Ultrafast excited-state dynamics in vitamin B12 and related cob(III)alamins.

Femtosecond transient IR and visible absorption spectroscopies have been employed to investigate the excited-state photophysics of vitamin B12 (cyanocobalamin, CNCbl) and the related cob(III)alamins, azidocobalamin (N3Cbl), and aquocobalamin (H2OCbl). Excitation of CNCbl, H2OCbl, or N3Cbl results in rapid formation of a short-lived excited state followed by ground-state recovery on time scales ranging from a few picoseconds to a few tens of picoseconds. The lifetime of the intermediate state is influenced by the sigma-donating ability of the axial ligand, decreasing in the order CNCbl > N3Cbl > H2OCbl, and by the polarity of the solvent, decreasing with increasing solvent polarity. The peak of the excited-state visible absorption spectrum is shifted to ca. 490 nm, and the shape of the spectrum is characteristic of weak axial ligands, similar to those observed for cob(II)alamin, base-off cobalamins, or cobinamides. Transient IR spectra of the upper CN and N3 ligands are red-shifted 20-30 cm(-1) from the ground-state frequencies, consistent with a weakened Co-upper ligand bond. These results suggest that the transient intermediate state can be attributed to a corrin ring pi to Co 3d(z2) ligand to metal charge transfer (LMCT) state. In this state bonds between the cobalt and the axial ligands are weakened and lengthened with respect to the corresponding ground states.

Determination of 14 polycyclic aromatic hydrocarbons in mainstream smoke from domestic cigarettes.

Polycyclic aromatic hydrocarbons (PAHs) are a class of environmental pollutants created primarily from incomplete combustion of various organic materials including tobacco. Cigarette smoke is a complex mixture of various classes of compounds, including numerous PAHs, in both the mainstream and the sidestream smoke fractions. We measured the levels of 14 PAHs in mainstream smoke from unfiltered custom cigarettes made from individual tobacco types and 30 brands of domestic blended cigarettes using standardized smoking conditions, extraction from the Cambridge filter pads, and gas chromatography/mass spectrometry. Differences in smoke PAHs from cigarettes with selected tobacco blends were identified and illustrate how blend composition contributes to the overall mainstream smoke PAH profile. The PAH levels varied among the different commercial cigarette brands, with the amount of total mainstream smoke PAHs ranging from 1 to 1.6 microg per cigarette. Under machine smoking conditions, the mainstream smoke from domestic cigarettes had individual PAHs ranging from benzo[k]fluoranthene at levels below 10 ng/cigarette to naphthalene at levels of around 500 ng/cigarette. Low delivery cigarettes smoked with blocked filter vent holes dramatically increased the mainstream smoke PAH deliveries with respect to their unblocked counterparts. Inhalation of PAHs and other harmful chemicals from cigarette smoke are unique as they represent a routine voluntary exposure to common environmental pollutants.

Solid-phase microextraction-based approach to determine free-base nicotine in trapped mainstream cigarette smoke total particulate matter.

Characterizing nicotine delivery from tobacco products is important in the understanding of their addictive potential. Most previous studies report total nicotine and have not differentiated between nicotine in its protonated or free-base form. Rather than simply determining total nicotine, the method described in this paper determines the amount of free-base nicotine associated with trapped mainstream smoke particulate matter generated using a standardized smoking machine protocol. This method quantitatively determines volatile free-base nicotine associated with the particulate phase portion of mainstream cigarette smoke using solid-phase microextraction combined with gas chromatography-mass spectrometry. The headspace above total particulate matter from mainstream cigarette smoke trapped on a Cambridge filter pad (CFP) was analyzed for free-base nicotine in 26 cigarette brands. The selected cigarette brands were chosen to cover a wide range of tar and nicotine deliveries as measured under Federal Trade Commission machine smoking conditions. In the CFP's headspace the free-base nicotine levels ranged from 0.01 to 0.08 mg/cigarette. The measured ranges of free-base nicotine were remarkably similar over the different tar and nicotine delivery categories of full-flavored, light, and ultralight cigarette brands.

Inactivation of human immunodeficiency virus type 1 by porphyrins.

We have evaluated the anti-human immunodeficiency virus (HIV) activity of a series of natural and synthetic porphyrins to identify compounds that could potentially be used as microbicides to provide a defense against infection by sexually transmitted virus. For assays we used an epithelial HeLa-CD4 cell line with an integrated long terminal repeat-beta-galactosidase gene. For structure-activity analysis, we divided the porphyrins tested into three classes: (i) natural porphyrins, (ii) metallo-tetraphenylporphyrin tetrasulfonate (metallo-TPPS4) derivatives, and (iii) sulfonated tetra-arylporphyrin derivatives. None of the natural porphyrins studied reduced infection by more than 80% at a concentration of 5 micro g/ml in these assays. Some metal chelates of TPPS4 were more active, and a number of sulfonated tetra-aryl derivatives showed significantly higher activity. Some of the most active compounds were the sulfonated tetranaphthyl porphyrin (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced infection by 99, 96, 94, and 96%, respectively. Our observations indicate that at least some of these compounds are virucidal, i.e., that they render the virus noninfectious. The active compounds were found to inhibit binding of the HIV type 1 gp120 to CD4 and also to completely inhibit the ability of Env proteins expressed from recombinant vectors to induce cell fusion with receptor-bearing target cells. These results support the conclusion that modified porphyrins exhibit substantial activity against HIV and that their target is the HIV Env protein.