Number Of Methyl Substituents Research Articles

Substituent effect on superoxide elimination from peroxyl radicals of adenine and methylated derivatives

The hydroxyl radical, generated by UV photolysis of 4-mercaptopyridine-N-oxide, was made to react with adenine and several methylated derivatives. The formation of the corresponding 8-hydroxy derivatives was observed in all cases and is the result of the oxidation of the respective 8-hydroxyl adducts. When this oxidation is carried out by molecular oxygen, an intermediate peroxyl radical is formed by addition of O 2 at C(4). Superoxide anion is eliminated from the peroxyl radical, followed by deprotonation, resulting in the formation of 8-hydroxyadenines (8-oxo-7,8-dihydroadenines) as the final stable products. The extent of superoxide elimination, as compared to other processes by which peroxyl radicals decay, was found to increase with the number of methyl substituents at either N 6 or N(9). This indicates that positive charge is developed in the transition state, as suggested by the negative ρ value of the Hammett relationship for this reaction.

Regarding the Structures and Fluxionality of Tricyclopentadienylaluminum Compounds

X-ray crystallographic studies, low-temperature 1H and 13C NMR studies, and 27Al NMR studies of a series of homoleptic tricyclopentadienylaluminum compounds [(C5H5)3Al (1), (MeC5H4)3Al (2), (1,2,4-Me3C5H2)3Al (3), (1,2,3,4-Me4C5H)3Al (4)] are reported along with ab initio calculations on model cyclopentadienylaluminum compounds. The ring-coordination geometries exhibited by the tricyclopentadienylaluminum compounds in the solid state vary with the number of methyl substituents on the cyclopentadienyl rings. The X-ray crystal structure of compound 1 revealed two unique molecules in the unit cell, one with an {η2, η1.5, η1.5} combination of ring geometries and the other with an {η2, η1.5, η1} combination of ring-coordination geometries. In the crystal structure of compound 3, one cyclopentadienyl ring is coordinated η5 to the aluminum while the other two rings are η1. Compound 4 exhibits monohapto coordination of all three tetramethyl-substituted cyclopentadienyl rings in the solid state. These compounds are highly fluxional in solution and exhibit averaged 1H and 13C NMR spectra in the fast-exchange limit at temperatures as low as −110 °C. This behavior is explained by the ab initio calculations on model cyclopentadienylaluminum compounds which reveal almost negligible (1−2 kcal/mol) energy differences between different ring hapticities (η1, η2, η3, η5).

Synthesis and structure-activity relationship of methyl-substituted indolo[2,3-b]quinolines: novel cytotoxic, DNA topoisomerase II inhibitors.

In furtherance of our SAR study on the chemistry and antitumor activity of fused nitrogen heteroaromatic compounds, a series of linear, methyl-substituted derivatives of 5H- and 6H-indolo[2,3-b]quinolines were synthesized according to the modified Graebe-Ullmann reaction. To establish the relationship between the physicochemical and biological activities of indolo[2,3-b]quinolines, their lipophilic properties, cytotoxic and antimicrobial activity, and ability to induce topoisomerase II dependent pSP65 DNA cleavage in vitro were investigated. We found that the antimicrobial and cytotoxic activity of indolo[2,3-b]quinolines was strongly influenced by the position, and the number of methyl substituents and the presence of methyl group at pyridine nitrogen was essential for the cytotoxicity of these compounds. All indolo[2,3-b]quinolines belonging to the 5H series, i.e., bearing a methyl group on the pyridine nitrogen, showed significant activity against procaryotic and eucaryotic organisms. They inhibited the growth of Gram-positive bacteria and pathogenic fungi at MIC range 3 x 10(-2) to 2.5 x 10(-1) mumol/mL, displayed cytotoxicity against KB cells ID50 in the range 2 x 10(-3) to 9 x 10(-3) mumol/mL, and stimulated the formation of calf thymus topoisomerase II mediated DNA cleavage at concentration between 0.4 and 10 microM. None of the indolo[2,3-b]quinolines belonging to the 6H series, i.e., lacking a methyl group on the pyridine nitrogen, was active in analogous tests. Of the investigated compounds, the most active was 2,5,9,11-tetramethyl-5H-indolo[2,3-b]quinoline, a compound bearing the highest number of symmetrically distributed methyl groups. The interaction of indolo[2,3-b]quinolines with DNA was studied by measuring the increase of calf thymus DNA denaturating temperature (Tm). The delta Tm values for the 5H series were found to be about 10 times as high as those for the 6H compounds. Indolo[2,3-b]quinolines with the highest number of methyl groups had the greatest contribution to the increase in the Tm of calf thymus DNA. The values of delta Tm reached 19 degrees C and 1.6 degrees C for the most substituted compounds of both series.

