4-one: X-ray crystallographic determination

6-nitro-2-trichloromethyl-1,3-benzdioxin-4-one is monoclinic,P2₁/n;a=5.969(2),b=11.646(1),c=16.953(1) Å;=98.03(2)°;Z=4. The structure was solved by direct methods, from data collected at room temperature on an Enraf-Nonius CAD4 diffractometer, and refined by least squares to a finalR value of 0.030 using 1530 reflections.The heterocyclic ring is a distorted half-boat and is substituted equatorially by a trichloromethyl group. Dihedral angles are (a) 4.87(7)° between the mean plane of the aromatic ring and the plane containing the two carbon atoms common to both rings plus the two atoms bonded to these, and (b) 16.8(2)° between the carbonyl group and the aromatic ring. The conformation is discussed with reference to the two previously reported X-ray structures of 1,3-benzdioxin-4-ones and to two isocoumarins.