Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
1.
Chemphyschem ; 22(7): 641-648, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33555663

RESUMO

We have quantum chemically investigated the rotational isomerism of 1,2-dihaloethanes XCH2 CH2 X (X = F, Cl, Br, I) at ZORA-BP86-D3(BJ)/QZ4P. Our Kohn-Sham molecular orbital (KS-MO) analyses reveal that hyperconjugative orbital interactions favor the gauche conformation in all cases (X = F-I), not only for X = F as in the current model of this so-called gauche effect. We show that, instead, it is the interplay of hyperconjugation with Pauli repulsion between lone-pair-type orbitals on the halogen substituents that constitutes the causal mechanism for the gauche effect. Thus, only in the case of the relatively small fluorine atoms, steric Pauli repulsion is too weak to overrule the gauche preference of the hyperconjugative orbital interactions. For the larger halogens, X⋅⋅⋅X steric Pauli repulsion becomes sufficiently destabilizing to shift the energetic preference from gauche to anti, despite the opposite preference of hyperconjugation.

2.
Beilstein J Org Chem ; 16: 2469-2476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093926

RESUMO

Molecular polarity governs lipophilicity, which in turn determines important agrochemical and environmental properties, such as soil sorption and bioconcentration of organic compounds. Since the C-F bond is the most polar in organic chemistry, the orientation of fluorine substituents originating from the rotation around C-C(F) bonds should affect the polarity and, consequently, the physicochemical and biological properties of fluorine-containing agrochemicals. Accordingly, this study aims to determine the most likely conformers of some fluorine-containing agrochemicals and to correlate their molecular dipole moments with the respective n-octanol/water partition coefficients (log P), in order to investigate the dependence of the lipophilicity with the molecular conformation.

3.
Ecotoxicol Environ Saf ; 199: 110679, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32402896

RESUMO

Chlordane is a worldwide banned organochlorine insecticide because of its hazard to animal and human health. It is also a persistent organic pollutant, which can affect either the soil or the aquatic life. The same applies to other chlorinated cyclodiene insecticides, such as dieldrin and aldrin. In turn, organofluorine compounds have a widespread use in agriculture. Therefore, density functional calculations and docking studies showed that the bioisosteric replacement of chlorines in the above-mentioned compounds by fluorines improves some physicochemical parameters used to estimate the toxicity and environmental risk of these compounds, as well as the ligand-enzyme (GABAA receptor-chloride channel complex) interactions related to their insecticidal activity. This work is an effort to provide an improved new class of organofluorine pesticides.


Assuntos
Hidrocarbonetos Clorados/química , Hidrocarbonetos Fluorados/química , Modelos Teóricos , Praguicidas/química , Receptores de GABA-A/química , Animais , Fenômenos Químicos , Halogenação , Humanos , Hidrocarbonetos Clorados/farmacologia , Hidrocarbonetos Clorados/toxicidade , Hidrocarbonetos Fluorados/farmacologia , Hidrocarbonetos Fluorados/toxicidade , Simulação de Acoplamento Molecular , Praguicidas/farmacologia , Praguicidas/toxicidade
4.
J Mol Graph Model ; 97: 107545, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32062583

RESUMO

While the induced-fit of a ligand towards an enzyme is pivotally dictated by intermolecular hydrogen bonds between the small molecule and amino acid residues in the binding site, the role of intramolecular hydrogen bond as contributing interaction for a bioactive conformation is not well understood. This work reports a theoretical conformational analysis of a thymidine kinase enzyme ligand (NMF) that is prone to experience an F⋯HO intramolecular hydrogen bond, inside and outside the biological binding site. This interaction stabilizes the most favorable conformations of NMF in the gas phase and, although it can be disrupted in a biological environment due to intermolecular hydrogen bonds in some cases, these interactions are competitive in other systems. Therefore, an intramolecular hydrogen bond can affect the conformational likeliness most related to the bioactivity. Moreover, isolated conformations governed by this interaction cannot be unequivocally used to generate molecular descriptors in 3D-QSAR (Quantitative Structure-Activity Relationships), since the bioactive conformation may not be determined only by intramolecular interactions.

