Au21 cage structures and their magic number tri-cations

We examine the stability and properties of three Au₂₁ cage structures, one with D₃ symmetry and denoted as Au₂₁ (D₃), which is novel, and the other two with C_2v symmetry. One, denoted as Au₂₁ (C_2v-1), has been previously reported but the other, denoted as Au₂₁ (C_2v-2), is novel. As reference Au₂₁ structures, we also examine a sheet isomer and a compact isomer, Au₂₁ (C_s-Tetra), formed by adsorbing an Au atom on Au₂₀ (T_d). For all structures, we consider charge ranging from −1 to +4. For the Au₂₁ cage structures, a primary property of interest is their spherical aromaticity, as measured by their nucleus independent chemical shift. Our focus is on charge +3 since each gold atom is assumed to contribute one (6s) valence electron, and 18 is a magic number for shell closing. We find that, although Au₂₁ (D₃)⁺³ has the largest aromaticity, it is not the most stable cage species. Surprisingly, Au₂₁ (C_2v-2), which is not even stable as a neutral cage species, is the most stable tri-cation cage species. We also examine the stability of (neutral) Au₂₁X_n cage structures relative to Au₂₁X_n structures derived from Au₂₁ (C_s-Tetra) (with X = F, Cl, Br, I and n = 1, 3, 5). We find that, although Au₂₁F₃ derived from Au₂₁ (D₃) has the largest aromaticity, it is not the most stable Au₂₁F₃ cage structure. Nonetheless, all cage structures are stabilized relative to Au₂₁ (C_s-Tetra) and, remarkably, for the trichlorinated, tribrominated, and triiodineated clusters, at least one cage structure is more stable than its Au₂₁ (C_s-Tetra) counterpart.     

Macrocyclic anion receptors based on directed hydrogen bonding interactions

Natural anion receptors use charge-neutral dipoles to bind small anions with high affinities and selectivities. A convergent and rigid display of hydrogen bond donors such as amide, thiourea and urea functional groups in macrocyclic scaffolds would be one of the most efficient ways to create synthetic anion receptors that mimic natural ones. In this article, we present examples of natural anion receptors and discuss the synthesis of neutral macrocyclic receptors and their anion binding properties.     

Avidin self-associates with boric acid gel suspensions: an affinity boron carrier that might be developed for boron neutron-capture therapy

It has been shown in preliminary studies that the antibacterial protein avidin self-associates with the boric acid gel polymer, and avidin-coated gel particles in the micrometer and submicrometer size ranges are of interest for boron neutron-capture therapy (BNCT), which is neutron-induced fission of boron-10 to produce intense alpha radiation for tumor destruction. The gel particles carry large amounts of boron-10 and are theoretically able effect a meaningful tissue dosing through BNCT. A gross precipitation of gel particles occurs within 46 min of mixing when the avidin/colloid ratio is about 0.34 g avidin/g colloid. This is a minimum time if gel and avidin concentrations are in the low microgram/milliliter range, but at higher proportions of avidin the time delay to precipitation increases significantly; i.e., the colloid surface becomes blocked, inhibiting lattice formation. The avidin-coated gel particles eventually cross-link, forming a solid matrix and precipitating on a timescale measured on the order of an hour. At shorter exposure times rapid agglutination-like reactions were observed with biotinylated bovine albumin, suggesting that two-stage pretargeting of specific tissues should be possible with biotinylated antitumor antibodies. However, for BNCT to be practical, avidin's interaction with the gel needs to be strengthened, and all aryl-B(OH)(2) groups on the particle surfaces must be blocked, or else the particles will interact strongly and nonspecifically with each other and with the carbohydrate groups present on most cell surfaces. Glyceric acid delays the precipitation of the particle suspensions while most simple and complex carbohydrates accelerate it.     

The solid state structure of [b(10)h(11)](-) and its dynamic NMR spectra in solution

The structure of [PPh(3)(benzyl)][B(10)H(11)] was determined at -123 degrees C and 24 degrees C by single-crystal X-ray analyses. The B(10) core of [B(10)H(11)](-) is similar in shape to that of [B(10)H(10)](2)(-). The 11th H atom asymmetrically caps a polar face of the cluster and shows no tendency for disorder in the solid state. Variable temperature multinuclear NMR studies shed light on the dynamic nature of [B(10)H(11)](-) in solution. In addition to the fluxionality of the cluster H atoms, the boron cage is fluxional at moderate temperatures, in contrast to [B(10)H(10)](2)(-). Multiple exchange processes are believed to take place as a function of temperature. Results of ab initio calculations are presented. Crystal data: [PPh(3)(benzyl)][B(10)H(11)] at -123 degrees C, P2(1)/c, a = 9.988(2) A, b = 18.860(2) A, c = 15.072(2) A, beta = 107.916(8) degrees, V = 2701.5(7) A(3), Z = 4; [PPh(3)(benzyl)][B(10)H(11)] at 24 degrees C, P2(1)/c, a = 10.067(5) A, b = 19.009(9) A, c = 15.247(7) A, beta = 107.952(9) degrees, V = 2775(2) A(3), Z = 4.     

