Toluene, biological oxidation

Benzene oxide and compounds derived from it are carcinogenic and can react with DNA to induce mutations This difference m the site of biological oxidation—ring versus side chain—seems to be responsible for the fact that benzene is carcinogenic but toluene is not... 

Assumption of a similar metabolic change might clear up some aspects of the biological oxidation of toluene to benzoic acid. Bray, Thorpe and White131 have studied the kinetics of the oxidation of both benzyl alcohol and benzaldehyde to benzoic acid. The velocity constant for the oxidation of the alcohol is 1.0, and that for the aldehyde is only 0.3, indicating that both cannot be intermediates in the oxidation of toluene. Since the alcohol has already been shown to be an intermediate, it follows that the aldehyde is not. They pointed out that hydrate formation and D-glu-curonic conjugation may precede oxidation. 

Another interesting class of five-membered aromatic heterocycles has recently been published by Tron et al. [54]. These compounds have biological activity in the nM range. An example of the formation of these furazan (1,2,5-oxadiazole) derivatives is shown in Scheme 9. The diol 50 was oxidized to the diketone 51 using TEMPO and sodium hypochlorite. Transformation to the bisoxime 52 was performed in an excess of hydroxylamine hydrochloride and pyridine at high temperature for several days. Basic dehydration of 52 formed two products (53a and b). A Mitsunobu reaction was then employed using toluene as solvent to form compound 53b in 24% yield. 

Biological. Robertson et al. (1992) reported that toluene dioxygenases from Pseudomonas putida FI and Pseudomonas sp. Strain JS 150 oxidized the methyl group forming 2-nitrobenzyl alcohol. 

Adducts to hemoglobin are perhaps the most useful means of biological monitoring by adduct formation. Hemoglobin is, of course, present in blood, which is the most accurate type of sample for biological monitoring. Adducts to blood plasma albumin are also useful monitors and have been applied to the determination of exposure to toluene diisocyanate, benzo(a)pyrene, styrene, styrene oxide, and aflatoxin Bj. The DNA adduct of styrene oxide has been measured to indicate exposure to carcinogenic styrene oxide.12... 

The latter is almost certainly involved in an interesting thermal equilibrium (22), which has been observed in both pyridine and toluene solutions. When [Mn4L8] (L = 243) (Section 41.3.5.3.ii) was treated with py, purple crystals [MnlvL2py2] -2py (L = 242) were obtained. An X-ray analysis738 proved the Mnlv/catecholate formulation Mn—O = 1.854(2) and Mn—N = 2.018(3)A, and a spectrophotometric study of the equilibrium (22) showed that the Mnlv form prevails at low temperature in the solutions. There seems to be a real possibility that some such redox changes may offer an explanation of the role of Mn in biological photosynthetic water oxidation. 

The determination of urinary cresols, particularly o-cresol, has been proposed as a biological monitoring method for toluene, as a fraction of the inhaled vapor is oxidized at the aromatic ring with the production of cresols. 

Borovik and co-workers (29-31) developed porous organic materials for reversible binding of CO, O2, and NO by means of gas chemical coordination to the metal centers. For immobihzation of metal centers, templated copolymerization was employed (Fig. 7). Material 14, for example, contained immobilized four-coordinate Co(II) centers, and the cobalt concentration ranged from 180 to 230 mol g with an average pore diameter of 25 A (31). Polymer 14 bound NO in toluene solution and even on the air-solid interphase, but was relatively inert toward other biologically important gases O2, CO2, and CO. Nitric oxide could be slowly released from 14 under ambient conditions. For example, after 30 days 80% of NO was lost. Heating the sample accelerated the gas release. 

Exposure to styrene is the main occupational hygiene problem in reinforced plastics industry, where it is used as a crosslinking agent and solvent in unsaturated polyester resins. In addition, workers are exposed to acetone which is used as a clean-up solvent. Other solvents, such as methylene chloride, toluene, xylene, heptane (TLV 400 ppm, the Finnish OEL 300 ppm), methylcyclohexane (TLV and the Finnish OEL 400 ppm), and butyl acetate (TLV and the Finnish OEL 150 ppm) may also be used. Styrene is neurotoxic. Styrene is also a suspected carcinogen because it is metabolized via styrene-7,8-oxide. The TLV and the Finnish OEL of styrene is 20 ppm. Urinary mandelic acid concentration is the most common biological monitoring method for styrene. The ACGIH BEI is 800 mg/g creatinine and the FIOH BEI 3.2 mmol/1. 

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