5.
Neurosci Lett ; 714: 134566, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31698027

RESUMO

Bipolar disorder is a chronic mood disorder characterized by episodes of mania and depression. The aim of this study was to investigate the effects of blackberry extract on behavioral parameters, oxidative stress and inflammatory markers in a ketamine-induced model of mania. Animals were pretreated with extract (200 mg/kg, once a day for 14 days), lithium chloride (45 mg/kg, twice a day for 14 days), or vehicle. Between the 8th and 14th days, the animals received an injection of ketamine (25 mg/kg) or vehicle. On the 15th day, thirty minutes after ketamine administration, the animals' locomotion was assessed using open-field apparatus. After the experiments, the animals were euthanized and cerebral structures were removed for neurochemical analyses. The results showed that ketamine treatment induced hyperlocomotion and oxidative damage in the cerebral cortex, hippocampus and striatum. In contrast, pretreatment with the extract or lithium was able to prevent hyperlocomotion and oxidative damage in the cerebral cortex, hippocampus, and striatum. In addition, IL-6 and IL-10 levels were increased by ketamine, while the extract prevented these effects in the cerebral cortex. Pretreatment with the extract was also effective in decreasing IL-6 and increasing the level of IL-10 in the striatum. In summary, our findings suggest that blackberry consumption could help prevent or reduce manic episodes, since this extract have demonstrated neuroprotective properties as well as antioxidant and anti-inflammatory effects in the ketamine-induced mania model.

6.
Rev. bras. cineantropom. desempenho hum ; 22: e70607, 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1137233

RESUMO

Abstract Intense physical activity can increase oxidative stress and muscle damage in, causing fatigue and injury. Graduated compression stockings (GCS) can decrease these deleterious effects. The aim was to determine the acute effects of GCS on muscle damage and oxidative stress (OS) in garbage collectors. Thirteen garbage collectors, 25.4±5.2 years, participated using GCS or placebo stockings. Blood samples were collected at pre and post a working day and after 16 hours of rest. Markers of OS and muscle damage were evaluated. Two-way ANOVA (two conditions and two moments) was used for the analysis of the outcomes No significant differences were found for creatine kinase, catalase and glutathione peroxidase between the time and groups. There was a significant difference for the total thiol content and superoxide dismutase only in the control group (pre and post, p = 0.004). The use of GCS exerted acute protection against the increase of markers of OS, but did not contribute to attenuate muscle damage.


Resumo Atividade física intensa pode aumentar o estresse oxidativo e danos musculares, causando fadiga e lesões. As meias de compressão graduada (MCG) podem diminuir esses efeitos deletérios. O objetivo foi determinar os efeitos agudos da MCG no dano muscular e estresse oxidativo (EO) em coletores de lixo. Treze coletores de lixo, 25,4 ± 5,2 anos, participaram usando MCG ou placebo. As amostras de sangue foram coletadas antes e após um dia útil e após 16 horas de descanso. Marcadores de EO e dano muscular foram avaliados. ANOVA de duas vias (duas condições e dois momentos) foi usada para á análise dos resultados. Não foram encontradas diferenças significativas para creatina quinase, catalase e glutationa peroxidase entre o tempo e os grupos. Houve uma diferença significativa para o conteúdo total tiólico e superóxido dismutase apenas no grupo controle (pré e pós, p = 0,004). O uso de MCG exerceu proteção aguda contra o aumento de marcadores de EO, mas não contribuiu para atenuar danos musculares

7.
Phys Chem Chem Phys ; 21(34): 18622-18628, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31414084

RESUMO

Spin-spin coupling constant (SSCC) data may be useful in providing information on the stereochemistry and intramolecular interactions in molecules. One-bond C-H and C-F SSCCs (1JCH and 1JCF) are amongst the most important NMR parameters used to study the structure of alicyclic six-membered rings, because the Perlin effect, defined as 1JCHeq > 1JCHax, and the fluorine Perlin-like effect, defined as |1JCFeq| > |1JCFax|, are in wide currency to probe the conformations of these compounds. The origin of these effects has been usually attributed either to dipolar interactions or hyperconjugation, while the induced current density (ICD) has been recently correlated to the magnetic shielding tensors in some six-membered ring compounds, and then used to explain the Perlin effect. Accordingly, this work reports an analysis of the ICD as a descriptor of 1JCH and 1JCF in a series of six-membered rings to find out the role of the ICD in the conventional and fluorine Perlin effect. The atoms in molecules (AIM) magnetic responses obtained from density functional theory (DFT) calculations for the studied compounds did not show any relationship of the first-order electronic current density (ΔJ(1)) with the calculated Δ1JCHax-eq and Δ1JCFax-eq values. Consequently, the title effects cannot be precisely explained by ICD. Nevertheless, an interesting relationship between ΔJ(1) and Δdelocalization involving σCH* orbitals is observed.

