Influence Of Alkyl Substitution Research Articles

The influence of alkyl substitution on the in vitro metabolism and mutagenicity of benzo[a]pyrene

In recent years concerns over consumer exposure to mineral oil aromatic hydrocarbons (MOAH), especially those containing alkylated polycyclic aromatic hydrocarbons (PAHs), have emerged. This is especially due to the fact that some PAHs are known to be genotoxic and carcinogenic upon metabolic activation. However, available toxicological data on PAHs mainly relate to non-substituted PAHs with limited data on alkyl substituted PAHs. Therefore, the aim of the present study was to characterize in more detail the effect of alkyl substitution on the metabolism and mutagenicity of benzo[a]pyrene (B[a]P), a PAH known to be genotoxic and carcinogenic. To this end, the oxidative metabolism and mutagenicity of B[a]P and a series of its alkyl substituted analogues were quantified using in vitro microsomal incubations and the Ames test. The results obtained reveal that upon alkylation the metabolic oxidation shifts to the aliphatic side chain at the expense of aromatic ring oxidation. The overall metabolism, including metabolism via aromatic ring oxidation resulting potentially in bioactivation, was substantially reduced with elongation of the alkyl side chain, with metabolism of B[a]P with an alkyl substituent of >6 C atoms being seriously hampered. In the Ames test upon metabolic activation, the methyl substitution of B[a]P resulted in an increase or decrease of the mutagenic potency depending on the substitution position. The relevant pathways for mutagenicity of the selected monomethyl substituted B[a]P may involve the formation of a 7,8-dihydrodiol-9,10-epoxide, a 4,5-oxide and/or a benzylic alcohol as an oxidative side chain metabolite which subsequently may give rise to an unstable and reactive sulfate ester conjugate. It is concluded that alkylation of B[a]P does not systematically reduce its mutagenicity in spite of the metabolic shift from aromatic to side chain oxidation.

Influence of alkyl substitution on the supramolecular organization of thiophene- and dioxine-based oligomers

The influence of the position and geometry of alkyl substituents on the supramolecular organization of thiophene- and dioxine-based oligomers is investigated.

Reactions of manganese(III) and copper(II) complexes with 3,7,12,18-tetramethyl-2,8,13,17-tetrabutylporphine in AcOH-H2SO4 mixed solvents

The forms of existence and reactions of manganese(III) and copper(II) complexes with 3,7,12,18-tetramethyl-2,8,13,17-tetrabutylporphine in H2SO4, AcOH, and their mixtures of variable composition were studied. The quantitative characteristics of reversible single-electron oxidation and dissociation for the Mn(III) and Cu(II) complexes, respectively, were obtained. The formation constant of the oxidized metal porphyrin was determined for the first time. The copper(II) complex was used to devise the first kinetic scheme described satisfactorily by two kinetic equations interpreted in terms of a single mechanism of dissociation of metal porphyrins in AcOH-H2SO4 mixtures by means of two methods of accounting the equilibrium of acid dissociation of H2SO4 in acetic acid. The mechanism of the influence of alkyl substitution on the electronic structure of the coordination site in the complexes is explained.

The influence of alkyl substitution in acids on their performance in the buccal absorption test.

Abstract A method to determine the passage of acids into the buccal membrane of man is presented. The absorption is shown to be the passive entry into a lipid phase. There is an increase in absorption of the acids due to alterations in partition characteristics with increasing chain length of n-fatty acids from butyric to dodecanoic. Methyl substitution of benzoic acid increases the absorption with mono- and di-substituents, but decreases the absorption with the tri- and tetra-substituents by lowering the pKa. Predictions of the relative absorption and excretion in man of these acids is included.

Quantum-chemical study of radical reactions in polymer systems II. Study of mechanism of regeneration of nitroxyl radicals from HALS inhibitors by acylperoxyl radical attack—comparison with peroxyl radicals

The mechanism of regeneration of >NO radicals from O-methylsubstituted hydroxylamine by attack of acylperoxyl radicals was studied by the AM1 quantum-chemical method. The reaction path studied has a remarkably lower barrier (by 36 kJ/mol) than the reaction path in case of the peroxyl radical. Thus acylperoxyl radicals can play an important role in the regeneration mechanism, but not before the late stages of oxidation, where their increased concentration can be expected. The influence of alkyl substitution (on the nitrogen atom of the nitroxyl group) on the reaction barrier was also studied. It was found that substitution increases the barrier from 34 to 50 kJ/mol, while the steric influence of tetramethyl substitution (in 2,2,6,6-tetramethylpiperidinyl oxide) on this barrier is negligible.

Substituent effect on the stereochemistry of H2-receptor antagonists of the phenylformamidine series. A conformation-dependent mode of interaction with the H2 receptor

The influence of alkyl substitution on the stereoisomerism of the formamidine cation (E,E vs E,Z) of several N-substituted (imidazolylphenyl)formamidines (1-10) was investigated. As (imidazolylphenyl)formamidines having alkyl substituents of more than three carbon atoms bind to H2-receptor preparations in a pseudoirreversible mode causing unsurmountable antagonism, the four isomeric butylformamidines (5-7 and 9) having comparable lipophilic character but different E,E/E,Z composition were investigated in H2-receptor assays to determine quantitatively any difference in their pseudoirreversible inhibitory pattern. It was found that the geometry of the formamidine cation is affected by the steric bulk of the substituent on the formamidine nitrogen. A relationship between the percentage of the E,E conformation of the formamidine cation and degree of pseudoirreversible antagonism was also found. The present studies support the hypothesis that bidentate hydrogen bonding plays an important role in the interaction of (imidazolylphenyl)formamidines with the H2 receptor.

