Biomedical subjects

Helmi Neuvonen

Publications and source records attributed to Helmi Neuvonen.

6 recordsLinked to original sources

PubMed2006

Effect of 4-substitution on psychotomimetic activity of 2,5-dimethoxy amphetamines as studied by means of different substituent parameter scales.

Electron-withdrawing substituents at position 4 of 2,5-dimethoxy-substituted amphetamines increase, whereas electron-donating substituents decrease the psychotomimetic activity. The origin of this clearly localized effect is discussed. The uses of modified Hammett substituent scales (sigma(-) and sigma(+)), and especially the good sigma(+) correlation, strongly suggest that electron-donating substituents decrease the biological activity through a specific effect relating to the extent of the conjugative electron release from the 5-methoxy group to the phenyl ring.

Amphetamines↗

PubMed2006

Substituent cross-interaction effects on the electronic character of the C=N bridging group in substituted benzylidene anilines--models for molecular cores of mesogenic compounds. A 13C NMR study and comparison with theoretical results.

13C NMR chemical shifts delta(C)(C=N) were measured in CDCl3 for a wide set of mesogenic molecule model compounds, viz. the substituted benzylidene anilines p-X-C6H4CH=NC6H4-p-Y (X = NO2, CN, CF3, F, Cl, H, Me, MeO, or NMe2; Y = NO2, CN, F, Cl, H, Me, MeO, or NMe2). The substituent dependence of delta(C)(C=N) was used as a tool to study electronic substituent effects on the azomethine unit. The benzylidene substituents X have a reverse effect on delta(C)(C=N): electron-withdrawing substituents cause shielding, while electron-donating ones behave oppositely, the inductive effects clearly predominating over the resonance effects. In contrast, the aniline substituents Y exert normal effects: electron-withdrawing substituents cause deshielding, while electron-donating ones cause shielding of the C=N carbon, the strengths of the inductive and resonance effects being closely similar. Additionally, the presence of a specific cross-interaction between X and Y could be verified. The electronic effects of the neighboring aromatic ring substituents systematically modify the sensitivity of the C=N group to the electronic effects of the benzylidene or aniline ring substituents. Electron-withdrawing substituents on the aniline ring decrease the sensitivity of delta(C)(C=N) to the substitution on the benzylidine ring, while electron-donating substituents have the opposite effect. In contrast, electron-withdrawing substituents on the benzylidene ring increase the sensitivity of delta(C)(C=N) to the substituent on the aniline ring, while electron-donating substituents act in the opposite way. These results can be rationalized in terms of the substituent-sensitive balance of the electron delocalization (mesomeric effects). The present NMR characteristics are discussed as regards the computational literature data. Valuable information has been obtained on the effects of the substituents on the molecular core of the mesogenic model compounds.

Aniline Compounds↗

PubMed2005

Propagation of polar substituent effects in 1-(substituted phenyl)-6,7-dimethoxy-3,4-dihydro- and -1,2,3,4-tetrahydroisoquinolines as explained by resonance polarization concept.

[structures: see text] Propagation of inductive and resonance effects of phenyl substituents within 1-(substituted phenyl)-6,7-dimethoxy-3,4-dihydro- and -1,2,3,4-tetrahydroisoquinolines were studied with the aid of 13C and 15N NMR chemical shifts and ab initio calculations. The substituent-induced changes in the chemical shift (SCS) were correlated with a dual substituent parameter equation. The contributions of conjugative (rhoR) and nonconjugative effects (rhoF) were analyzed, and mapping of the substituent-induced changes is given over the entire isoquinoline moiety for both series. The experimental results can be rationalized with the aid of the resonance polarization concept. This means the consideration of the substituent-sensitive balance of different resonance structures, i.e., electron delocalization, and the effect of the aromatic ring substituents on their relative contributions. With tetrahydroisoquinolines, the delocalization of the nitrogen lone pair (stereoelectronic effect) particularly contributes. Correlation analysis of the Mulliken atomic charges for the dihydroisoquinoline derivatives was also performed. The results support the concept of the substituent-sensitive polarization of the isoquinoline moiety even if the polarization pattern achieved via the NMR approach is not quite the same as that predicted by the computational charges. Previously the concepts of localized pi-polarization and extended polarization have been used to explain polar substituent effects within aromatic side-chain derivatives. We consider that the resonance polarization model effectively contributes to the understanding of the polar substituent effects.

Journal Article↗

PubMed2005

Ab initio study of the substituent effects on the relative stability of the E and Z conformers of phenyl esters. Stereoelectronic effects on the reactivity of the carbonyl group.