8.
Mol Inform ; 38(6): e1800167, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30945816

RESUMO

The structure of bioactive compounds inside their biological target is mainly dictated by the intermolecular interactions present in the binding side, whereas intramolecular interactions are responsible for the structure of an isolated molecule. Accordingly, this work reports the relative significance of these interactions for the bioactive conformation of the N-protonated epinephrine. The crystallized structure of epinephrine has a gauche orientation of the O-C-C-N torsion angle. Conformational analysis in the gas phase and implicit water was performed to investigate the main intramolecular forces favoring this conformational preference, which was primarily attributed to the electrostatic interaction between hydroxyl and ammonium groups. However, when the conformers were docked into the active site, intramolecular interactions were surpassed by intermolecular hydrogen bonds with neighboring amino acid residues. Nonetheless, structural modifications aiming at strengthening intramolecular interactions could be used to modulate a bioactive conformation, thereby assisting in the structure-based design of new chemical entities.


Assuntos
Epinefrina/química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , Eletricidade Estática
9.
Beilstein J Org Chem ; 15: 506-512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873234

RESUMO

The active species of the Ishikawa´s reagent [N,N-diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine] is a fluorinating hexafluoropropylamine used to convert alcohols into alkyl fluorides. On the other hand, it is also an example of model compound useful to probe conformational preferences using spectroscopic information from diastereotopic fluorines. Moreover, the possibility of experiencing both the generalized anomeric and gauche effects makes the Ishikawa´s reagent an ideal choice to study the governing stereoelectronic interactions of the conformational equilibrium of organofluorine compounds. The conformational equilibrium of the Ishikawa´s reagent was analyzed using NMR 3 J H,F coupling constant data in different solvents, since the orientation of the diastereotopic fluorines relative to H-2 and F-2 changes with the medium. In nonpolar cyclohexane solvent, the preferred conformation experiences a weaker steric and electrostatic repulsion. The conformational behavior changes in the more polar pyridine solution, where the double fluorine gauche effect takes place, since F-2 is preferably gauche to both diastereotopic fluorines. An analysis of the rotation around the N-C(F2) bond indicates the manifestation of anomeric interactions (n N → σ*C-F), which can be demonstrated by means of 19F chemical shifts. The results were rationalized with the aid of theoretical calculations and natural bond orbital (NBO) analysis, allowing for the evaluation of competing steric, electrostatic and hyperconjugative interactions.

10.
Magn Reson Chem ; 57(7): 373-379, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30776853

RESUMO

The Perlin effect and its analog for fluorinated compounds (the fluorine Perlin-like effect) manifest on one-bond C─H (C─F for the fluorine Perlin-like effect) spin-spin coupling constants (SSCCs) in six-membered rings. These effects can be useful to probe the stereochemistry (axial or equatorial) of the C─H and C─F bonds, respectively. The origin of these effects has been debatable in the literature as being due to hyperconjugative interactions, dipolar effects, and induced current density. Accordingly, a variety of model compounds has been used to probe such effects since the cyclohexanone carbonyl group and the endocyclic heteroatom lone pairs play different roles on the above-mentioned effects. Thus, the 1 JC─F SSCC in fluorinated lactams and lactones were theoretically studied to gain further insight on the nature of the fluorine Perlin-like effect. In addition, because the intramolecular α-effect has recently gained attention for its importance in the reactivity and stereoelectronic interactions in peroxide compounds, some fluorinated 1,2-dioxanes and 1,2-dithianes were studied to evaluate the role of the α-effect on the behavior of 1 JC─F SSCCs. Differently from fluorinated ketones and ethers, the fluorine Perlin-like effect in the amides and esters cannot be explained by hyperconjugative or dipolar interactions alone, because the resonance in these groups affect the 1 JC─F values. The O─O and S─S-containing systems exhibit a strong fluorine Perlin-like effect, but unlike the α-effect, this behavior cannot be explained neither by hyperconjugation nor by dipolar interactions alone; the spatial proximity of the C─F and O─O/S─S bonds is proposed to affect the magnitude of the 1 JC─F SSCC.