Highest Co III-Co II redox potential in Co IIN 6 ( S = [formula omitted]) complexes of tridentate ligands. Predominance of steric over electronic effect

Using the tridentate ligand 2,6-bis(pyrazol-l-ylmethyl)pyridine and its methyl-substituted derivatives a new group of high-spin grossly octahedral cobalt(II) complexes has been synthesized and characterized. The field strength of these ligands with high-spin cobalt(II) progressively decreases with an increase in the number of methyl substituents near the donor site, as revealed from their crystal-field spectral analysis. The trends in the anodic peak potentials (Co III-Co II couple with E 1 2 / E pa values of 0.78–1.06 V vs S.C.E.) are rationalized on the basis of predominance of the steric effect over the electronic effect of the methyl groups present near the donor site.

Substrate specificity of CTP: phosphocholine cytidyltransferase

The specificity of CTP:phosphocholine cytidylyltransferase from rat liver for phosphorylated bases has been investigated. The apparent Km for phosphocholine was 0.17 mM. As the number of methyl substituents on the phospho-base decreased, the apparent Km increased: 4.0 mM for phosphodimethylethanolamine, 6.9 for phosphomonomethylethanolamine and 68.4 for phosphoethanolamine. The Vmax for the reaction was similar for phosphocholine (12.6 mumol/min per mg protein), phosphomonomethylethanolamine (13.5 mumol/min per mg protein) and phosphoethanolamine (9.2 mumol/min per mg protein). When phosphodimethylethanolamine was the substrate, the Vmax was 3-fold higher (40.3 mumol/min per mg protein). Phosphoethanolamine, phosphomonomethylethanolamine and phosphodimethylethanolamine were competitive inhibitors of the cytidylyltransferase when phosphocholine was used as substrate with Ki values of 18.5 mM, 9.3 mM and 1.5 mM, respectively. The results show that the cytidylyltransferase is highly specific for phosphocholine.

ChemInform Abstract: Novel Ligands Designed for Selective Complexation of Small Cations

A variety of branched or macrocyclic polyether ligands of 1,s- dioxa type have been synthesized. Unsubstituted 12-crown-3 shows the strongest complexation, but lithium selectivity is lost due to the possi- bility of sandwich complexation of other cations. To sustain strong com- plexation of lithium, and to retain selectivity by preventing sandwich formation, it is necessary to introduce ligating side arms and to keep the number of methyl substituents as low as possible.

Synthesis of fluorine analogues of vitamin e

The biological activity of Vitamin E is believed to be related to the anti-oxidative property of the 6-chromanol structure. Vitamin E comprises a number of isomers, with differences in the number of methyl substituents on the benzene ring and the structure of the side chain at the 2-position. Vitamin E is believed to combine with the cell membrane and to suppress the oxidation of unsaturated fatty acids on the membrane. If this is correct, the differences of activity of Vitamin E compounds must be attributed to differences in their affinity for the membrane besides difference of the electronic property of the 6-chromanol part. Thus, we synthesized analogues of Vitamin E with fluorine substituents on the side chain or on the benzene ring, since these substituents might change the lipophilicity and/or the electronic property of Vitamin E.Synthesis of these analoques and their biological properties will be presented.

A spectroscopic study of bis(η 6-arene)iron(II) salts

A number of bis(η 6-arene)iron(II) salts have been synthesised from the following ligands: benzene, toluene, ethylbenzene, ortho, meta and para xylenes, mesitylene, 1,2,3,4-tetramethylbenzene, 1,2,3,5-tetramethylbenzen, 1,2,4,5-tetramethylbenzene, pentamethylbenzene, and hexamethylbenzene. The stabilities of these complexes in solution vary considerably both with solvent basicity and the degree of alkyl substitution. 1H and 13C NMR data are reported. The observed large upfield shifts of ligand 13C signals is discussed in terms of shielding by the d z 2 electrons of the central iron atom. 13C shifts correlate reasonably well with the total charge density at the relevant carbon atom for a variety of sandwich complexes, including those discussed in this work. 57Fe Mössbauer data are presented; quadrupole splittings increase systematically with the number of methyl substituents on the ligands. These changes are explained in terms of imbalances in the electronic population of metal-based e 2 and ligand-based e 1 orbitals.

Novel ligands designed for selective complexation of small cations

Abstract

MINDO-Forces Study of Methyl Substituted Allyl Cations

MINDO-Forces calculations have been performed on methyl substituted allyl cations with complete energy minimization. It was found that the methyl substitution on the terminal carbon atoms of the allyl cation stabilizes the cation more than that at the center carbon atom. Also, the stability of the cation depends on the conformation of the cation and not on the number of methyl substituents.

