Structural pharmacology and therapeutic potential of 5-methoxytryptamines.

Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders1-3. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT2A (ref. 4). However, 5-HT1A also plays a part in the behavioural effects of tryptamine hallucinogens5, particularly 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a psychedelic found in the toxin of Colorado River toads6. Although 5-HT1A is a validated therapeutic target7,8, little is known about how psychedelics engage 5-HT1A and which effects are mediated by this receptor. Here we map the molecular underpinnings of 5-MeO-DMT pharmacology through five cryogenic electron microscopy (cryo-EM) structures of 5-HT1A, systematic medicinal chemistry, receptor mutagenesis and mouse behaviour. Structure-activity relationship analyses of 5-methoxytryptamines at both 5-HT1A and 5-HT2A enable the characterization of molecular determinants of 5-HT1A signalling potency, efficacy and selectivity. Moreover, we contrast the structural interactions and in vitro pharmacology of 5-MeO-DMT and analogues to the pan-serotonergic agonist LSD and clinically used 5-HT1A agonists. We show that a 5-HT1A-selective 5-MeO-DMT analogue is devoid of hallucinogenic-like effects while retaining anxiolytic-like and antidepressant-like activity in socially defeated animals. Our studies uncover molecular aspects of 5-HT1A-targeted psychedelics and therapeutics, which may facilitate the future development of new medications for neuropsychiatric disorders.

Cyclopeptide-ß-cyclodextrin/γ-glycerol methoxytrimethoxysilane film for potential vascular tissue engineering scaffolds.

The mortality rate of cardiovascular diseases is the highest among all mortality rates worldwide. Allotransplantation and autotransplantation are limited by rejection reaction and availability. Tissue engineering provides new avenues for the treatment of cardiovascular diseases. However, the current small-diameter (<6 mm) vascular tissue-engineered scaffolds have many challenges, including thrombosis, stenosis, and infection. Small-diameter vascular scaffolds have structural and compositional requirements such as biocompatibility, porosity, and appropriate phase separation. We used liquid-crystal cyclopeptide（CYC）to modify ß-cyclodextrin and mixed it with γ-glycerol methoxytrimethoxysilane (GPTMS) to prepare CYC-ß-cyclodextrin (ßCD)/GPTMS film by sol-gel. The chemical structure of CYC-ßCD was confirmed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The chemical characterization of CYC-ßCD/GPTMS film was performed by differential scanning calorimetry, X-ray diffraction, and small-angle X-ray scattering. The surface morphology and phase separation microstructure of the film were determined by scanning electron microscopy and atomic force microscopy, and the image of polarizing microscopy showed the liquid-crystal structure of the film. Cell culture experiments showed that CYC-ßCD/GPTMS film had good cytocompatibility and induced growth and proliferation of cells. These results indicated the potential applications of CYC-ßCD/GPTMS film in tissue engineering scaffolds.

Structural and Molecular Dynamics Analysis of Plant Serotonin N-Acetyltransferase Reveal an Acid/Base-Assisted Catalysis in Melatonin Biosynthesis.

Serotonin N-acetyltransferase (SNAT) is the key rate-limiting enzyme in melatonin biosynthesis. It mediates melatonin biosynthesis in plants by using serotonin and 5-methoxytryptamine (5-MT), but little is known of its underlying mechanisms. Herein, we present a detailed reaction mechanism of a SNAT from Oryza sativa through combined structural and molecular dynamics (MD) analysis. We report the crystal structures of plant SNAT in the apo and binary/ternary complex forms with acetyl-CoA (AcCoA), serotonin, and 5-MT. OsSNAT exhibits a unique enzymatically active dimeric fold not found in the known structures of arylalkylamine N-acetyltransferase (AANAT) family. The key residues W188, D189, D226, N220, and Y233 located around the active pocket are important in catalysis, confirmed by site-directed mutagenesis. Combined with MD simulations, we hypothesize a novel plausible catalytic mechanism in which D226 and Y233 function as catalytic base and acid during the acetyl-transfer reaction.

