RESUMO
All-trans-retinal, incorporated into dodecylammonium propionate, dodecylammonium 3-chloropropionate and dodecylammonium trifluoroacetate reversed micelles in cyclohexane containing different amounts of solubilized water, gave all-trans-N-retinylidene-n-dodecylamine. Formation of all-trans-N-retinylidene-n-dodecylamine was complete within a few minutes when all-trans-retinal was solubilized along with L-lysine in reversed-micellar dodecylammonium propionate in cyclohexane as compared to the several hours required for the comparable reaction to occur in the absence of lysine. In situ formed all-trans-N-retinylidene-n-dodecylamine was not protonated by the acidic moiety (i.e., propionate, 3-chloropropionate or trifluoroacetate anions) of dodecylammonium propionate, dodecylammonium 3-chloropropionate or dodecylammonium trifluoroacetate reversed micelles. Addition of propionic or 3-chloropropionic acid did not cause observable protonation of the reversed-micelle-incorporated all-trans-N-retinylidene-n-dedecylamine. Addition of strong trifluoroacetic acid to reversed micellar solutions of all-trans-N-retinylidene-n-dodecylamine caused protonation as well as hydrolysis to retinal. Retinylidene Schiff bases are protected from protonation by strongly held surfactant-ion pairs which may model proton channels whose function is controlled by protein conformational changes.
Assuntos
Micelas , Retinaldeído/química , Rodopsina/química , Cicloexanos , Cicloexenos , Prótons , Bases de SchiffRESUMO
The hydrogen bonding-protonation equilibrium for retinyl Schiff base/propionic acid or 3-chloropropionic acid systems was examined by Fourier transform infrared spectroscopy in non polar solutions at temperatures ranging from 25 degrees C to about -150 degrees C. The spectra give evidence for the gradual increase in the degree of protonation as temperature is lowered. The bearing of this on applying low temperature spectroscopic results to physiological conditions in rhodopsin research is discussed.
Assuntos
Pigmentos da Retina , Retinoides , Análise de Fourier , Congelamento , Modelos Teóricos , Bases de Schiff , Soluções , Espectrofotometria Infravermelho/métodosRESUMO
Spectroscopic studies on sodium di(2-ethylhexyl)-sulfosuccinate (AOT) inverted micelles, films of AOT and L-alpha-lysolecithin and on dihexadecyl phosphate vesicles show that histamine and gamma-aminobutyric acid (GABA) act differently on these membrane models. Histamine increases the permeability of the membrane to ions through interactions with its polar sites. GABA, on the other hand, prefers self-association to association with the membrane. If these two neurotransmitters are applied jointly, the result is a decrease in the permeating effect of histamine. Possible mechanisms for these processes are discussed.
Assuntos
Histamina , Membranas Artificiais , Ácido gama-Aminobutírico , Ácido Dioctil Sulfossuccínico , Ligação de Hidrogênio , Lisofosfatidilcolinas , Micelas , Modelos Biológicos , Organofosfatos , Permeabilidade , TensoativosRESUMO
A simple spectroscopic method for the evaluation of the effect that perturbers may have on a membrane model is described. The model was made from dihexadecyl phosphate (DHP) bilayers. The perturbers used were unconventional anesthetics (n-alcohols C1-C8; n-hexane and n-pentane) and conventional anesthetics (chloroform, methoxyflurane, halothane and enflurane). The results show a correlation between vesicle permeation by anesthetics and their clinical potency. Two modes of perturbation by which the anesthetics may induce vesicle permeation are proposed.
Assuntos
Anestésicos , Organofosfatos , Compostos Organofosforados , Álcoois , Modelos Biológicos , Permeabilidade , Relação Estrutura-AtividadeRESUMO
Fourier transform infrared spectroscopic studies are reported on gramicidin ion-channels in phospholipid bilayers and the effects on the spectra of the anesthetics and related compounds (methoxyflurane, halothane, chloroform, carbon tetrachloride, n-pentane and n-decane) have been determined. The addition of anesthetics containing the 'acidic hydrogen' caused unique changes particularly on the amide I bands at 1639 cm-1 and 1670 cm-1. The 1639 cm-1 band became more intense while the intensity near 1670 cm-1 decreased dramatically. These effects were not observed with carbon tetrachloride, n-pentane and n-decane. The 1670 cm-1 band is interpreted as arising from the carbonyls involved in the head-to-head hydrogen-bonded dimerization where the relationship between chains is analogous to that of the antiparallel beta-pleated sheet structure and the anesthetics with 'acidic hydrogens' are considered to disrupt the hydrogen-bonded dimerization by competitive hydrogen bonding to the carbonyls at the head-to-head junction. As the dimer-monomer equilibrium is the 'on-off' mechanism for gramicidin ion-channel conductance, the results are considered in terms of the mechanism of action of anesthetics and are taken to suggest, for certain anesthetics, a hydrogen-bonding role to protein ion-channel components.
Assuntos
Anestesia , Gramicidina , Canais Iônicos/fisiologia , Modelos Biológicos , Espectrofotometria Infravermelho/métodos , Relação Estrutura-AtividadeRESUMO
It is shown that a striking parallelism exists between the anesthetic potency of general halocarbon anesthetics and their influence on the hydrogen bond association constants in N-H...O=C type hydrogen bonds, important for shaping the ion channels. It is further shown that the effect of potent anesthetics (which contain an acidic hydrogen) on the free/associated ratio in such hydrogen bonds is still significant at clinical anesthetic concentrations. It is argued that the results are in keeping with a pluralistic theory of anesthesia based on both hydrophobic and polar interactions.
