Divalent carbon(0) chemistry, part 2: Protonation and complexes with main group and transition metal Lewis acids.

Quantum-chemical calculations with DFT (BP86) and ab initio methods (MP2, SCS-MP2) were carried out for protonated and diprotonated compounds N-H(+) and N-(H(+))(2) and for the complexes N-BH(3), N-(BH(3))(2), N-CO(2), N-(CO(2))(2), N-W(CO)(5), N-Ni(CO)(3) and N-Ni(CO)(2) where N=C(PH(3))(2) (1), C(PMe(3))(2) (2), C(PPh(3))(2) (3), C(PPh(3))(CO) (4), C(CO)(2) (5), C(NHC(H))(2) (6), C(NHC(Me))(2) (7) (Me(2)N)(2)C==C==C(NMe(2))(2) (8) and NHC (9) (NHC(H)=N-heterocyclic carbene, NHC(Me)=N-substituted N-heterocyclic carbene). Compounds 1-4 and 6-9 are very strong electron donors, and this is manifested in calculated protonation energies that reach values of up to 300 kcal mol(-1) for 7 and in very high bond strengths of the donor-acceptor complexes. The electronic structure of the compounds was analyzed with charge- and energy-partitioning methods. The calculations show that the experimentally known compounds 2-5 and 8 chemically behave like molecules L(2)C which have two L-->C donor-acceptor bonds and a carbon atom with two electron lone pairs. The behavior is not directly obvious when the linear structures of carbon suboxide and tetraaminoallenes are considered. They only come to the fore on reaction with strong electron-pair acceptors. The calculations predict that single and double protonation of 5 and 8 take place at the central carbon atom, where the negative charge increases upon subsequent protonation. The hitherto experimentally unknown carbodicarbenes 6 and 7 are predicted to be even stronger Lewis bases than the carbodiphosphoranes 1-3.     

Electrophoresis of soft particles at high electrolyte concentrations: an interpretation by the Henry theory

The existence of electrophoretic mobility at high electrolyte concentrations defines a remarkable peculiarity in the electrosurface characteristics of soft particles. According to Ohshima [H. Ohshima, Colloids Surf. 103 (1995) 249], this effect is caused by the electroosmotic flow within the soft particle shell. An explanation supporting Ohshima's conclusion can be derived from classic electrokinetic theories. Based on the Henry theory [D.C. Henry, Proc. R. Soc. London Ser. A 133 (1931) 106], we demonstrate that the electrophoretic mobility of soft particles does not disappear at decinormal concentration.     

Thiyl radical interaction with pyrimidine C5-C6 double bond

Addition and elimination interaction of thiyl radicals with the C5-C6 double bond in pyrimidines was studied by the pulse radiolysis technique in aqueous solution with the use of different monitoring systems. For this purpose, p-thiocresol, cysteamine hydrochloride, and mercaptoethanol were used. The rate constants of addition and elimination of thiyl radicals were determined by applying the modified version of ACUCHEM (computer program for modeling complex reaction systems). Aliphatic thiyl radicals add to the pyrimidine C5-C6 double bond with k = 1.0-3.0 x 10(7) dm3 mol(-1) s(-1), whereas elimination takes place with k = 0.7-2.0 x 10(5) s(-1). Quantum chemical calculations at the B3LYP/6-31G(d)/PCM level show that the addition should occur at the C6 position of the pyrimidine ring and that the energy of interaction between thiyl radicals and the pyrimidine double bond C5-C6 is low.     

Ionization of cyclic aromatic amines by free electron transfer: products are governed by molecule flexibility

The bimolecular electron transfer from secondary aromatic amines to parent radical cations of nonpolar solvents such as alkanes and alkyl chlorides results in the synchronous formation of amine radical cations as well as aminyl radicals, in comparable amounts. If as for cyclic aromatic amines (c-Ar(2)NH) the intramolecular bending motion around the amine group is restricted in varying degrees (acridane, phenothiazine) or completely prevented (carbazole), then this picture is modified. In the free electron transfer, the completely rigid carbazole yields exclusively amine radical cations. Acridane exhibits preferred radical cations, but phenothiazine with the more flexible six-membered ring involving sulfur as a further heteroatom follows the common two-product rule; see above. The phenomenon is reasoned by a peculiarity in the bimolecular free electron transfer where after diffusional approach the actual electron jump proceeds in the ultrashort time range. Therefore, it reflects femtosecond molecular motions which, in the case of free mobility, continuously pass through different molecule conformers, combined with fluctuation of the electrons of the responsible molecular n-orbitals. The rigid systems, however, do not show this effect because of a nonexistent bending motion.     