Application of hair analysis to document illegal 5-methoxy-N,N-dissopropyltrptamine (5-MeO-DiPT) use.

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT) is a designer hallucinogen that is a synthetic tryptamine derivative. It is highly abused and is involved in criminal activities because of its psychotropic properties. Herein, we presented an UHPLC-MS/MS method allowing for the qualitative and quantitative determination of 5-MeO-DiPT in human hair. The hair was first decontaminated and then cut into pieces. Thirty milligrams of hair samples was pulverized below 4°C in the presence of 0.5mL deionized water containing 0.1% formic acid. After centrifuging twice, 5µL of supernatant was injected into the LC-MS/MS system. A T3 column (100mm×2.1mm, 1.8µm) was used, and mobile phases consisted of 20mmol/L ammonium acetate, 5% acetonitrile and 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). The gradient elution was used at a flow rate of 0.3mL/min. The resulting calibration curve for 5-MeO-DiPT was y=281.50213x+0.00231 (R2=0.992), the limit of detection (LOD) was 0.05pg/mg, and the lower limit of quantification (LLOQ) was 0.1pg/mg. The accuracy was between 92.1% and 105.6%, and the intra- and interday precision, recovery and matrix effect were acceptable. The validated method was successfully used in 106 real cases, and the concentration of 5-MeO-DiPT in hair samples of these suspected users was 0.2-7532.5pg/mg. These cases present data to document illegal 5-MeO-DiPT use.

Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC-MS, LC-MSn , and LC-HR-MS/MS.

Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MSn ), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MSn , and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd.

The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury.

Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS). The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA), which was synthesized from melatonin and α-lipoic acid, against radiation-induced hematopoietic injury. MLA administration significantly enhanced the survival rate of mice after 7.2 Gy total body irradiation. The results showed that MLA not only markedly increased the numbers and clonogenic potential of hematopoietic cells but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, MLA decreased the levels of ROS in hematopoietic cells by inhibiting NOX4 expression. These data demonstrate that MLA prevents radiation-induced hematopoietic syndrome by increasing the number and function of and by inhibiting DNA damage and ROS production in hematopoietic cells. These data suggest MLA is beneficial for the protection of radiation injuries.

Optimization of a nano-enzymatic reactor for on-line tryptic digestion of polypeptide conjugates by capillary electrophoresis.

This work aims at studying the optimization of an on-line capillary electrophoresis (CE)-based tryptic digestion methodology for the analysis of therapeutic polypeptides (PP). With this methodology, a mixture of surrogate peptide fragments and amino acid were produced on-line by trypsin cleavage (enzymatic digestion) and subsequently analyzed using the same capillary. The resulting automation of all steps such as injection, mixing, incubation, separation and detection minimizes the possible errors and saves experimental time. In this paper, we first study the differents parameters influencing PP cleavage inside the capillary (plug length, reactant concentration, incubation time, diffusion and electrophoretic plugs mixing). In a second part, the optimization of the electrophoretic separation conditions of generated hydrolysis products (nature, pH and ionic strength (I) of the background electrolyte (BGE)) is described. Using the optimized conditions, excellent repeatability was obtained in terms of separation (migration times) and proteolysis (number of products from enzymatic hydrolysis and corresponding amounts) demonstrating the robustness of the proposed methodology.

Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines.