Assuntos
Acetamidas , Anestésicos , Tetracloreto de Carbono , Ligação de Hidrogênio , Matemática , Modelos Biológicos , Relação Estrutura-AtividadeRESUMO
Perturbation of the hydrogen bonds in the adenine ... thymine base pair by Na+, Mg2+, Ca2+ and NH4+ cations has been investigated by means of ab initio SCF calculations with the STO-3G basis set. The geometry of adenine...thymine, as well as those of the perturbed pairs were optimized. Approach of any cation to thymine at O6 leads to destabilization of the adenine...thymine pair; divalent cations (Mg2+, Ca2+) have a profound effect on the structure of the base pair. The approach of a cation to other available sites (thymine: O2, adenine N1 and N3) leads, on the other hand, to stabilization of the base pair. If a water molecule is placed between the cation and the base pair, the structure and stability of the base pair are changed only negligibly.
Assuntos
Adenina , Cálcio/farmacologia , Magnésio/farmacologia , Compostos de Amônio Quaternário/farmacologia , Sódio/farmacologia , Timina , Composição de Bases , Cátions , Ligação de Hidrogênio , Estrutura Molecular , TermodinâmicaRESUMO
Approximate hydrogen bond association constants were determined for base pairs formed by an adenine derivative and a number of unusual pyrimidine bases. A series is found in which the H-bond strength in the base-pairs varies. In certain cases the H-bond equilibrium constant is larger than in the adenine-thymine pair. Inosine derivatives seem to have a non-negligible chance of replacing guanosine in the guanosine-cytosine pair. Infrared, near-infrared (overtone) and NMR spectra were used to determine the equilibrium constants.
Assuntos
Nucleotídeos , Composição de Bases , Ligação de Hidrogênio , Estrutura Molecular , Análise EspectralRESUMO
It is shown, by quantum chemical calculations, that an Na+ located in the neighborhood of the adenine thymine base-pair can dissociate the hydrogen bonds in it. However, a water molecule placed between Na+ and the base-pair would provide perfect protection for the hydrogen bonds. The suggestion is put forward that a hydrophobic carcinogen (for example) could perturb sufficiently the water structure around DNA to allow Na+ to penetrate to molecular distance from the base-pair. This could result in the 'breaking' of hydrogen bonds and, eventually, irregular cell division.
Assuntos
Adenina , Composição de Bases , Conformação de Ácido Nucleico , Sódio , Timina , Ligação de Hidrogênio , Modelos Genéticos , Teoria Quântica , TermodinâmicaRESUMO
Ab initio self-consistent field calculations with 4-31G and STO-3G basis sets show that Na+ are able to damage the H bonds in the formamidine . formamide complex, modeling the adenine . thymine base pair (both H bonds in the complex investigated are the same as in adenine . thymine). If a water molecule is placed between the complex and Na+, the H bonds of the model are fully protected. Covalent as well as noncovalent binding of polycyclic aromatic hydrocarbons to nucleic acids should decrease the local concentration of water as a result of the insertion of the hydrophobic hydrocarbon into the DNA and thereby increase the exposure of the DNA H bonds to Na+ attack. Thus, Na+ reaching the base pair could provoke or interfere with cell division.
Assuntos
Adenina , Sódio/farmacologia , Timina , DNA , Ligação de Hidrogênio , Conformação de Ácido Nucleico/efeitos dos fármacos , TermodinâmicaRESUMO
Recent views on the photochemistry of (vertebrate) vision are examined. Problems related to the structure of the proton bridge at the Schiff base chromophore are considered, in particular the possible shapes of the section of the potential surface governing the motion of the proton in the bridge. This leads to the question as to whether proton translocation occurs in the initial step of visual transduction and if it precedes or follows cis-trans isomerisation. The related controversy could be solved through the assumption of the presence of water molecules that stabilize the ions in the proton bridge. The causes of the instability of bathorhodopsin are discussed and the importance of additional perturbations by polar groups is stressed.
Assuntos
Prótons , Pigmentos da Retina , Animais , Ligação de Hidrogênio , Isomerismo , Conformação Molecular , Fotoquímica , Rodopsina/análogos & derivados , Análise Espectral Raman , Termodinâmica , Visão Ocular/fisiologia , ÁguaAssuntos
Anestesia Geral , Anestésicos , Anestésicos/antagonistas & inibidores , Anestésicos/classificação , Permeabilidade da Membrana Celular , Fenômenos Químicos , Química , Hidrocarbonetos Halogenados , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Cloreto de Metileno , Biologia Molecular , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
A unified view of the photochemical part of the visual process is presented. It is proposed that both conformational changes and changes in intermolecular interactions in the sequence that leads from rhodopsin through batho-lumi- and meta-I to meta-II- rhodopsin have to be considered in order to elucidate the mechanism of the visual process. The main intermolocular associations are assumed to be the hydrogen bond involving the nitrogen atom of the Schiff base and the interaction between a negative group and the beta-ionone ring. The two together can be used to explain the absorption wavelength of rhodopsin without actual protonation. The main line of thought is as follows: when light is absorbed the basicity of the Schiff base increases significantly. This triggers proton transfer in the H-bond. At the same time cis-trans isomerization begins but it only reaches the coplanar all-trans stage at metarhodopsin-II. Lumi-, meta-I and meta-II are way stations in the stepwise isomerization whereby the energy of the photon is used together with thermal energy. Batho- is probably still close to 11-cis which then becomes successively strained 13-cis and 15-cis. In vertebrate rhodopsins at the meta-II stage both the H-bond and the beta-ionone interaction are severed and meta-II becomes exposed to attack by water molecules. The importance of syn-anti isomerization on the C=N bond is emphasized. The irreversibility necessary for the production of a signal requires that the proton does not return to its original donor. The possible identity of the donor is discussed: it might be an amino acid or the polar part of a lipid. Relevant observations made on bacteriorhodopsin, squid rhodopsin and chicken iodopsin are discussed.