Complexes derived from 4-amino-3-methyl-5-thione-1,2,4-triazole and monoorganomercury moieties. Crystal structure of (4-amino-5-mercapto-3-methyl-1,2,4-triazolato)methylmercury(II)

The compounds [HgR(L)] (R = Me or Ph; L = 4-amino-5-mercapto-3-methyl-1,2,4-triazolate) have been prepared and the crystal structure of the methylmercury(II) compound determined. This compound crystallizes in the monoclinic space group P21/n with a = 5.087(1), b = 10.102(1), c = 16.167(2) Å, β = 98.56(1)°, Z = 4 (R = 0.027; R_w = 0.030). It is formed of molecules in which the triazolate anion is bound to mercury strongly via the S atom and weakly via the amine N; there is also a weak intermolecular interaction between the endocyclic N and the Hg atom of a neighbouring unit.     

Catalyzed hydroboration of allyl sulfonamides

The hydroboration of allyl sulfonamides (4-H₃CC₆H₄SO₂NRCH₂CH=CH₂: R=H, 1; Ph, 2; Bz, 3) with catecholborane (HBcat) using different rhodium catalysts has been examined using multinuclear NMR spectroscopy. Reactions give complex product distributions, regardless of the choice of catalyst, arising from a competing isomerization reaction. This isomerization reaction can be used with N-substituted allyl sulfonamides 2 and 3 to give the corresponding enamines (4-H₃CC₆H₄SO₂CH=CH₂CH₃), which in turn react with HBcat to give regioselective formation of one isomer (4-H₃CC₆H₄SO₂NRCH₂CH₂(Bcat)CH₃).     

Ultra-sensitive Mass Spectrometric and Other Advanced Methods Applied to Biological Samples; Second interlaboratory comparison study for the analysis of 239Pu in synthetic urine at the µBq (~100 aCi) level by mass spectrometry

Summary As a follow up to the initial 1998 intercomparison study, a second study was initiated in 2001 as part of the ongoing evaluation of the capabilities of various ultra-sensitive methods to analyze ²³⁹Pu in urine samples. The initial study¹ was sponsored by the Department of Energy, Office of International Health Programs to evaluate and validate new technologies that may supersede the existing fission tract analysis (FTA) method for the analysis of ²³⁹Pu in urine at the µBq/l level. The ultra-sensitive techniques evaluated in the second study included accelerator mass spectrometry (AMS) by LLNL, thermal ionization mass spectrometry (TIMS) by LANL and FTA by the University of Utah. Only the results for the mass spectrometric methods will be presented. For the second study, the testing levels were approximately 4, 9, 29 and 56 µBq of ²³⁹Pu per liter of synthetic urine. Each test sample also contained ²⁴⁰Pu at a ²⁴⁰Pu/²³⁹Pu atom ratio of ~0.15 and natural uranium at a concentration of 50 µBq/ml. From the results of the two studies, it can be inferred that the best performance at the µBq level is more laboratory specific than method specific. The second study demonstrated that LANL-TIMS and LLNL-AMS had essentially the same quantification level for both isotopes. Study results for bias and precision and acceptable performance compared to ANSI N13.30 and ANSI N42.22 have been compiled.     

Liquid chromatographic determination of pinacidil, a new antihypertensive drug, and its major metabolite, pinacidil N-oxide, in plasma

Two procedures are described, one for the determination of pinacidil, the other for the determination of both pinacidil and its metabolite, pinacidil N-oxide, in plasma. When only parent drug levels are required, the plasma proteins are precipitated with acetonitrile, the solids discarded and the supernatant is evaporated to dryness. The residue is then reconstituted for analysis. For the determination of both drug and metabolite, the analytes are selectively retained from plasma on a solid-phase extraction column and eluted with methanol. After evaporation to dryness, the residue is reconstituted in mobile phase. Both procedures utilize reversed-phase liquid chromatographic separations with ultraviolet detection. The limits of detection are 10 ng/ml pinacidil in plasma and 5 ng/ml each of pinacidil and pinacidil N-oxide in plasma for the two procedures, respectively.     

Protein farnesyltransferase: Flexible docking studies on inhibitors using computational modeling

Summary Using MacroModel, peptide, peptidomimetic and non-peptidomimetic inhibitors of the zinc metalloenzyme, farnesyltransferase (FTase), were docked into the enzyme binding site. Inhibitor flexibility, farnesyl pyrophosphate substrate flexibility, and partial protein flexibility were taken into account in these docking studies. In addition to CVFM and CVIM, as well as our own inhibitors FTI-276 and FTI-2148, we have docked other farnesyltransferase inhibitors (FTIs) including Zarnestra, which presently is in advanced clinical trials. The AMBER* force field was employed, augmented with parameters that were derived for zinc. A single binding site model that was derived from the crystal structure of CVFM complexed with farnesyltransferase and farnesylpyrophosphate was used for these studies. The docking results using the lowest energy structure from the simulation, or one of the lowest energy structures, were generally in excellent agreement with the X-ray structures. One of the most important findings of this study is that numerous alternative conformations for the methionine side chain can be accommodated by the enzyme suggesting that the methionine pocket can tolerate groups larger than methionine at the C-terminus of the tetrapeptide and suggesting alternative locations for the placement of side chains that may improve potency.