11.
Chem Biol Drug Des ; 93(6): 1096-1104, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30411494

RESUMO

Quantitative structure-activity relationship (QSAR) is a molecular modeling technique widely used in the discovery of novel drugs. Currently, there are many approaches for performing such analysis, which are commonly classified from 1D to 6D. 2D and 3D techniques are among the most exploited ones. Multivariate image analysis applied to QSAR (MIA-QSAR) is an example of 2D methodology that has presented a satisfactory performance in the generation of effective prediction models for biological/physicochemical properties. However, once this is a 2D method, conformational information is not explicitly considered, despite the well-known role of such type of information in explaining the biochemical behavior. Thus, the importance of conformation is undeniable, but the requirement of this information for QSAR analysis still needs to be studied. Therefore, this work aimed to provide a method for encoding 3D information into MIA-QSAR descriptors and analyze the consequences of this inclusion on this methodology. The strategy consisted in fully optimizing the molecular geometries of anti-HCV compounds and three-dimensionally align them before performing the MIA-QSAR procedure. As a result, it was possible to verify that this type of information does not improve the MIA-QSAR modeling performance; instead, the traditional procedure consisting of maximally congruent substructures generated a more reliable prediction model.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Antivirais/química , Estrutura Molecular
12.
Magn Reson Chem ; 56(9): 810-816, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29667226

RESUMO

Earlier studies with 2-bromocyclohexanone demonstrated a measurable long-range coupling constant (4 JH2,H6 ) for the equatorial conformer, although 4 JH2,H4 and 4 JH4,H6 were not observed; as a consequence, it is inferred that the carbonyl group plays an important role particularly due to hyperconjugative interactions σC2H2 →π*C═O and σC6H6 →π*C═O. In the present study, NBO analysis and coupling constant calculations were performed to cyclohexanone and cyclohexanethione alpha substituted with F, Cl, and Br, aiming to evaluate the halogen effect and acceptor character of the π* orbital on the long-range coupling pathway. The σC2H2 →π*C1═Y and σC6H6 →π*C1═Y (Y═O and S) hyperconjugative interactions for the equatorial conformer indeed contribute for the 4 JH2,H6 transmission mechanism. Surprisingly, the 4 JH2,H6 value is higher for the carbonyl compounds, although the interactions σC2H2 →π*C═Y and σC6H6 →π*C═Y are more efficient for the thiocarbonyl compounds. Accordingly, the Fermi contact (FC) contribution for the thiocarbonyl compounds decays deeper than in ketones, thus reducing more the 4 JH2,H6 values. Moreover, both πC═S →σ*C─X and πC═S →σ*C─H interactions seem to be stronger in thiocarbonyl than in carbonylic compounds. The implicit solvent effect (DMSO and water) on the coupling constant values was negligible when compared with the gas phase. On the other hand, an explicit solvent effect was found and 4 JH2,H6 for the thiocarbonyl compounds appeared to be more sensitive than for the cyclohexanones.

13.
ACS Comb Sci ; 20(2): 75-81, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29297675

RESUMO

We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally diverse chemical compound data sets. Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. These compounds were docked into the aromatase active site, and the 10 most promising compounds were selected for in vitro experimental validation. Of these compounds, 7419 (nonsteroidal) and 89 201 (steroidal) demonstrated satisfactory antiproliferative and aromatase inhibitory activities. The obtained results suggest that the 2D-DFT MIA-QSAR method may be useful in ligand-based virtual screening of new molecular entities of therapeutic utility.


