Vibrational spectroscopic approach to the study of acetylcholine and related compounds

The present review reports the coordinated application of three spectroscopic methods (Raman, infrared(IR) and inelastic electron tunneling spectroscopy (IETS)) in the study of the conformation of Ach and some analogues (beta-MeAch, Mu and Nic) in solid state, aqueous solution and in interaction with a surface. Useful correlated information is obtained by Raman and IR spectroscopies on the conformational possibilities of these molecules in transition from solid state to aqueous solution. With this information in hand as well as on the basis of Raman and IR study of the nonenzymatic hydrolysis of Ach, the first detailed experimental investigation of the interaction of Ach and beta-MeAch adsorbed on a surface (A1203) is realised by the IETS method. The results are used to discuss an interaction analogous to that of Ach with receptor and another one analogous to that of Ach and AchE.     

Development of near-infrared firefly luciferin analogue reacted with wild-type and mutant luciferases

Interestingly, only the D-form of firefly luciferin produces light by luciferin–luciferase (L–L) reaction. Certain firefly luciferin analogues with modified structures maintain bioluminescence (BL) activity; however, all L-form luciferin analogues show no BL activity. To this date, our group has developed luciferin analogues with moderate BL activity that produce light of various wavelengths. For in vivo bioluminescence imaging, one of the important factors for detection sensitivity is tissue permeability of the number of photons emitted by L–L reaction, and the wavelengths of light in the near-infrared (NIR) range (700–900 nm) are most appropriate for the purpose. Some NIR luciferin analogues by us had performance for in vivo experiments to make it possible to detect photons from deep target tissues in mice with high sensitivity, whereas only a few of them can produce NIR light by the L–L reactions with wild-type luciferase and/or mutant luciferase. Based on the structure–activity relationships, we designed and synthesized here a luciferin analogue with the 5-allyl-6-dimethylamino-2-naphthylethenyl moiety. This analogue exhibited NIR BL emissions with wild-type luciferase (λ_max = 705 nm) and mutant luciferase AlaLuc (λ_max = 655 nm).     

Ultrastructure of the larval firefly light organ as related to control of light emission

The firefly larva has a pair of light organs consisting of a layer of interdigitating, light emitting cells, covered dorsally with a layer of opaque, white cells. Each light organ is ventilated by one large and several smaller tracheal branches and is innervated by a branch of the segmental nerve containing two axons. These axons branch profusely in the photocyte layer so that several nerve profiles are seen around any photocyte. Nerve terminals contain large dense-core vesicles and small light-core vesicles. Clusters of light-core vesicles surrounding irregularly shaped membrane densifications, presumably the synapses between nerve and photocyte, are common in nerve terminals. Light emitting cells in insects characteristically contain photocyte vesicles. In the larva there are both full and empty photocyte vesicles; the full vesicles contain a matrix with tubular membrane invaginations in contrast to the empty vesicles which contain amorphous membrane invaginations.     

Theoretical insights into the effect of pH values on oxidation processes in the emission of firefly luciferin in aqueous solution

To elucidate the emission process of firefly d ‐luciferin oxidation across the pH range of 7–9, we identified the emission process by comparison of the potential and free‐energy profiles for the formation of the firefly substrate and emitter, including intermediate molecules such as d ‐luciferyl adenylate, 4‐membered dioxetanone, and their deprotonated chemical species. From these relative free energies, it is observed that the oxidation pathway changes from d ‐luciferin → deprotonated d ‐luciferyl adenylate → deprotonated 4‐membered dioxetanone → oxyluciferin to deprotonated d ‐luciferin → deprotonated d ‐luciferyl adenylate → deprotonated 4‐membered dioxetanone → oxyluciferin with increasing pH value. This indicates that deprotonation on 6′OH occurs during the formation of dioxetanone at pH 7–8, whereas luciferin in the reactant has a 6′OH‐deprotonated form at pH 9.     

Antimicrobial properties of substituted salicylaldehydes and related compounds

A systematic survey of the antimicrobial properties of substituted salicylaldehydes and some related aromatic aldehydes is reported. A total of 23 different compounds, each at four different concentrations, were studied using a panel of seven microbes (Aspergillus niger, Bacillus cereus, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Saccharomyces cerevisiae and Staphylococcus epidermidis) and employing the paper disc agar diffusion method. Several aldehydes, most notably halogenated, nitro-substituted and hydroxylated salicylaldehydes, displayed highly potent activity against the microbes studied, giving inhibitory zones up to 49 mm in diameter (paper disc diameter 6 mm), while unsubstituted benzaldehyde and salicylaldehyde had minimal activity. Further, 4,6-dimethoxysalicylaldehyde had considerable activity against C albicans and slight activity against S. cerevisiae, while displaying minimal activity against bacteria. Also two aromatic dialdehydes had interesting activity. In general, P. aeruginosa was the least sensitive microbe, a result that is in line with observations from a large screening project, in which this microbe was the one against which the least number of active substances was found. Interestingly, the structure-activity relationships of the aldehydes studied were clearly different for different microbes. Many of the aldehydes tested had such high antimicrobial activity that they are noteworthy candidates for practical applications as well as interesting lead compounds for the development of novel antimicrobial drugs and disinfectants. The structure-activity relationships are discussed in detail. For high activity, substituents are required in benzaldehyde as well as in its 2-hydroxy derivative salicylaldehyde. One hydroxy group alone (at the 2-position) is not enough, but further hydroxylation may produce high activity. The effects of substituents are in some cases dramatic. Halogenation, hydroxylation and nitro substitution may produce highly active compounds, but the effects are not easily predicted nor can they be extrapolated from one microbe to another.     

Anti-atherosclerotic and anti-diabetic properties of probucol and related compounds

Probucol is a diphenolic compound with anti-oxidant and anti-inflammatory properties that reduces atherosclerosis and restenosis. Unfortunately, adverse effects on blood lipoproteins and cardiac electrophysiology have curtailed its use as a drug. Compounds related to probucol that have improved efficacy without the adverse effects offer promise as novel therapies of cardiovascular disease. Recent results suggest that these compounds may be used for the prevention of type 2 diabetes, a disease that is increasing in prevalence and importance world-wide. In this review, the molecular mechanisms underlying the beneficial activities of probucol and related compounds are described.     

Anti-atherosclerotic and anti-diabetic properties of probucol and related compounds

Abstract

Probucol is a diphenolic compound with anti-oxidant and anti-inflammatory properties that reduces atherosclerosis and restenosis. Unfortunately, adverse effects on blood lipoproteins and cardiac electrophysiology have curtailed its use as a drug. Compounds related to probucol that have improved efficacy without the adverse effects offer promise as novel therapies of cardiovascular disease. Recent results suggest that these compounds may be used for the prevention of type 2 diabetes, a disease that is increasing in prevalence and importance world-wide. In this review, the molecular mechanisms underlying the beneficial activities of probucol and related compounds are described.