A matrix isolation study of the C(s) symmetric OCNO(X 2A') radical

Here we report the first experimental detection of the C(s) symmetric nitroformyl radical, OCNO(X 2A') in a nitrogen-carbon dioxide matrix at 10 K using a Fourier transform infrared spectrometer (FTIR). The nu1 vibrational frequency was observed at 2113 cm(-1). This assignment was confirmed by follow-up experiments using isotopically labeled reactant molecules (15N, 18O, 13C). To synthesize this radical, we irradiated solid nitrogen-carbon dioxide ice mixtures with energetic electrons at 10 K. Suprathermal nitrogen atoms in their electronic ground and/or first electronically excited state were generated via the radiation induced degradation of molecular nitrogen; these atoms could then react with carbon dioxide to eventually yield the nitroformyl radical. We also investigated the kinetics of the formation of the nitroformyl radical and support the arguments with computations on the doublet and quartet OCNO potential energy surfaces (PESs).     

Lewis Acid Catalyzed Condensation–Cyclization Cascade: Direct Synthesis of Di/Trifluoromethyl‐1,2,3,4‐tetrahydroquinazolines

Condensed heterocycles such as quinazolines constitute the framework of many promising drugs. The great impact of the dramatic fluorine effect in pharmaceuticals prompted a great surge in the quest for fluorinated drug design resulting in over 20 % fluorine‐containing drugs in the market today. Therefore, finding an efficient and cost‐effective method for the direct synthesis of fluorine‐tagged quinazoline systems is of great significance in the pharmaceutical arena. For the first time, a one‐pot sequential condensation–cyclization reaction to form selectively the difluoro/trifluoromethylated tetrahydroquinazolines from simple components difluoro/trifluoroacetaldehyde hemiacetal and aromatic amines is reported. Our recent studies using difluoro/trifluoroacetaldehyde hemiacetal as simple and elegant difluoro/trifluoromethyl synthons and metal triflates such as gallium triflate as safe and stable Lewis acid catalysts led us to this direct synthesis protocol for the expedient and convenient synthesis of fluorinated quinazolines. DFT calculations at PCM/B3LYP/6‐31++G** were carried out for evaluating a possible reaction mechanism for this cyclization. According to the DFT calculations, product stereochemistry is thermodynamically driven, favoring the cis isomer as the major product, which is also confirmed experimentally.     

Two-dimensional electrophoresis of membrane proteins

One third of all genes of various organisms encode membrane proteins, emphasizing their crucial cellular role. However, due to their high hydrophobicity, membrane proteins demonstrate low solubility and a high tendency for aggregation. Indeed, conventional two-dimensional gel electrophoresis (2-DE), a powerful electrophoretic method for the separation of complex protein samples that applies isoelectric focusing (IEF) in the first dimension and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in the second dimension, has a strong bias against membrane proteins. This review describes two-dimensional electrophoretic techniques that can be used to separate membrane proteins. Alternative methods for performing conventional 2-DE are highlighted; these involve replacing the IEF with electrophoresis using cationic detergents, namely 16-benzyldimethyl-n-hexadecylammonium chloride (16-BAC) and cetyl trimethyl ammonium bromide (CTAB), or the anionic detergent SDS. Finally, the separation of native membrane protein complexes through the application of blue and clear native gel electrophoresis (BN/CN-PAGE) is reviewed, as well as the free-flow electrophoresis (FFE) of membranes.     