Assuntos
Inibidores da Aromatase/química , Modelos Moleculares , Antineoplásicos/química , Antineoplásicos/farmacologia , Aromatase/metabolismo , Inibidores da Aromatase/metabolismo , Inibidores da Aromatase/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Análise de Fourier , Humanos , Ligantes , Células MCF-7 , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Análise Multivariada , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
14.
ACS Omega ; 3(8): 10250-10254, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459154

RESUMO

The conformational behavior of cyclic monosaccharides has been widely studied over the past years, but there is no general agreement about which effects are in fact responsible for the observed conformational preferences. A recent microwave spectroscopy study determined the conformational equilibrium of d-glucose in the gas phase with a preference for a counterclockwise arrangement of the hydroxyl groups. Nevertheless, the effects that control this orientation are still uncertain because the role of intramolecular hydrogen bonds (IHBs), electrostatic and steric repulsions is not clear. This work reports a density functional theory approach based on the conformational energies of d-glucose and of some derivatives in which the anomeric hydroxyl is replaced with hydrogen (H, small and not prone to participate in proton transfer), fluorine (F, small, electronegative, and as capable as OH of forming hydrogen bonds as a proton acceptor), and chlorine (Cl, big and not anticipated to be involved in effective hydrogen bond formation) to obtain insights into the effects of the substituent at the anomeric carbon on the arrangement of the hydroxyl groups in d-glucose. The nature of the substituents at this position is crucial to determine the orientation of the remaining hydroxyl groups. Natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses, in addition to NMR chemical shift calculations, have been provided to support the conformational energy outcomes. Overall, the results agree with the lack of IHBs forming four- and five-membered rings in d-glucose and emphasize that steric and electrostatic repulsions involving the hydroxyl groups in the clockwise orientation are driving forces of the conformational behavior.

15.
J Org Chem ; 82(23): 12181-12187, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29058903

RESUMO

An earlier study demonstrated that hyperconjugation operates in hydrazides by analyzing the N-H stretching mode in gas phase infrared (IR) spectroscopy, and then observing two very distinct bands corresponding to isolated isomers experiencing or not the nN → σ*N-H electron delocalization. The present work reports a chemical method to obtain insight on the hyperconjugation in hydrazide derivatives from solution IR spectroscopy. The analogous amides did not show a νN-H red-shifted band, as the electron donor orbital in the above hyperconjugative interaction does not exist. In addition, the effect of electron withdrawing groups bonded to a nitrogen atom, namely the trifluoroacetyl and the methanesulfonyl groups, was analyzed on the conformational isomerism and on the ability to induce a stronger hyperconjugation in the resulting compounds.

16.
Beilstein J Org Chem ; 13: 1781-1787, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28904621

RESUMO

2-Haloketones are building blocks that combine physical, chemical and biological features of materials and bioactive compounds, while organic fluorine plays a fundamental role in the design of performance organic molecules. Since these features are dependent on the three-dimensional chemical structure of a molecule, simple structural modifications can affect its conformational stability and, consequently, the corresponding physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the compounds. Spectroscopic parameters (NMR chemical shifts and coupling constants), which can be useful to determine the stereochemistry and the interactions operating in the series of 2-fluorocyclohexanone derivatives, were also calculated.

17.
Carbohydr Res ; 451: 29-35, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-28941406

RESUMO

Conformational effects, including some controversial examples, have been reported in this work for 2-substituted tetrahydropyrans and piperidines, and for the respective protonated compounds [substituent = F, OH, OCH3, NH2, NHCH3 and N(CH3)2]. Hyperconjugation plays a major role in most cases, either due to endo or exo-anomeric interactions, especially when nitrogen is the electron donor to an antiperiplanar σ* orbital. This interaction also seems to contribute for the Perlin and reverse fluorine Perlin-like effects, which are related to the relative magnitude of 1JC,H and 1JC,F coupling constants, respectively, in axial and equatorial conformers. However, the preference for an equatorial conformation appears when a hydrogen or methyl group of the substituent faces the ring, increasing the steric repulsion, even if concomitant with a hyperconjugative interaction in the axial isomer, such as for the well-known 2-aminotetrahydropyran. Unlike some reports in the literature, the gas phase 2-hydroxypiperidine experiences the herein called reverse anomeric effect, although the highly stabilizing nN → σ*C-O interaction in the axial isomer. Overall, steric effects should be taken into account when deciding for the normal or reverse anomeric effects as determinant factors of the stereochemical control of carbohydrate-like molecules.


