Effects Of Ring Substituents Research Articles

Binding Interaction of the Trimethylsilyl Cation with Oxygen and Nitrogen Bases in the Gas Phase. Acetopheones, Benzaldehydes, Pyridines, Anilines, and N,N-Dimethylanilines

Abstract The gas-phase basicities toward the trimethylsilyl cation, GB(Me3Si+), were determined for a series of acetophenones, benzaldehydes, pyridines, anilines, and N,N-dimethylanilines by measuring the equilibrium constants of trimethylsilyl cation transfer reactions. GB(Me3Si+) increases in the order aniline < benzaldehyde < acetophenone < N,N-dimethylaniline < pyridine, while GB(H+) increases as benzaldehyde < acetophenone < aniline < pyridine < N,N-dimethylaniline. The effects of ring substituents on the GB(Me3Si+) of the respective bases are, however, linearly correlated with the corresponding proton basicities with a slope of 0.8 to 1.0, showing family-dependent linear relationships. Furthermore, an analysis of the substituent effects on the GB(Me3Si+) of acetophenone and benzaldehyde showed that the ρ values are close to those for the proton basicities, though the resonance demand of Me3Si+ adduct ions is slightly reduced compared with that for the protonated ones. DFT calculations at the B3LYP/6-31+G(d) level of theory reproduced such a trend in substituent effects as well as the family-dependent linear correlations between the H+ and Me3Si+ basicities. Both the experimental and theoretical results lead to the conclusion that the binding interactions of Me3Si+ with O and N atoms of organic bases have a pronounced covalent character to a similar degree as that of a proton.

QSARs of some novel isosteric heterocyclics with antifungal activity.

QSAR analysis of a set of previously synthesized 2,5,6-trisubstituted benzoxazole, benzimidazole and 2-substituted oxazolo(4,5-b)pyridine derivatives tested for growth inhibitory activity against Candida albicans, was performed by using the computer-assisted multiple regression procedure. The activity contributions for either heterocyclic ring systems or substituent effects of these compounds were determined from the correlation equation and the predictions for the lead optimization were described. The resulting QSAR revealed that the oxazolo(4,5-b)pyridine ring system with the substitution of a benzyl moiety at position 2 was the most favourable structure among the heterocyclic nuclei. Moreover, the fifth position in the fused ring system is found more significant than the other positions in improving the activity.

Kinetic characterization of the substrate specificity and mechanism of mushroom tyrosinase.

This paper reports a quantitative study of the effect of ring substituents in the 1-position of the aromatic ring on the rate of monophenol hydroxylation and o-diphenol oxidation catalyzed by tyrosinase. A possible correlation between the electron density of the carbon atom supporting the oxygen from the monophenolic hydroxyl group and the V Mmax values for each monophenol was found. In the case of o-diphenols the same effect was observed but the size of the side-chain became very important. NMR studies on the monophenols justified the sequence of the V Mmax values obtained. As regards the o-diphenols, on the other hand, only a fair correlation between NMR and V Dmax values was observed due to the effect of the molecular size of the ring substituent. From these data, it can be concluded that the redox step (k33) is not the rate-determining step of the reaction mechanism. Thus, the monophenols are converted into diphenols, but the order of specificities towards monophenols is different to that of o-diphenols. The rate-limiting step of the monophenolase activity could be the nucleophilic attack (k51) of the oxygen atom of the hydroxyl group on the copper atoms of the active site of the enzyme. This step could also be similar to or have a lower rate of attack than the electrophilic attack (k52) of the oxygen atom of the active site of oxytyrosinase on the C-3 of the monophenolic ring. However, the rate-limiting step in the diphenolase activity of tyrosinase could be related to both the nucleophilic power of the oxygen atom belonging to the hydroxyl group at the carbon atom in the 3-position (k32) and to the size of the substituent side-chain. On the basis of the results obtained, kinetic and structural models describing the monophenolase and diphenolase reaction mechanisms for tyrosinase are proposed.

Ethene polymerization with mixed-ring metallocene catalysts, Cp′Cp″MCl2, M = Ti and Zr

Mixed-ring metallocenes Cp′Cp″MCl2 (Cp′ and Cp″ = cyclopentadienyl and its substituted derivatives; M = Ti and Zr) have been prepared by reacting Cp′MCl3 with the Cp″ anion salt, in which the Cp′–M bond is stronger than the Cp″–M bond. Ethene has been polymerized with these complexes in the presence of methyl aluminoxane (MAO) as co-catalyst. The catalytic properties of titanocenes were influenced mainly by the steric effects of cyclopentadienyl ring substituents. Both steric and electronic effects of substituents influenced the catalytic properties of zirconocenes.

