Derivatization of tributyltin with sodium tetrakis(4-fluorophenyl)-borate for sensitivity improvement of tandem mass spectrometry.

Derivatization of tributyltin for tandem mass spectrometry is described. Tributyltin (TBT) and triphenyltin (TPT) were derivatized with sodium tetrakis(4-fluorophenyl)borate. After optimization of their MS/MS conditions, derivatization conditions were examined. Under the optimum conditions using in-situ derivatization, the calibration curves for the TBT and TPT were linear in the ranges of 0.4 - 200 and 1.2 - 200 pg of Sn, respectively. The detection limits for TBT and TPT were 0.07 and 0.43 pg of Sn, respectively. In the case of TBT, the detection limit with 4-fluorophenylation was improved about five times compared with that with pentylation (0.35 pg). This improvement is ascribed to the bond-dissociation energy of Sn-aryl being stronger than that of Sn-alkyl. Namely, the selective fragmentation of 4-fluorophenyl TBT resulted in high sensitivity. The relative recoveries of TBT and TPT from seawater were 99 and 109%, respectively. The method was successfully applied to the seawater samples.     

Contribution of recoil implantation to removal of monolayer impurity atoms on metal surfaces

The decay of one monolayer gold atoms at the nickel surface by bombardment with 5 keV Ar⁺ ions at room temperature has been studied by means of the RBS technique. It is found that the gold concentration decreases bi-exponentially with increasing ion fluence. It is shown that the fast decay component gives the removal cross-section which is the summation of the desorption and the recoil-implantation cross-sections. The recoil-implantation cross-section is evaluated from the difference between the removal cross-section and the desorption cross-section obtained at a previous high-temperature experiment.     

Assignment of the 13C-NMR spectrum of phenanthro[4,3-A]dibenzothiophene through the utilization of two-dimensional relayed coherence transfer and double quantum coherence spectroscopy

Total assignment of the ¹³C-nmr spectrum of the helical molecule phenanthro[4,3-a]dibenzothiophene at 125.762 MHz is reported. Assignments were made by the combined application of ¹³C-¹³C autocorrelated double quantum coherence and heteronuclear relayed coherence transfer (RELAY) experiments.     

Dihydropyrene annelated with dihydrothieno[3.4-b]pyrazine: synthesis and photoswitching property

In this study, 9,10-diacetoxyl-2,7-di-tert-butyl-trans-10b,10c-dimethyl-10b,10c-dihydropyrene annelated with a dihydrothieno[3.4-b]pyrazine unit (1a) was prepared, for the first time, from 5,13-di-tert-butyl-8,16-dimethyl-1,2,9,10-tetrahydroxy[2.2]metacyclophane and 3,4-diaminothiophene in two steps. The photoisomerization property of 1 was investigated by UV and ¹H NMR spectroscopies, and the quantitative isomerization between the more stable dihydropyrene (DHP) form and the less stable metacyclophane-diene (MCPD) form was observed. A thermally induced return reaction from the MCPD to the DHP form was examined at various temperatures, and the reaction rate was 0.0049 min⁻¹ at 45 °C, which is slower than that of the parent MCPD.     

Computational simulations of HIV-1 proteases--multi-drug resistance due to nonactive site mutation L90M

Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the proteins that currently available anti-HIV-1 drugs target. Inhibitors of HIV-1 PR have become available, and they have lowered the rate of mortality from acquired immune deficiency syndrome (AIDS) in advanced countries. However, the rate of emergence of drug-resistant HIV-1 variants is quite high because of their short retroviral life cycle and their high mutation rate. Serious drug-resistant mutations against HIV-1 PR inhibitors (PIs) frequently appear at the active site of PR. Exceptionally, some other mutations such as L90M cause drug resistance, although these appear at nonactive sites. The mechanism of resistance due to nonactive site mutations is difficult to explain. In this study, we carried out computational simulations of L90M PR in complex with each of three kinds of inhibitors and one typical substrate, and we clarified the mechanism of resistance. The L90M mutation causes changes in interaction between the side chain atoms of the 90th residue and the main chain atoms of the 25th residue, and a slight dislocation of the 25th residue causes rotation of the side chain at the 84th residue. The rotation of the 84th residue leads to displacement of the inhibitor from the appropriate binding location, resulting in a collision with the flap or loop region. The difference in levels of resistance to the three inhibitors has been explained from energetic and structural viewpoints, which provides the suggestion for promising drugs keeping its efficacy even for the L90M mutant.     