Assuntos
Piperidinas/química , Piranos/química , Modelos Moleculares , Conformação Molecular , Teoria Quântica , Estereoisomerismo , Termodinâmica
18.
Mol Inform ; 36(12)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28845912

RESUMO

There has been an increasing interest in the study of fluorinated derivatives of gamma-aminobutyric acid (GABA), an acetylcholine (AC) analog. This work reports a theoretical study on the effect of an α-carbonyl fluorination in AC, aiming at understanding the role of a distant fluorine relative to the positively charged nitrogen on the conformational folding of the resulting fluorinated AC. In addition, the chemical and structural changes were evaluated on the basis of ligand-enzyme (acetylcholinesterase) interactions. In an enzyme-free environment, the fluorination yields conformational changes relative to AC due to the appearance of some attractive interactions with fluorine and a weaker steric repulsion between the fluorine substituent and the carboxyl group, rather than to a possible electrostatic interaction F⋅⋅⋅N+ . Moreover, the gauche orientation in the N-C-C-O fragment of AC owing to the electrostatic gauche effect is reinforced after fluorination. For instance, the conformational equilibrium in AC is described by a competition between gauche and anti conformers (accounting for the N-C-C-O dihedral angle) in DMSO, while the population for a gauche conformer in the fluorinated AC is almost 100 % in both gas phase and DMSO. However, this arrangement is disrupted in the biological environment even in the fluorinated derivative (whose bioconformation-like geometry shows a ligand-protein interaction of -84.1 kcal mol-1 against -79.5 kcal mol-1 for the most stable enzyme-free conformation), which shows an anti N-C-C-O orientation, because the enzyme induced-fit takes place. Nevertheless, the most likely bioconformation for the fluorinated AC does not match the bioactive AC backbone nor the most stable enzyme-free conformation, thus revealing the role of fluorination on the bioconformational control of AC.


Assuntos
Acetilcolina/química , Halogenação , Hidrocarbonetos Fluorados/química , Teoria Quântica , Acetilcolina/metabolismo , Hidrocarbonetos Fluorados/síntese química , Conformação Molecular , Método de Monte Carlo
19.
Magn Reson Chem ; 55(12): 1079-1083, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28703432

RESUMO

The 1 JC-F coupling constant can be useful to probe the conformational landscape of organofluorine compounds and the intramolecular interactions governing the stereochemistry of these compounds. Neighboring oxygen electron lone pairs and a carbonyl group relative to a C─F bond affect this coupling constant in an opposite way, and therefore, analysis of the interactions involving these entities simultaneously indicates which effect dominates 1 JC-F . Spin-spin coupling constant calculations for a series of fluorinated tetrahydropyrans, cyclohexanones, and dihydropyran-3-ones indicated that an electrostatic/dipolar interaction between the C─F and C═O bonds is more important than the steric interaction between the C─F bond and the oxygen electron lone pairs. An intuitive consequence of such outcome is that this interaction not only drives the coupling constant but can also be taken into account when aiming at the stereochemical control of functionalized organofluorine compounds.

20.
Ecotoxicol Environ Saf ; 144: 560-563, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28688357

RESUMO

Soil sorption of insecticides employed in agriculture is an important parameter to probe the environmental fate of organic chemicals. Therefore, methods for the prediction of soil sorption of new agrochemical candidates, as well as for the rationalization of the molecular characteristics responsible for a given sorption profile, are extremely beneficial for the environment. A quantitative structure-property relationship method based on chemical structure images as molecular descriptors provided a reliable model for the soil sorption prediction of 24 widely used organophosphorus insecticides. By means of contour maps obtained from the partial least squares regression coefficients and the variable importance in projection scores, key molecular moieties were targeted for possible structural modification, in order to obtain novel and more environmentally friendly insecticide candidates. The image-based descriptors applied encode molecular arrangement, atoms connectivity, groups size, and polarity; consequently, the findings in this work cannot be achieved by a simple relationship with hydrophobicity, usually described by the octanol-water partition coefficient.


Assuntos
Inseticidas/análise , Modelos Teóricos , Compostos Organofosforados/análise , Poluentes do Solo/análise , Solo/química , Adsorção , Interações Hidrofóbicas e Hidrofílicas , Inseticidas/química , Conformação Molecular , Análise Multivariada , Octanóis/química , Compostos Organofosforados/química , Relação Quantitativa Estrutura-Atividade , Poluentes do Solo/química , Água/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...