Purine Ring Research Articles

Essential Structural Profile of Novel Adenosine Derivatives as Antiplatelet Aggregation Inhibitors based on 3D-QSAR Analysis

Aims: In this research, 3D-QSAR evaluation on a set of fresh purinoid compounds that we produced was conducted. This analysis aims to illustrate the correlation between the structure of purine and its ability to prevent platelet aggregation. Our findings could pave the way to discovering novel antithrombotic medications. Background: The incidence of cardiovascular disease triggered by the clumping of platelets poses a significant danger to human health. Purine derivatives are important molecules with antiplatelet aggregation activity. Objective: The objectives of this research are to establish the correlation between the structure of purine and its ability to prevent platelet aggregation. Such a correlation could aid in the development of innovative antithrombotic medications. Methods: In this study, 3D-QSAR investigation on a collection of 75 new purine derivatives, which we synthesized, was conducted, utilizing Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Results: Significant correlation coefficients (CoMFA, q2= 0.843, r2= 0.930, F value= 266.755, SEE= 0.165; CoMSIA, q2= 0.869, r2= 0.918, F value= 222.571, SEE= 0.179) were obtained, and assessed the model's predictive capabilities by validating it with the test set. Conclusion: Our findings indicate that the introduction of an appropriately sized structure at position 2 of the compound yields significant benefits. Conversely, the attachment of an excessively large group is detrimental. Direct attachment of a bulky substituent at C-6 of the compound is not feasible, and its activity increases when the structure with low electron cloud density is added. Moreover, the presence of a voluminous functional group at the 5' position of the compound is advantageous, and its activity will be further increased by the presence of hydrogen bond receptors in this region. These discoveries furnish significant comprehension for the formation of innovative structures with heightened efficacy.

Multicomponent Synthesis of C(8)-Substituted Purine Building Blocks of Peptide Nucleic Acids from Prebiotic Compounds.

We have explored the reaction of a three-components mixture of aminomalononitrile, urea and α-amino acid methyl esters for the multicomponent synthesis substituted purines resembling PNA's building blocks. 2,6-diamino-purines, 6-amino-3,9-dihydro-2H-purin-2-one (iso-guanines), and 3,9-dihydro-6H-purin-6-one derivatives, selectively decorated at C(8)-position of the purine ring with different amino acid residues, were obtained from acceptable to good yields. The regio-selectivity of the transformation was controlled by the use of urea in the ternary mixture and by the annulation agent involved in the ring-closure of amino-imidazole carbonitrile intermediates. Solvent free conditions, microwave irradiation and simple one-carbon containing reagents further satisfied the major requirement of atom economy and sustainable chemistry. Due to the prebiotic nature of the three-components mixture and of annulation agents, it also embodies the possibility for the synthesis of novel PNAs bearing purine nucleobases decorated at C(8)-position of the imidazole ring as alternative RNA analogues in molecular evolution.

Microbial Uricase and its Unique Potential Applications

Abstract The uricase enzyme yields allantoin, hydrogen peroxide, and carbon dioxide by catalyzing the oxidative opening of the purine ring in the urate pathway. This enzyme is important for biochemical diagnosis and reduces toxic urate accumulation during various diseases (hyperuricemia, gout, and bedwetting). Direct urate oxidase injection is recommended in renal complications-associated gout and to prevent chemotherapy-linked hyperuricemia disorders. Thus, uricase is a promising enzyme with diverse applications in medicine. Microbial production of uricase is featured by high growth rates, cost-effective bioprocessing, and easy optimization of the medium. Microbes produce the enzyme extracellular or intracellular. Extracellular uricase is preferred for biotechnological applications as it minimizes time, effort, and purification processes. This review provides insights into uricase-producing microbes, bacterial uric acid degradation pathways, degrading enzymes, and uricase-encoding genes. Furthermore, aspects influencing the microorganisms’ production of the uricase enzyme, its activity, and its purification procedure are also emphasized. Cell disruption is mandatory for intercellular uricase production, which elevates production costs. Therefore, extracellular uricase-producing microbial strains should be investigated, and production factors should be optimized. Future techniques for obtaining extracellular enzymes should feature reduced time and effort, as well as a simple purification methodology. Furthermore, uricase gene-carrying recombinant probiotic microorganisms could become an effective tool for gout treatment.