Pd0‐Mediated Rapid Cross‐Coupling Reactions,the Rapid C‐[11C]Methylations,Revolutionarily Advancing the Syntheses of Short‐Lived PET Molecular Probes

Positron emission tomography is a noninvasive method for monitoring drug (or diagnostic) behavior and its localization on the target molecules in the living systems, including the human body, using a short‐lived positron‐emitting radionuclide. New methodologies for introducing representative short‐lived radionuclides, ¹¹C and ¹⁸F, into the carbon frameworks of biologically active organic compounds have been established by developing rapid C‐[¹¹C]methylations and C‐[¹⁸F]fluoromethylations using rapid Pd⁰‐mediated cross‐coupling reactions between [¹¹C]methyl iodide (sp³‐hybridized carbon) and an excess amount of organotributylstannane or organoboronic acid ester having sp²(phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp³(benzyl and cinnamyl)‐hybridized carbons; and [¹⁸F]fluoromethyl halide (iodide or bromide) and an organoboronic acid ester, respectively. These rapid reactions provide a firm foundation for an efficient and general synthesis of short‐lived ¹¹C‐ or ¹⁸F‐labeled PET molecular probes to promote in vivo molecular imaging studies.     

Thermosensitive Ion Channel Activation in Single Neuronal Cells by Using Surface‐Engineered Plasmonic Nanoparticles

Controlling cell functions using external photoresponsive nanomaterials has enormous potential for the development of cell‐engineering technologies and intractable disease therapies, but the former currently requires genetic modification of the target cells. We present a method using plasma‐membrane‐targeted gold nanorods (pm‐AuNRs) prepared with a cationic protein/lipid complex to activate a thermosensitive cation channel, TRPV1, in intact neuronal cells. Highly localized photothermal heat generation mediated by the pm‐AuNRs induced Ca²⁺ influx solely by TRPV1 activation. In contrast, the use of previously reported cationic AuNRs that are coated with a conventional synthetic polymer also led to photoinduced Ca²⁺ influx, but this influx resulted from membrane damage. Our method provides an optogenetic platform without the need for prior genetic engineering of the target cells and might be useful for novel TRPV1‐targeted phototherapeutic approaches.     

Reactions of acetonitrile coordinated to a nitrosylruthenium complex with H2O or CH(3)OH under mild conditions: structural characterization of imido-type complexes

The reaction of cis-[Ru(NO)(CH(3)CN)(bpy)(2)](3+) (bpy = 2,2'-bipyridine) in H(2)O at room temperature proceeded to afford two new nitrosylruthenium complexes. These complexes have been identified as nitrosylruthenium complexes containing the N-bound methylcarboxyimidato ligand, cis-[Ru(NO)(NH=C(O)CH(3))(bpy)(2)](2+), and methylcarboxyimido acid ligand, cis-[Ru(NO)(NH=C(OH)CH(3))(bpy)(2)](3+), formed by an electrophilic reaction at the nitrile carbon of the acetonitrile coordinated to the ruthenium ion. The X-ray structure analysis on a single crystal obtained from CH(3)CN-H(2)O solution of cis-[Ru(NO)(NH=C(O)CH(3))(bpy)(2)](PF(6))(3) has been performed: C(22)H(20.5)N(6)O(2)P(2.5)F(15)Ru, orthorhombic, Pccn, a = 15.966(1) A, b = 31.839(1) A, c = 11.707(1) A, V = 5950.8(4) A(3), and Z = 8. The structural results revealed that the single crystal consisted of 1:1 mixture of cis-[Ru(NO)(NH=C(O)CH(3))(bpy)(2)](2+) and cis-[Ru(NO)(NH=C(OH)CH(3))(bpy)(2)](3+) and the structural formula of this single crystal was thus [Ru(NO)(NH=C(OH(0.5))CH(3))(bpy)(2)](PF(6))(2.5). The reaction of cis-[Ru(NO)(CH(3)CN)(bpy)(2)](3+) in dry CH(3)OH-CH(3)CN at room temperature afforded a nitrosylruthenium complex containing the methyl methylcarboxyimidate ligand, cis-[Ru(NO)(NH=C(OCH(3))CH(3))(bpy)(2)](3+). The structure has been determined by X-ray structure analysis: C(25)H(29)N(8)O(18)Cl(3)Ru, monoclinic, P2(1)/c, a = 13.129(1) A, b = 17.053(1) A, c = 15.711(1) A, beta = 90.876(5) degrees, V = 3517.3(4) A(3), and Z = 4.     

Functional evaluation of iron oxypyriporphyrin in protein heme pocket

The iron complex of oxypyriporphyrin, a porphyrinoid containing a keto-substituted pyridine, was coupled with apomyoglobin. The reconstituted ferric myoglobin was found to be five-coordinate without iron-bound water molecules. The anionic ligands such as CN (-) and N 3 (-) bound the myoglobin with high affinities, while neutral imidazole did not. The IR observation indicated that the azide complex was pure high-spin, although the corresponding native protein was in the spin-state equilibrium. The reduced myoglobin was five-coordinate but exhibited no measurable affinity for O 2. The affinity for CO was lowered down to 1/2400 as compared with native myoglobin. These anomalies were ascribed to the deformation in the iron coordination core after the replacement of one of the four pyrroles with a larger pyridine ring. The ligand binding analyses for the ferric and ferrous myoglobin suggest that the proximal histidine pulls the iron atom from the deformed core to reduce the interaction between the iron and exogenous ligands. Similarity of the reconstituted myoglobin with guanylate cyclase, a NO-responsive signaling hemoprotein, was pointed out.