RATIONALE: Substances based on the N-(2-methoxybenzyl)phenethylamine template ('NBOMe' derivatives) play an important role in medicinal research but some of these derivatives have also appeared as 'research chemicals' for recreational use which has attracted attention worldwide. A major challenge associated with newly emerging substances includes the lack of analytical data and the ability to correctly identify positional isomers. METHODS: Six N-benzylphenethylamines based on the 2,5-dimethoxy-4-iodophenethylamine structure ('25I') and twelve substituted N-benzyl-5-methoxytryptamines ('5MT') have been prepared and extensively characterized. Techniques used for characterization were gas chromatography/ion trap mass spectrometry in electron and chemical ionization mode, liquid chromatography/diode array detection (DAD), infrared spectroscopy, electrospray high mass accuracy quadrupole time-of-flight tandem mass spectrometry, and triple quadrupole tandem mass spectrometry. RESULTS: The characterization of 18 'NBOMe' compounds provided a comprehensive collection of chromatographic and spectral data. Four groups of three positional isomers, i.e. 25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25I-NB3B, 25I-NB4B and their 5-methoxytryptamine counterparts, were included and assessed for ability to obtain differentiation. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine (CF3, F, CH3, Cl, I, SCH3) were also studied. CONCLUSIONS: The implementation of mass spectral techniques was helpful for the differentiation between isomers, for example, when considering the difference in a number of ion ratios. This was considered beneficial in cases where chromatographic separation was only partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD analysis was also found to be valuable for this particular purpose, which confirmed the integrative value of complementary techniques used in areas related to forensic toxicology.

5-Methoxytryptamine reacts with natural food flavour to produce 6-methoxy tetrahydro-ß-carbolines: in vitro investigation of their antioxidant and cytotoxicity properties.

Various 6-methoxytetrahydro-ß-carboline derivatives, namely BEN (6-methoxy-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ANI (6-methoxy-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ACE (6-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole) and VAN (2-methoxy-4-(6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-l)phenol), were prepared via the Maillard reaction using food flavours and 5-methoxytryptamine in aqueous medium and were investigated for their in vitro antioxidant and cytotoxicity properties. These derivatives were found to exhibit moderate antioxidant properties, based on a combination of DPPH, ABTS and FRAP assays. The results suggested that the Maillard reaction could be used to generate ß-carboline antioxidants. It was beneficial that VAN showed the highest antioxidant activity but the least cytotoxic activities on non-tumourous cell lines of NIH/3T3, CCD18-Co and B98-5 using MTT assay. ACE, ANI and BEN showed mild toxicity at effective antioxidative concentrations derived from DPPH and ABTS assays. Furthermore, they are safer compared to 5-fluorouracil, cisplatin and betulinic acid on NIH/3T3, CCD18-Co and B98-5 cells. In conclusion, the antioxidant and cytotoxicity properties of 6-methoxytetrahydro-ß-carbolines were demonstrated for the first time.

N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues.

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotonin receptors showed that most of the compounds had the highest affinity at the 5-HT2 family receptors. Substitution at the para position of the benzyl group resulted in reduced affinity, whereas substitution in either the ortho or the meta position enhanced affinity. In general, introduction of a large lipophilic group improved affinity, whereas functional activity often followed the opposite trend. Tests of the compounds for functional activity utilized intracellular Ca(2+) mobilization. Function was measured at the human 5-HT2A, 5-HT2B, and 5-HT2C receptors, as well as at the rat 5-HT2A and 5-HT2C receptors. There was no general correlation between affinity and function. Several of the tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM), but most were partial agonists. Tests in the mouse head twitch assay revealed that many of the compounds induced the head twitch and that there was a significant correlation between this behavior and functional potency at the rat 5-HT2A receptor.

The antioxidant behaviour of melatonin and structural analogues during lipid peroxidation depends not only on their functional groups but also on the assay system.

There is no general agreement yet on the antioxidant effect of pineal indoles against lipid peroxidation. Accordingly, the main goal of the present work was to study the antioxidant activity of melatonin (MLT), N-acetylserotonin (NAS), 5-HO-tryptophan (5HO-TRP) and 5-methoxytryptamine (5MTP) in two different lipid systems with high content of polyunsaturated fatty acids (PUFAs): triglycerides (rich in 20:5 n-3, 22:6 n-3) dissolved in chloroform and sonicated liposomes made of retinal lipids (rich in 22:6 n-3). In the triglyceride-chloroform-system the peroxidation reaction was initiated by cumene hydroperoxide (CHP) whereas liposomes were peroxidized with Fe(2+). The techniques employed at the present work were: (1) TBARS production, (2) DPPH assay, (3) determination of conjugated dienes production and (4) analysis of fatty acid profile by GC-MS. Butylated hydroxytoluene (BHT) was employed as a reference because of its well known antioxidant capacity. Our results showed that MLT and 5MTP were unable to protect PUFAs against lipid peroxidation in both systems, whereas NAS and 5HO-TRP were better antioxidants that BHT in the triglyceride-system but ineffective in the liposome-system. We conclude that the antioxidant behaviour of pineal indoles depends not only on their functional groups but also on the assay system and could be explained by the polar paradox theory.