Substituent effects on the O–H bond dissociation enthalpies in phenolic compounds: agreements and controversies + erratum

Abstract

Monophenolase and Diphenolase Reaction Mechanisms of Apple and Pear Polyphenol Oxidases

This paper reports a quantitative study of the effect of ring substituents on the rate of monophenol hydroxylation and o-diphenol oxidation catalyzed by apple and pear polyphenol oxidases. A good correlation between the electronic density at the carbon atom in the 4-position of the aromatic ring for each monophenol and the Vmax values was found. However, this correlation was not so good in the 3- and 4-positions for the o- diphenols assayed. NMR studies on the monophenols demonstrated the higher reactivity of 4-hydroxyanisole compared with the other monophenols assayed. Catechol was the best o-diphenolic substrate assayed because of the absence of a ring substituent. All of these data confirmed the proposed enzyme's reaction mechanism and indicate that the rate- limiting step in the monophenolase reaction mechanism could be the nucleophilic attack of the oxygen atom belonging to the hydroxyl group at the carbon atom in the 4-position on the copper atoms of the enzyme's active site. However, in the diphenolase reaction mechanism, the rate-limiting step could be related to both the nucleophilic attack of the oxygen atom from the hydroxyl group at the carbon atom in the 3-position on the copper atoms of the enzyme's active site and the molecular size of the substituent side chain. Keywords: Diphenolase; enzyme kinetics; MBTH; monophenolase; NMR; PPO

Conformational Preferences of 2-Phenethylamines. A Computational Study of Substituent and Solvent Effects on the Intramolecular Amine−Aryl Interactions in Charged and Neutral 2-Phenethylamines

A computational investigation of the conformational preferences of 2-phenethylamine has been carried out with a variety of techniques. To determine the intrinsic (in the absence of a solvent medium) conformational preferences of the 2-phenethylamine system, ab initio calculations at various levels of theory up to the MP2/6-311+G(d,p)//MP2/6-31G(d,p) level were carried out. This is the most sophisticated level of theory that has been applied to this biologically important system to date. In the absence of a solvent medium, phenethylamines prefer a folded gauche conformation for both the charged and neutral amines, indicating a favorable interaction between the amino group and the aromatic ring. To probe the nature of this intramolecular interaction further the effects of ring substituents on the conformational preferences were studied. The results have been compared to those obtained with semiempirical and molecular mechanics force field methods. The molecular mechanics force fields employing default param...

Ring Size, Substituent, and Anion Effects on the Kinetic and Equilibrium Properties of Copper(II) Complexes with Water-Soluble Macrocyclic Tetrathia Ethers

The complete series of alcoholic derivatives for the 13- through 16-membered macrocyclic tetrathia ethers, in which a single −OH group is attached to the central carbon of a trimethylene bridge, ha...

Effect of Ring Substituents on Formation Rates for Vanadium−Arene Clusters

Vanadium−arene complexes, Vn(arene)m (arene = benzene (C6H6), toluene (C6H5CH3), and fluorobenzene (C6H5F)), were synthesized by the reaction of laser-vaporized vanadium atoms with arene vapor. Both the analysis of the mass spectra and the measurements of their ionization energies indicate that both Vn(C6H5CH3)m and Vn(C6H5F)m clusters take a multiple-decker sandwich structure similar to the structure of Vn(C6H6)m clusters. The relative reactivity between benzene and toluene toward vanadium was also determined; toluene is 4 times as reactive as benzene for V1(C6H5CH3)1/V1(C6H6)1 production and 2 times for V1(C6H5CH3)2/V1(C6H6)2 production because of reactivity enhancement of the electron-donating ring substituent. In the case of the Vn(C6H5F)m cluster, it is found that the electron-withdrawing ring substituent of fluorobenzene results in much less reactivity than is observed for benzene and toluene.