Transesterification and amide cis-trans isomerization in Zn and Cd complexes of the chelating amino acid ligand Boc-Asp(Dpa)-OBzl

The amino acid derivative Boc-Asp-OBzl (Boc=N-butyloxycarbonyl; Asp=aspartic acid; Bzl=benzyl) was functionalized by coupling its carboxylate side chain to dipicolylamine. This yielded the tridentate nitrogen donor ligand Boc-Asp(Dpa)-OBzl (-OBzl). The compound -OBzl contains three different carbonyl groups: a tertiary amide linkage between Asp and Dpa, a C-terminal benzyl ester function, and an N-terminal urethane protecting group. NMR spectra were used to compare the reactivity of these moieties. The Boc protecting group gives rise to two isomers, (E, 9%) and (Z, 91%). Coordination of Cd(NO3)2 and Zn(NO3)2 yielded the complexes and. These compounds have significantly reduced barriers to rotation about the tertiary amide C-N bond compared with the free ligand (-OBzl:18.5 kcal mol-1 in CDBr3;: 12.9 kcal mol-1 in (CD3)2CO;: 13.8 kcal mol-1 in (CD3)2CO). Both complexes readily undergo transesterification in methanol or CD3OD. Experimental pseudo-first order rate constants were determined in CD3OD and (CD3)2CO:CD3OD (3:1;). It was found that the zinc complex (k=(2.28+/-0.02)x10(-4) s-1) is significantly more reactive than the cadmium complex (k=(1.41+/-0.03)x10(-6) s-1). In order to study their tertiary amide cis-trans isomerization, the cadmium complex [(-OCH3)Cd(NO3)2] was synthesized, and the zinc complex [(-OCD3)Zn(NO3)2] was generated in situ in (CD3)2CO:CD3OD (3:1). The barriers to rotation were determined (:14.1 kcal mol-1 in CD3OD;: 13.4 kcal mol-1 in (CD3)2CO:CD3OD (3:1)). Our results show that the stronger Lewis-acid zinc(II) is significantly more active than cadmium(II) in the acceleration of the transesterification. This is in marked contrast to the tertiary amide bond rotation which is comparably fast with both metal ions.     

Investigation,by single photon ionisation (SPI)–time-of-flight mass spectrometry (TOFMS), of the effect of different cigarette-lighting devices on the chemical composition of the first cigarette puff

Soft single-photon ionisation (SPI)–time-of-flight mass spectrometry (TOFMS) has been used to investigate the effect of different cigarette-lighting devices on the chemical composition of the mainstream smoke from the first cigarette puff. Lighting devices examined were a Borgwaldt electric lighter, a propane/butane gas lighter, a match, a candle, and the burning zone of another cigarette. To eliminate the effects of the different masses of tobacco burnt by use of the different lighting methods a normalisation procedure was performed which enabled investigation of changes in the chemical patterns of the resulting smoke. When another cigarette was used as the lighting device, elevated levels of ammonia and other nitrogen-containing substances were observed. These are high in the sidestream smoke of the cigarette used for lighting and would be drawn into the mainstream smoke of the cigarette being lit. In contrast, smoke from the cigarette lit by the electric lighter contained slightly higher normalised amounts of isoprene. Lighting the cigarette by use of a candle resulted in larger amounts of substances, e.g. benzene, which most probably originated from thermal decomposition of wax. The composition of the first puff of smoke obtained by use of the three lighting methods with open flames (gas lighter, match, and candle) was usually similar whereas the composition of the smoke produced by use of the electric lighter and the cigarette as the lighter were more unique. The chemical patterns generated by the different lighting devices could, however, be separated by principal-component analyses. Two additional test series were also studied. In the first the cigarette was lit with an electric lighter, then extinguished, the ash was cut off, and the cigarette was re-lit. In the second the cigarette was heated in an oven to 80 °C for 5 min before being lit. These treatments did not result in changes in the chemical composition compared with cigarettes lit in the ordinary way. Figure Time-of-flight mass spectrometry (TOFMS) has been used to investigate the effect of different cigarette-lighting devices on the chemical composition of the mainstream smoke from the first cigarette puff