A quantitative method for simultaneous determination of 5-methoxy-N,N-diisopropyltryptamine and its metabolites in urine using liquid chromatography-electrospray ionization-tandem mass spectrometry.

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a designer hallucinogen derived from tryptamine and is reportedly abused and involved in criminal activities. For the detection of 5-MeO-DIPT use, a liquid chromatography-tandem mass spectrometric method for 5-MeO-DIPT and its metabolites, 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N,N-isopropyltryptamine (5-MeO-IPT) was developed and validated in rat urine. The urine samples were pretreated by protein precipitation with acetonitrile and introduced into a BDS HYPERSIL C(18) column (50 × 2.0 mm, 5 µm) for chromatographic separation. Mobile phases consisted of methanol, water, and 1% formic acid, and gradient elution was used at a flow rate of 0.2 mL/min. For the MS detection, multiple-reaction monitoring analysis was adopted. The linear range was 0.01-10 µg/mL, and the lower limit of quantification was 10 ng/mL for all analytes. The intra- and interday accuracies and precisions met the criteria (<15%). The developed method was successfully applied to the drug-treated rat urine.

Preliminary analgesic properties of deltorphin-5-methoxytryptamine chimeric opioid peptides.

To further understand the relationship between melatonin (MT) and deltorphins (Dels) in pain modulation, two chimeric peptides (Del I-5-methoxytryptamine and Del II-5-methoxytryptamine) both containing 5-methoxytryptamine at the carboxyl-terminal of Dels mimicking MT were designed, synthesized and characterized by tail-flick assay in mice. Results showed that intracerebroventricular (i.c.v.) administration of Del I-5-methoxytryptamine (YaFDVVG-X, X is 5-methoxytryptamine, 5, 50 nmol/kg) or Del II-5-methoxytryptamine (YaFEVVG-X, X is 5-methoxytryptamine, 5, 50 nmol/kg) produced stronger analgesia than deltorphins (Del I or Del II alone), and acting even longer and stronger than cocktails containing Del I or Del II (50 nmol/kg) and MT (50 nmol/kg). Naloxone (i.p., 100 nmol/kg) could totally block the analgesic effects induced by the chimeric peptides, while luzindole (specific antagonist of melatonin receptor, i.p., 250 nmol/kg) could only partially inhibit the effects down to that induced by Dels alone. Interestingly, Del I-5-methoxytryptamine and Del II-5-methoxytryptamine act weaker with δ receptor than Dels in vitro but could induce much longer analgesia through co-activating δ opioid receptor and melatonin receptor.

The roles of amino acid residues at positions 216 and 219 in the structural stability and metabolic functions of rat cytochrome P450 2D1 and 2D2.