Gas-Phase Substituent Effects in Stabilized Benzylic Carbocations. Basicities of Benzaldehydes, Acetophenones, and Methyl Benzoates in the Gas Phase

Abstract The gas-phase basicities of a series of aromatic carbonyl compounds (ArCOR; R = OMe, Me, H) were measured based on the proton-transfer equilibrium method using a pulsed ICR mass spectrometer. The effects of ring-substituents on the gas-phase basicities were analyzed in terms of the Yukawa–Tsuno equation. It was shown that the resonance demand parameter (r+) decreases significantly from 1.06 for the benzaldehyde to 0.50 for the methyl benzoate in increasing order of the electron-donating ability of the R group directly linked to the carbonyl carbon. This indicates that the π-charge formed in the conjugate acid ion is competitively delocalized into an aryl group and an R group. In contrast, the ρ value is nearly constant at −11 (in kcal mol−1 per σ unit) in all series. Most importantly, it was found that the r+ value in the gas phase is in agreement with that for the basicities in aqueous solution, whereas the ρ value is significantly reduced in aqueous solution. This fact led us to the conclusion that the solvation of a cation reduces the central charge so as to lower the response to substituent perturbation, essentially without changing the nature of the intramolecular charge-delocalization.

Adsorption of Catechols, 2-Aminophenols, and 1,2-Phenylenediamines at the Metal (Hydr)Oxide/Water Interface: Effect of Ring Substituents on the Adsorption onto TiO2

The extent of adsorption and the value of the adsorption equilibrium constant (Ksintr) for simple organic ligands is influenced by the identity of the ligand donor groups and other substituents on the aromatic ring. Catechols adsorb onto TiO2 to a significantly greater extent than 2-aminophenols; the adsorption of 1,2-phenylenediamines is negligible. The TiO2 surface has a high ionic contribution to bonding; ligands possessing donor groups with the highest ionic contribution to bonding adsorb to the greatest extent. A covalent contribution to bonding can increase binding to Ti(IV)-containing surfaces, but only when the ionic contribution is already strong. Within each ligand class, substituents alter the competition between protons and surface sites for binding the deprotonated ligand. For this reason, pKa1, pKa2, and log Ksintr are all important in determining the extent of adsorption. Additionally, substituents that impart hydrophobicity also raise the extent of adsorption and the value of log Ksintr.

Stereochemical Effects in the Mass Spectra ofcis-andtrans-2-Aryl-4a,5,6,7,8,8a-hexahydroquinazolin-4(3H)-ones

The electron-impact (EI) and collision-induced dissociation (CID) spectra of the title compounds were studied. The main fragmentation routes of M+· ions included losses of hydrocarbon species and the formation of ArCNH+ cations. The geometry of ring annelation predictably affected the stabilities of the molecular ions and the relative abundances of some characteristic fragment ions. The abundance ratios [M−H]+/M+·, which were higher for trans-annelated isomers, correlated with the electronic effects of aromatic ring substituents. Molecular ions and [M−H]+ ions of stereoisomers gave different CID spectra, suggesting that stereochemical differences are still preserved after the loss of hydrogen from M+· ions. The stereochemical effects in the EI spectra were more pronounced at lower impact energies (16–24 eV). Several criteria for differentiating cis- and trans-annelated isomers based on the relative abundances of characteristic fragment ions were established.

Acid Catalyzed Hydrolysis of Ciclic Benzophenone Acetals. Effects of Ring Size and Ring Substituent

Acid Catalyzed Hydrolysis of Ciclic Benzophenone Acetals. Effects of Ring Size and Ring Substituent

Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker.

We have previously described the potent and selective inhibition of several strains of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) by JM2763, an n-propyl-linked dimer of the 1,4,8,11-tetraazamacrocyclic (cyclam) ring system. Upon further investigation, we have also found that incorporating an aromatic rather than aliphatic linker leads to analogs with higher antiviral potency. The prototype, JM3100 (19a, isolated as the octahydrochloride salt), which contains a p-phenylenebis(methylene) moiety linking the cyclam rings, inhibited the replication of HIV-1 (IIIB) and HIV-2 (ROD) at EC50's of 4.2 and 5.9 nM, respectively, while remaining nontoxic to MT-4 cells at concentrations exceeding 421 microM. In order to identify the structural features of bis-tetraazamacrocycles required for potent activity, we have prepared a novel series of phenylenebis(methylene)-linked analogs, in which the macrocyclic ring size was varied from 12 to 16 ring members. Depending upon the substitution of the phenylenebis(methylene) linker (para or meta), sub-micromolar anti-HIV activity was exhibited by analogs bearing macrocycles of 12-14 ring members but with varying cytotoxicity to MT-4 cells. Furthermore, while we found that identical macrocyclic rings are not required for activity, substituting an acyclic polyamine equivalent for one of the cyclam rings in 19a resulted in a substantial reduction in anti-HIV potency, clearly establishing the importance of the constrained macrocyclic structure. A short series of transition metal complexes of 19a were also prepared and evaluated. Complexes of low kinetic stability such as the bis-zinc complex retained activity comparable to that of the parent compound. Finally, the activity of bicyclam analogs appears to be insensitive to the electron-withdrawing or -donating properties of substituents introduced onto the linker, but sterically hindering groups such as phenyl markedly reduced activity. As a result, several analogs with anti-HIV potency comparable to that of 19a have been identified.