Chemical changes of organic compounds in chlorinated water : XII. Gas chromatographic—mass spectrometric studies of the reactions of methylnaphthalenes with hypochlorite in dilute aqueous solution

The products of aqueous chlorination reactions of naphthalene, 1- and 2-methylnaphthalenes, 1,2-, 1,3-, 1,4-, 1,5-, 1,8-, 2,3- and 2,6-dimethylnaphthalenes and 2,3,5-trimethylnaphthalene with hypochlorite have been determined by gas chromatography—mass spectrometry. They included chloro-substituted, oxygenated (quinones) and hydroxylated (phenols) compounds which were readily formed at room temperature. The extent of the reactions was shown to depend on the pH, the initial concentrations of both compounds and the number of methyl substituents and their positions. Monochlorinated compounds were identified in the chlorinated water under those conditions utilized for water treatment.

Formation of crystalline complexes between polymethylated quinones and hydroquinones

The effect of increased substitution by methyl groups on the formation of solid-state complexes of quinones with hydroquinones has been investigated. Both the ease and the stoicheiometry of complex formation of di-, tri-, and tetra-methylated quinones with hydroquinones, either by ‘solid–solid’ reaction or by recrystallization from a solvent, has been found to depend in part on the number of methyl substituents on each component. When there is methyl substitution on the hydroquinone moiety, a complex with components in 1 : 1 ratio is generally formed, while with methyl groups on the quinone molecule the ratio of quinone to hydroquinone in the complex is generally 1 : 2.Furthermore the ease of complex formation can be highly structure-sensitive. Thus, although 1,4-benzoquinone reacts readily with 2,3,5,6-tetramethylhydroquinone to give a 2 : 1 complex, 2,3,5,6-tetramethylbenzoquinone and hydroquinone do not react when the two solids are ground together, crystallized from a solvent by the conventional procedure, or kept for long periods in contact with each other. Reaction of the two solids ground together can, however, be induced by heating the mixture at 80 °C; this is a convenient preparative method for the 1 : 1 product. Furthermore, seeding the solid mixture of the quinone and hydroquinone by addition of a small amount of the 1 : 1 product induces solid–solid reaction. Finally, a 1 : 2 complex of duroquinone with hydroquinone is formed when an ethyl acetate solution saturated with and containing an excess of each component suspended in the mixture is seeded with crystals of either the 1 : 1 or 1 : 2 complex. Similarly 2,5-dimethyl-1,4-benzoquinone can be induced to form both a 1 : 1 and a 2 : 1 complex with 2,5-dimethylhydroquinone.

Titrations in non-aqueous media. Part IV. Solvent effects on basicity of aliphatic amines

The relative basicity orders of methyl-, ethyl-, propyl- and butylamines have been measured potentiometrically with perchloric acid in cyclohexane and hexane solvents. The basicity orders of the amines in the series, including ammonia, were found to be NH3 > MeNH2 > Me2NH > Me3N; NH3 > EtNH2 > Et2NH > Et3N; NH3 > n-PrNH2 > n-Pr2NH > n-Pr3N; NH3 > n-BuNH2 > n-Bu2NH > n-Bu3N; and n-BuNH2 > i-BuNH2 > sec-BuNH2 > t-BuNH2. In addition to these, some interesting orders have also been found among primary, secondary and tertiary amines, e.g., MeNH2 > EtNH2 > n-PrNH2 > n-BuNH2; Me2NH > Et2NH > n-Pr2NH > n-Bu2NH; Me3N > Et3N > n-Pr3N > n-Bu3N; and MeNH2 > EtNH2 > i-PrNH2 > t-BuNH2. From these findings four important results have been obtained as follows: (1) an increase in the number of alkyl group decreases the basicity; (2) an increase in the size of an alkyl group decreases the basicity; (3) amines containing unbranched alkyl groups are more basic than their branched analogues; and (4) an increase in the number of methyl substituents on the methyl group of methylamine decreases the basicity in a regular manner. These results contradict results reported in the literature and also earlier results obtained in this laboratory.

The gas phase reactions of the trichloromethylium ion with alkyl aromatics, studied by high pressure mass spectrometry

The reactions of trichloromethylium (CCl3+) with benzene and the lower alkyl aromatics (ArH) have been studied by high pressure mass spectrometry at pressures in the range 2–4 Torr and temperatures from 300 to 560 K. The only two primary products are the adduct ArHCCl3+ and ArCCl2+, which is formed by loss of HCl from the adduct. The relative yields of adduct increase with increasing number of methyl substituents on the aromatic ring (benzene → mesitylene). The disappearance of CCl3+ is kinetically second order with specific rate constants increasing from benzene to mesitylene, the latter reacting essentially at every ion–molecule collision. All rate constants are fairly large (>1010 cc molecule−1 s−1) and show negative temperature coefficients. ArCCl2+ is unreactive but ArHCCl3+ reacts further by proton transfer to ArH.