Theoretical spin density in nitroxides

The influence of alkyl substitution on the spin density distribution in nitroxide radicals is studied by performing ab initio UHF calculations on a series of radicals from H2NO to C5H10NO. Comparison of spin populations and spin density maps in the series shows a net spin migration from oxygen to nitrogen when hydrogens are replaced by methyl groups. This result does not depend on the size of the alkyl substituents. The substitution effect explains in part the discrepancy between the theoretical spin density in H2NO and the experimental result obtained by polarized neutron diffraction on tanol suberate biradical C8H12O4((CH3)4C5H5NO)2.

The photoelectron spectra of methyl-substituted allenes and of tetramethyl-bisallenyl

The split Δ = 0.6 eV of the first band at 10.5 eV in the photoelectron spectrum of allene ( 1) has been ascribed to a Jahn—Teller distortion by Baker and Turner. The influence of alkyl substitution on Δ and on the band position has been investigated by recording the photoelectron spectra of all methyl-substituted allenes 2 to 6, of 1,1-di-tert. butyl-allene ( 7) and of 1,2-cyclononadiene ( 8). It is shown that the dependence of Δ on substitution can be rationalized by assuming that it is due to a (pseudo) Jahn—Teller effect in 1 and in the symmetrically substituted derivatives and to the combined influence of this effect and a differential, inductive destabilization in the other cases. The photoelectron spectrum of tetramethyl-bisallenyl 9 can be explained on the basis of known parameters for semi-localized π-orbitals and for their through-space and through-bond coupling.

The photoelectron spectra of methyl-substituted allenes and of tetramethyl-bisallenyl

The split Δ = 0.6 eV of the first band at 10.5 eV in the photoelectron spectrum of allene (1) has been ascribed to a Jahn—Teller distortion by Baker and Turner. The influence of alkyl substitution on Δ and on the band position has been investigated by recording the photoelectron spectra of all methyl-substituted allenes 2 to 6, of 1,1-di-tert. butyl-allene (7) and of 1,2-cyclononadiene (8). It is shown that the dependence of Δ on substitution can be rationalized by assuming that it is due to a (pseudo) Jahn—Teller effect in 1 and in the symmetrically substituted derivatives and to the combined influence of this effect and a differential, inductive destabilization in the other cases. The photoelectron spectrum of tetramethyl-bisallenyl 9 can be explained on the basis of known parameters for semi-localized π-orbitals and for their through-space and through-bond coupling.

The ionisation functions of some cyanoacetic acids

The thermodynamic functions of ionisation of dimethylcyanoacetic and isopropylcyanoacetic acids from 5 to 45 °C have been determined by an improved conductance method. The data for four cyanoacetic acids are compared in relation to the influence of alkyl substitution and the operation of the compensation law.

Influence of structural factors on the spectral and luminescence properties of metalloporphyrins

On the basis of a study of the influence of alkyl substitution on the absorption spectra of metalloporphyrins, the nodal properties of the optical π electrons, obtained in the MOLCAO method, have been confirmed. It has been established that alkyl substituents have a comparatively marked influence on the phosphorescence yield. In a study of the influence of additional complex formation on the phosphorescence, it has been shown that the effect of conjugation plays a significant part in removing the intercombination exclusion when heavy atoms are present in the molecule. It has been concluded that the D4h symmetry of the conjugated system is preserved approximately in the pyridinates of Mg porphyrins. Phosphorescence of associates of Cu porphyrins has been detected.

CONFORMATIONAL EQUILIBRIA IN OPEN-CHAIN α,β-UNSATURATED KETONES

The infrared and Raman spectra of trans-Δ3-penten-2-one have been measured over the temperature range +30° to −75° and +85° to +5° respectively. The temperature-dependent changes observed in the spectra indicate that this ketone exists as an equilibrium mixture of s-cis and s-trans conformational isomers in the liquid state. The s-trans form is the more stable and is present exclusively in the crystalline solid.Similar measurements have been carried out on Δ3-buten-2-one. The infrared and Raman spectra of this ketone also exhibit temperature effects that can be explained by a similar equilibrium, though the evidence is not as conclusive as for trans-Δ3-penten-2-one.The influence of alkyl substitution at the α- and β-carbon atoms on the relative stability of the s-cis and s-trans forms of α,β-unsaturated ketones is discussed.

Rearrangement of α-Aminoketones during Clemmensen Reduction. V. Influence of Alkyl Substitution on the α-Carbon1,2,3

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRearrangement of α-Aminoketones during Clemmensen Reduction. V. Influence of Alkyl Substitution on the α-Carbon1,2,3Nelson J. Leonard and Eric Barthel Jr.Cite this: J. Am. Chem. Soc. 1950, 72, 8, 3632–3635Publication Date (Print):August 1, 1950Publication History Published online1 May 2002Published inissue 1 August 1950https://doi.org/10.1021/ja01164a087RIGHTS & PERMISSIONSArticle Views161Altmetric-Citations20LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (498 KB) Get e-Alerts Get e-Alerts