Microscale Electrophilic Aromatic Substitution of p-Toluidine

Experimental procedure for first-year organic chemistry students to apply the principles of group protection and study the effect of ring substituents on reaction orientation.

Anti-allergy agents. 3. Angular tricyclic ether derivatives of the 1,8-naphthyridin-2(1H)-one ring system

The compounds described are potent, orally active inhibitors of the release of the leukotriene mediators of anaphylaxis in vitro and in vivo. Unlike most “Mediator Release Inhibitors” (MRI's) described in the literature, they do not contain an acidic function. A series of potent, orally-active inhibitors of leukotriene release has been synthesized and tested in vitro and in vivo. The effects of ring size and substituents on anti-allergic activity have been examined.

Computational study of the hydrolysis of degradable polysaccharide biomaterials: Substituent effects on the hydrolytic mechanism

AbstractHyaluronic acid and its derivatives are absorbable polysaccharides which are used extensively in cosmetics and as biomaterials. Two possible mechanisms of degradation, involving an oxocarbenium ion and the corresponding radical cation, are examined by modeling of the saccharide ring and the effects of various ring substituents on the two possible mechanisms. © 1994 by John Wiley & Sons, Inc.

Electron-Transfer Kinetics of Copper(II/I) Complexes with Dialcoholic Derivatives of the Macrocyclic Tetrathiaether [14]aneS4. Effect of Simple Ring Substituents upon Gated Behavior

Studies have been conducted on the electron-transfer kinetics of the Cu(II/I) complexes formed with two dialcoholic derivatives of the macrocyclic tetrathiaether [14] aneS 4 , syn- and anti-3,6,10,13-tetrathiacyclotetradecane-1,8-diol. For Cu II / I (syn-[14]aneS 4 -diol), the self-exchange rate constant has been determined directly from NMR line broadening. For both Cu II / I L systems, extensive cross-reaction electron-transfer kinetics have also been measured using four different reductants and four different oxidants, spanning a wide range of reaction potentials

Factors affecting rates of thermal decomposition of 5-azidopyrazoles: a comparison with other aromatic azides

2-Methoxyazidobenzene has been used as a model compound for α-azido five-membered heterocycles, and undergoes thermal loss of nitrogen 16 times as fast as azidobenzene and 3.6 times as fast as its para isomer. These rates identify an important electrostatic stabilization within a charge-separated transition state. It is argued that this stabilization would be very much larger in thermolyses of α-azido five-membered heterocycles and removes the need to postulate that their high rates are due to appreciable ring-opening at the transition state. Electronic effects of ring substituents in 5-azidopyrazoles are consistent with this electrostatic model. The electron distribution required is not compatible with the operation of a neighbouring group effect, and none is found for 5-azido-4-nitro-pyrazole.

QSARs of some novel antibacterial benzimidazoles, benzoxazoles, and oxazolopyridines against an enteric gram-negative rod;K. pneumoniae

A set of previously synthesized 2,5-disubstituted benzimidazole (I), benzoxazole (II), and 2-substituted oxazolo(4,5- b)pyridine (III) derivatives were tested for in vitro growth inhibitory activity against K. pneumoniae and the quantitative structure-activity relationships (QSARs) were analyzed by a computer-assisted multiple regression procedure. The activity contributions for either heterocyclic ring systems or substituent effects were determined from the correlation equations and predictions for the lead optimization were described. The resulting QSAR revealed that the oxazolo(4,5- b)pyridine ring system with the substitution of a benzyl moiety at position 2 was the most favorable structure over the other heterocyclic nuclei against K. pneumoniae. The position R in the fused ring system was found to be important for improving the activity by substitution at this position by hydrogen accepting groups with the electronic effect of negative field interactions.