Reactivity of Organic Ions by Chemical Ionization Mass Spectrometry. II. Chemical Ionization Mass Spectra of Alkylbenzenes with Methane by Using a Quadrupole Mass Spectrometer

Abstract The titled spectra have been determined at 75 °C. The (M+H)+ ion intensities for methylbenzenes decrease linearly with the number of methyl substituents. The (M+H)+ ion intensities for dialkylbenzenes decrease in the order o->m->p-, while those of trimethylbenzenes decrease in the order 1,2,3-> 1,3,5->1,2,4-, and those of tetramethylbenzenes decrease in the order 1,2,3,4->1,2,3,5->1,2,4,5-.

Plant Sterol Metabolism: ENZYMATIC CLEAVAGE OF THE 9β,19β-CYCLOPROPANE RING OF CYCLOPROPYL STEROLS IN BRAMBLE TISSUE CULTURES

A cell-free enzyme preparation obtained from bramble tissues (Rubus fruticosus) grown in vitro was found to be capable of opening the cyclopropane ring of cycloeucalenol, producing obtusifoliol. The identification of this substance was based on the use of radiochromatography, formation of functional derivatives, and crystallization to constant specific radioactivity. A boiled preparation failed to mediate the reaction, proving that the opening of the 9β,19β-cyclopropane ring is enzymatic. Enzymatic activity was bound to the microsomal fraction and was not dependent upon the addition of exogenous ATP or NADH. Microsomes from other higher plant species (germinating peas and tobacco tissue cultures) were found to be active in transforming cycloeucalenol into obtusifoliol, but microsomes from rabbit liver were unable to perform this reaction. 24-Methylene cycloartanol, cycloartenol, and cycloeucalenol, which are ubiquitous constituents of higher plants, were tested as substrates for the enzymatic reaction. The 4,4-dimethyl sterols are very poor substrates, whereas cycloeucalenol is efficiently converted. In a second group of experiments, three substrates differing only by the number of methyl substituents in position 4 were incubated with the microsomal fraction. Cycloeucalenol (a 4α-methyl sterol) and 24-methylene pollinastanol (a 4-desmethyl sterol) were converted to obtusifoliol and 4-desmethyl obtusifoliol, respectively. But 24-methylene cycloartanol (a 4,4-di-methyl sterol) was not transformed, which suggests that the 4β-methyl group hinders this reaction. On the basis of the results obtained, a tentative mechanism for the opening of the cyclopropane ring is proposed.

Polybenzyl polymers I. The effect of monomer structure on polymer properties

AbstractA systematic study has been made of the effect of methyl substitution in the aromatic ring on the FRIEDEL‐CRAFTS polycondensation of p‐dichloromethylbenzene and its derivatives with benzene derivatives. When the total number of methyl groups on the monomer and comonomer is four or greater, highly crystalline, low molecular weight products are formed. When the number of methyl substituents is less than four, rapid polymerization occurs to give amorphous, cross‐linked materials. By careful control of reaction conditions, however, the latter reactions can be stopped before cross‐linking takes place and relatively high‐molecular weight, non‐cross‐linked polymers can be isolated.

A New Tetramethylbutadiene

Abstract The present investigation was undertaken largely as part of a study of the influence of methyl substitution on the polymerizability of butadiene. The data available on the way in which and the extent to which polymerization is affected by the position and the number of methyl groups which may be introduced as substituents into the molecule of butadiene are far from complete. Both the a- and the b-methylbutadienes are polymerizable to rubbers. Of the dimethylbutadienes, the bg- and ad- are polymerizable; the gem-dimethyl compound appears, according to observations of Kyriakides and others, to be polymerizable, but according to a statement of Harries only with difficulty. It would appear that methyl substitution in the terminal positions of butadiene has, compared with such substitution in the middle positions, an unfavorable effect on the ease of polymerization. It would appear, further, from the limited data available, that increase in the number of methyl substituents in butadiene diminishes the ease of polymerization, since bg-dimethylbutadiene polymerizes less easily than isoprene and ad-dimethylbutadiene less easily than piperylene. The available information regarding the polymerizability of tri- and tetramethylbutadienes is very meagre. The known trimethylbutadienes (aag- and aad-) have not been studied from the point of view of polymerization. From its behavior on distillation, Pribytek considered aadd-tetramethylbutadiene (diisocrotyl) to show an inclination to polymerize, and it has been mentioned in the patent literature as polymerizable. Lebedeff, however, found it to be practically lacking in ability to polymerize when heated at temperatures up to 250. Another tetramethylbutadiene which has been described, viz., the aagd-compound, has not been studied in regard to polymerization.