Equilibria between the Z (tau1= 0 degrees) and E (tau1= 180 degrees) conformers of p-substituted phenyl acetates 4 and trifluoroacetates 5 (X = OMe, Me, H, Cl, CN, NO2) were studied by ab initio calculations at the HF/6-31G* and MP2/6-31G* levels of theory. The preference for the Z conformer, DeltaE(HF), was calculated to be 5.36 kcal mol(-1) and 7.50 kcal mol(-1) for phenyl acetate and phenyl trifluoroacetate (i.e., with X = H), respectively. The increasing electron-withdrawing ability of the phenyl substituent X increases the preference of the Z conformer. An excellent correlation with a negative slope was observed for both series between DeltaE of the E-Z equilibrium and the Hammett sigma constant. By using an appropriate isodesmic reaction, it was shown that electron-withdrawing substituents decrease the stability of both conformers, but the effect is higher with the E conformer. Electron-withdrawing phenyl substituents decrease the delocalization of the lone pair of the ether oxygen to the C=O antibonding orbital (nO--> pi*C=O) in both the E and Z forms and in both series studied; this effect is higher in the E conformer than in the Z conformer. The nO --> pi*C=O electron donation has a minimum value with tau1= 90 degrees and a maximum value with tau1= 0 degrees (the Z conformer), the value with tau1= 180 degrees (the E conformer) being between these two values, obviously due to steric hindrance. The effects of the phenyl substituents on the reactivity of the esters studied are discussed in terms of molecular orbital interactions. ED/EW substituents adjust the availability of the pi*C=O antibonding orbital to interact with the lone pair orbital of the attacking nucleophile and therefore affect the reactivity: EW substituents increase and ED substituents decrease it. Excellent correlations were observed between the rate coefficients of nucleophilic acyl substitutions and pi*C=O occupancies of the ester series 4 and 5.

Journal Article↗

PubMed2004

Evidence of substituent-induced electronic interplay. Effect of the remote aromatic ring substituent of phenyl benzoates on the sensitivity of the carbonyl unit to electronic effects of phenyl or benzoyl ring substituents.

Carbonyl carbon (13)C NMR chemical shifts delta(C)(C[double bond]O) measured in this work for a wide set of substituted phenyl benzoates p-Y-C(6)H(4)CO(2)C(6)H(4)-p-X (X = NO(2), CN, Cl, Br, H, Me, or MeO; Y = NO(2), Cl, H, Me, MeO, or NMe(2) ) have been used as a tool to study substituent effects on the carbonyl unit. The goal of the work was to study the cross-interaction between X and Y in that respect. Both the phenyl substituents X and the benzoyl substituents Y have a reverse effect on delta(C)(C[double bond]O). Electron-withdrawing substituents cause shielding while electron-donating ones have an opposite influence, with both inductive and resonance effects being significant. The presence of cross-interaction between X and Y could be clearly verified. Electronic effects of the remote aromatic ring substituents systematically modify the sensitivity of the C[double bond]O group to the electronic effects of the phenyl or benzoyl ring substituents. Electron-withdrawing substituents in one ring decrease the sensitivity of delta(C)(C[double bond]O) to the substitution of another ring, while electron-donating substituents inversely affect the sensitivity. It is suggested that the results can be explained by substituent-sensitive balance of the contributions of different resonance structures (electron delocalization, Scheme 1).

Journal Article↗

PubMed2002

Electron-withdrawing substituents decrease the electrophilicity of the carbonyl carbon. An investigation with the aid of (13)C NMR chemical shifts, nu(C[double bond]O) frequency values, charge densities, and isodesmic reactions to interpret substituent effects on reactivity.

(13)C NMR chemical shifts and nu(C[double bond]O) frequencies have been measured for several series of phenyl- or acyl-substituted phenyl acetates and for acyl-substituted methyl acetates to investigate the substituent-induced changes in the electrophilic character of the carbonyl carbon. Charge density, bond order, and energy calculations have also been performed. The spectroscopic and charge density results indicate that opposite to the conventional thinking, electron-withdrawing substituents do not increase the electrophilicity of the carbonyl carbon but instead decrease it. On the other hand, reaction energies of the isodesmic reactions designed show that electron-withdrawing substituents destabilize the carbonyl derivatives investigated. So, a significant ground-state destabilization of carboxylic acid esters, and carbonyl compounds in general, due to the decreased resonance stabilization, is proposed as a novel concept to explain both the increase in their reactivity and the changes in the chemical shifts and carbonyl frequencies induced by electron-withdrawing substituents.

Journal Article↗