We examined the effects of the mutual substitution of amino acid residues at positions 216 and 219 between rat CYP2D1 and CYP2D2 on their microsomal contents and enzymatic functions using a yeast cell expression system and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) as a substrate. CYP2D1 has amino acid residues, leucine and valine, at positions of 216 and 219, respectively, whereas CYP2D2 has phenylalanine and aspartic acid at the same positions. In reduced carbon monoxide-difference spectroscopic analysis, the substitution of Asp-219 of CYP2D2 by valine markedly increased a peak at 450 nm and concomitantly decreased a peak at 420 nm, while the replacement of Phe-216 of CYP2D2 with leucine gave no observable change. The double substitution of Phe-216 and Asp-219 by leucine and valine, respectively, yielded a typical CYP spectrum. The substitution of Val-219 of CYP2D1 by aspartic acid decreased the CYP content to one-half, whereas the replacement of Leu-216 with phenylalanine did not have any effect. The double substitution of Leu-216 and Val-219 of CYP2D1 by phenylalanine and aspartic acid, respectively, diminished the CYP content by 90%. CYP2D1 catalyzed both 5-MeO-DIPT N-deisopropylation and O-demethylation at relatively low levels, while CYP2D2 catalyzed 5-MeO-DIPT O-demethylation efficiently. The substitution of the amino acid at position 216 substantially increased 5-MeO-DIPT oxidation activities of the two CYP2D enzymes. The replacement of the amino acid at position 219 increased the 5-MeO-DIPT O- and N-dealkylation activities of CYP2D1, whereas it decreased the 5-MeO-DIPT O-demethylation activity of CYP2D2. These results indicate that amino acid residues at positions 216 and 219 have important roles in the enzymatic functions of rat CYP2D1 and CYP2D2.

Solubilization of 5-methoxy tryptamine molecular probes in CTAB and SDS micelles: a cmc and binding constant study.

To understand the change in environmental conditions when a probe is incorporated in micelles, an absorption and fluorescence spectral study on the solubilization behaviour of 5-methoxy tryptamine (5-MT) and N,N-dimethyl-5-methoxy tryptamine (5-NMT) has been made in CTAB and SDS for their neutral and cationic forms. The blue shift in emission wavelength is accompanied by increase in intensity with increasing surfactant concentration for almost all the cases except for the cationic probe in CTAB surfactant. This exceptional behaviour can be attributed to the quenching of emission intensity caused by Br(-) ions. Spectral correlations with solvent polarity parameters indicate relatively less polar binding sites in CTAB and SDS as compared to water. The binding constant and cmc values have been determined for CTAB and SDS using both the neutral and the cationic probes, which are in good agreement with the literature values. Higher value of binding constant and lower polarity of the binding sites justify 5-NMT as a better binding probe as the two methyl groups make the molecule more hydrophobic and drag it to the interior of both the micelles.

The effect of melatonin and structural analogues on the lipid peroxidation of triglycerides enriched in omega-3 polyunsaturated fatty acids.

The lipid peroxidation of triglycerides enriched in polyunsaturated fatty acids was investigated by photoemission techniques and the TBARS assay. Butylated hydroxytoluene, 5-OH-tryptophan and N-acetylserotonin inhibited light emission and TBARS formation in a concentration dependent manner. However, it was enhanced in the presence of melatonin and 5-methoxytryptamine and was dependent on its concentration. The total relative luminic units were found to be lower in those systems incubated in the presence of butylated hydroxytoluene, N-acetylserotonin or 5-OH-tryptophan; this decreased proportionally to the concentration of the compound tested. The order of inhibition was 5-OH-tryptophan>N-acetylserotonin>butylated hydroxytoluene with the following IC50 values: 0.65, 6.5 and 9.0 mM respectively. The free-radical scavenging activity of the indole derivatives was also analyzed by the DPPH method, and the results indicate that 5-OH-tryptophan, and N-acetylserotonin exhibited a dose-dependent free-radical scavenging ability at all of the tested concentrations. Thus, at 10 microM concentration a decrease of 84.71% and 73.50% of initial DPPH was observed, compared to 51.00% of BHT. Melatonin and 5-methoxytriptamine decreased the initial concentration of DPPH only 1.85% and 5.0%, respectively. The possible formation of N(1)-acetyl-N(2) formyl-5-methoxykynuramine (AFMK) during lipid peroxidation of triglycerides enriched in PUFAs with cumene hydroperoxide in the presence of melatonin was also analyzed.

Effect of CTAB and SDS micelles on the excited state equilibria of some indole probes.

