ChemInform Abstract: CONFORMATIONAL ANALYSIS. 32. CONFORMATIONAL ENERGIES OF METHYL SULFIDE, METHYL SULFOXIDE, AND METHYL SULFONE GROUPS

Rats, mice, and rhesus monkeys were subjected in subchronic exposures to the chemicals p-chlorophenyl methyl sulfide, p-chlorophenyl methyl sulfoxide, and p-chlorophenyl sulfone. Ninety-one-day toxicity studies were conducted by administering test chemicals to rodents at dietary concentrations of 750, 1500, and 3000 ppm. Clinical signs observed included transient central nervous system (CNS) depression, anorexia, and depressed weight gains. Minor alterations of hematologic and clinical chemistry parameters were also present. Gross and microscopic tissue findings in mice and rats included enlargement, necrotic and megalocytic changes of the liver. Damage to bronchiolar epithelium was observed in mice only at the highest exposure level. A 14-day gavage study in monkeys used daily dosages ranging from 2.5 to 80 mg/kg with an additional 15 days allotted for a recovery phase in one-half the test animals. Compound-related findings included lethality, CNS depression, and emesis. There were no significant compound-induced alterations in electrocardiographic or ophthalmic parameters. Serum blood urea nitrogen and serum glutamic pyruvic transaminase values were elevated in the highest dosage groups for the three test materials concomitant with increases in liver and kidney weights. Microscopic lesions included proliferative changes in lymph nodes, spleen, and bone marrow; hepatocellular vacuolization, degeneration, and necrosis; thyroid follicular cell hyperplasia; and degenerative lesions in gastric and intestinal epithelium. No-observable-effect levels (NOELs) were not established for any of the three test chemicals in the species tested.

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A Caveat Concerning the Use of the AM1 and PM3 Semiempirical Methods in Calculating Conformational Preferences in Acyclic Amines and Saturated Azaheterocycles

Australian Journal of Chemistry ◽

10.1071/ch9930547 ◽

1993 ◽

Vol 46 (4) ◽

pp. 547 ◽

Cited By ~ 6

Author(s):

MJ Shephard ◽

MN Paddonrow

Keyword(s):

Conformational Analysis ◽

Lone Pair ◽

Conformational Energy ◽

Semiempirical Methods ◽

Poor Agreement ◽

Isopropyl Group ◽

Butyl Group ◽

Conformational Preferences ◽

Nitrogen Lone Pair ◽

Conformational Energies

A theoretical investigation of the conformational analysis of several acyclic amines, N- alkylated saturated azaheterocycles and alkylcyclohexanes (alkyl = Me, Et, isopropyl, t-butyl) has been carried out by using the MNDO, AM1 and PM3 semiempirical methods. It is found that all three methods correctly predict, qualitatively, the conformational preferences in alkylcyclohexanes, although the PM3 method underestimates the conformational energy for the t-butyl group by as much as 13 kJ/mol. Both AM1 and PM3 overestimate the conformational energy of the nitrogen lone pair to the extent that it exceeds that of the isopropyl group and (in the case of PM3) the t-butyl group, thereby leading to erroneous predictions of favoured conformations in amines and azaheterocycles . Thus, axial N-alkylpiperidines are predicted to be more stable than the equatorial conformers. Thus, application of the AM1 and PM3 methods to the conformational analysis of molecules containing amine functionalities is not recommended. Although the MNDO method gives a qualitative account of the conformational analysis of such molecules, with the exception of hexahydropyridazines and hexahydropyrimidines, the resulting conformational energies and molecular geometries are in poor agreement with experimental data.

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p-Chlorophenyl Methyl Sulfide, p-Chlorophenyl Methyl Sulfoxide, and p-Chlorophenyl Methyl Sulfone. I. Acute Toxicity and Bacterial Mutagenicity Studies

Journal of the American College of Toxicology ◽

10.1177/109158189301200407 ◽

1993 ◽

Vol 12 (4) ◽

pp. 369-376 ◽

Cited By ~ 1

Author(s):

A. Philip Leber ◽

Jack C. Dacre ◽

Daryl C. Thake ◽

Dennis C. Mays

Keyword(s):

Acute Toxicity ◽

Skin Irritation ◽

Rocky Mountain ◽

Test Results ◽

Water Contaminants ◽

Methyl Sulfide ◽

Methyl Sulfoxide ◽

Central Nervous System Depression ◽

Bacterial Mutations ◽

Rocky Mountain Arsenal

An acute toxicity battery was performed on a series of three chemicals (p-chlorophenyl methyl sulfide, p-chloro-phenyl methyl sulfoxide, and p-chlorophenyl methyl sulfone) which have been identified as ground water contaminants at the U.S. Army's Rocky Mountain Arsenal near Denver. The results indicate that these materials exhibit oral LD50 values in the ranges of 400–620 mg/kg in rats and 330–880 mg/kg in mice. Following dermal exposures, only the sulfide induced death in rabbits. This agent and the sulfoxide induced central nervous system depression for a period of up to 7 days postapplication. Skin irritation potencies in rabbit tests were in the order of sulfoxide > sulfone >> sulfide, whereas ocular test results revealed irritation potencies to be sulfoxide > sulfide > sulfone. Results of guinea pig testing indicated a lack of sensitization potential for all compounds. None of the test materials induced bacterial mutations in Salmonella (five strains) assays that employed Arochlor 1254- and phenobarbital-induced S-9 rat liver activation systems. The most overt short-term effects following exposure to one or more of these agents are the ocular effects and the neurologic/lethal potentials following dermal or oral contact.

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Conformational Analysis of C60 Ball-and-Chain Molecules: a Molecular Orbital Study

Australian Journal of Chemistry ◽

10.1071/ch9960395 ◽

1996 ◽

Vol 49 (3) ◽

pp. 395 ◽

Cited By ~ 3

Author(s):

MJ Shephard ◽

MN Paddonrow

Keyword(s):

Conformational Analysis ◽

Computational Study ◽

Hydrocarbon Chain ◽

Am1 Method ◽

Methyl Groups ◽

Chain Molecules ◽

Molecular Orbital Study ◽

C 30 ◽

Bichromophoric Molecules ◽

Conformational Energies

A computational study of the conformational analysis of a series of C60 ball-and-chain bichromophoric molecules (1)-(6) has been carried out by means of the AM1 and HF/3-21G//AM1 theoretical methods. It is found that the AM1 method underestimates both the relative conformational energies and the magnitude of the energy barriers folded and extended conformers. In contrast, the HF/3-21G//AM1 method gives reasonable values for these quantities. The HF/3-21G//AM1 calculated energy differences between the folded and extended conformers of systems (2)-(5) are less than 5 kJ/mol and the barriers to their interconversion are c. 30 kJ/mol. The conformational bias in these systems may be modified by the judicious placement of methyl groups in the region of the hydrocarbon chain closest to the C60 cage. It is found that the length of the chain and the nature of the non-C60. chromophore have little effect on the conformational energetics.

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