The absorption and fluorescence spectral characteristics of some biologically active indoles have been studied as a function of acidity and basicity (H_/pH/H(o)) in cationic (cetyltrimethylammonium bromide, CTAB), anionic (sodium dodecylsulphate, SDS) and aqueous phases at a given surfactant concentration. The prototropic equilibrium reactions of these probes have been studied in aqueous and micellar phases and apparent excited state acidity constant (pK(a)(*)) values are calculated. The probes show formation of different species on changing pH. Various species present in water, CTAB and SDS have been identified and the equilibrium constants have been determined by Fluorimetric Titration method. The fluorescence spectral data suggest the formation of oxonium ion through the excited state proton transfer reaction in highly acidic media and formation of photoproducts due to the base catalyzed auto-oxidative reaction in basic aqueous solutions. Variations in the apparent pK(a)(*) value have been observed in different media. The change in the apparent pK(a) values depends upon the solubilising power of the micelles, as well as on the location of the protonating site in the molecule. The observation about increase in pK(a)(*) values in SDS and decrease in CTAB compared to pure water for various equilibria is consistent with the pseudophase ion-exchange (PIE) model.

[5-hydroxytryptamine and 5-methoxytryptamine increase tolerance to global cerebral ischemia].

In the global cerebral ischemia, 5-hydroxytryptamine (serotonin, 5-HT) and 5-methoxytryptamine (5-MT) produce a significant neuroprotector effect closely correlated with their hypothermic action. This expands the spectrum of cerebral functions controlled by 5-HT. At the same time, melatonin and 2-iodmelatonin, which are chemically (but not pharmacologically) close to 5-HT and 5-MT, do not exhibit such protective effects. Probably, an important role in the interaction with 5-HT receptors belongs to the NH2 group of the indole ring.

1H- and 13C-NMR, FTIR, UV-VIS, ESI-MS, and PM5 studies as well as emission properties of a new Schiff base of gossypol with 5-methoxytryptamine and a new hydrazone of gossypol with dansylhydrazine.

A new Schiff base of gossypol with 5-methoxytryptamine (GSTR) and a new hydrazone of gossypol with dansylhydrazine (GHDH) have been synthesized and studied by Fourier transform infrared (FTIR), 1H and 13C nuclear magnetic resonance (NMR), ultraviolet-visible (UV-VIS), electrospray ionization-mass spectroscopy (ESI-MS) as well as the parametric method PM5. The spectroscopic methods have provided clear evidence that GSTR exists in chloroform solution as an enamine-enamine tautomer, whereas GHDH is present in chloroform as a N-imine-N-imine tautomer. The fluorescence spectra of both compounds indicate that their quantum yield of fluorescence is increased by one or two orders of magnitude compared to that of pure gossypol. The ESI-MS spectra of the 1:1 mixtures of GSTR or GHDH with formic acid have demonstrated that both compounds exist as protonated monomers in the gas phase, whereas GHDH can also exist in a stable protonated dimeric structure. The structures of the stable tautomers are calculated and visualized using the PM5 semiempirical method. The intra- and intermolecular hydrogen bonds within these structures are discussed.

Solvent effects in the preparation of molecularly imprinted polymers for melatonin using N-propionyl-5-methoxytryptamine as the pseudo template.

To clarify the role of diluents in the preparation of molecularly imprinted polymers utilizing only hydrogen bonding, we investigated the effects of diluents by using different solvents. Melatonin (N-acetyl-5-methoxytryptamine), an amide bond and indole ring-containing hormone was chosen as the target molecule. N-Propionyl-5-methoxytryptamine was used as the pseudo template, methacrylic acid as the functional monomer, and solvents were used as diluents. Interactions between the template, the functional monomer, melatonin, and the solvents, were observed by 1H NMR spectroscopy. The polymers were evaluated by high-performance liquid chromatography. The results suggest the hydrogen bonding-acceptor capacity of the solvent is the most important factor in the preparation of molecularly imprinted polymers for hydrogen bonding-donating molecules. Hydrogen bonding between the template, the functional monomer, and solvent can be estimated from the chemical shifts in 1H NMR spectra of those molecules in the solvent.