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells

Monocyte-derived dendritic cells (MDDCs) are key players in the defense against fungal infection because of their outstanding capacity for non-opsonic phagocytosis and phenotypic plasticity. Accordingly, MDDCs rewire metabolism to meet the energetic demands for microbial killing and biomass synthesis required to restore homeostasis. It has been commonplace considering the metabolic reprogramming a mimicry of the Warburg effect observed in tumor cells. However, this may be an oversimplification since the offshoots of glycolysis and the tricarboxylic acid (TCA) cycle are connected in central carbon metabolism. Zymosan, the external wall of Saccharomyces cerevisiae, contains β-glucan and α-mannan chains that engage the C-type lectin receptors dectin-1/2 and Toll-like receptors. This makes it an optimal fungal surrogate for experimental research. Using real-time bioenergetic assays and [U–13C]glucose labeling, central hubs connected to cytokine expression were identified. The pentose phosphate pathway (PPP) exhibited a more relevant capacity to yield ribose-5-phosphate than reducing equivalents of NADPH, as judged from the high levels of isotopologues showing 13C-labeling in the ribose moiety and the limited contribution of the oxidative arm of the PPP to the production of ROS by NADPH oxidases (NOX). The finding of 13C-label in the purine ring and in glutathione unveiled the contribution of serine-derived glycine to purine ring and glutathione synthesis. Serine synthesis also supported the TCA cycle. Zymosan exhausted NAD+ and ATP, consistent with intracellular consumption and/or extracellular export. Poly-ADP-ribosylated proteins detected in the nuclear fractions of MDDCs did not show major changes upon zymosan stimulation, which suggests its dependence on constitutive Fe(II)/2-oxoglutarate-dependent demethylation of 5-methylcytosine by TET translocases and/or demethylation of histone H3 lysine 27 by JMJD demethylases rather than on NOX activities. These results disclose a unique pattern of central carbon metabolism following fungal challenge, characterized by the leverage of glycolysis offshoots and an extensive recycling of NAD+ and poly(ADP-ribose).

Molecular docking approach for the design and synthesis of new pyrazolopyrimidine analogs of roscovitine as potential CDK2 inhibitors endowed with pronounced anticancer activity

Cyclin-dependent kinase 2 (CDK2) is a vital protein for controlling cell cycle progression that is critically associated with various malignancies and its inhibition could offer a convenient therapeutic approach in designing anticancer remedies. Consequently, this study aimed to design and synthesize new CDK2 inhibitors featuring roscovitine as a template model. The purine ring of roscovitine was bioisosterically replaced with the pyrazolo[3,4-d]pyrimidine scaffold, in addition to some modifications in the side chains. A preliminary molecular docking study for the target chemotypes in the CDK2 binding domain revealed their ability to accomplish similar binding patterns and interactions to that of the lead compound roscovitine. Afterwards, synthesis of the new derivatives was accomplished. Then, the initial anticancer screening at a single dose by the NCI revealed that compounds 7a, 9c, 11c, 17a and 17b achieved the highest GI% values reaching up to 150 % indicating their remarkable activity. These derivatives were subsequently selected to undertake five-dose testing, where compounds 7a, 9c, 11c and 17a unveiled the most pronounced activity against almost the full panel with GI50 ranges; 1.41–28.2, 0.116–2.39, 0.578–60.6 and 1.75–42.4 µM, respectively and full panel GI50 (MG-MID); 8.24, 0.6, 2.46 and 6.84 µM, respectively. CDK2 inhibition assay presented compounds 7a and 9c as the most potent inhibitors with IC50 values of 0.262 and 0.281 µM, respectively which are nearly 2.4 folds higher than the reference ligand roscovitine (IC50 = 0.641 µM). Besides, flow cytometric analysis on the most susceptible and safe cell lines depicted that 7a caused cell cycle arrest at G1/S phase in renal cancer cell line (RXF393) while 9c led to cell growth arrest at S phase in breast cancer cell line (T-47D) along with pronounced apoptotic induction in the mentioned cell lines. These findings afforded new anticancer pyrazolo[3,4-d]pyrimidine, roscovitine analogs, acting via CDK2 inhibition.

Adenine Methylation Enhances the Conformational Flexibility of an RNA Hairpin Tetraloop.

The N6-methyladenosine modification is one of the most abundant post-transcriptional modifications in ribonucleic acid (RNA) molecules. Using molecular dynamics simulations and alchemical free-energy calculations, we studied the structural and energetic implications of incorporating this modification in an adenine mononucleotide and an RNA hairpin structure. At the mononucleotide level, we found that the syn configuration is more favorable than the anti configuration by 2.05 ± 0.15 kcal/mol. The unfavorable effect of methylation was due to the steric overlap between the methyl group and a nitrogen atom in the purine ring. We then probed the effect of methylation in an RNA hairpin structure containing an AUCG tetraloop, which is recognized by a "reader" protein (YTHDC1) to promote transcriptional silencing of long noncoding RNAs. While methylation had no significant conformational effect on the hairpin stem, the methylated tetraloop showed enhanced conformational flexibility compared to the unmethylated tetraloop. The increased flexibility was associated with the outward flipping of two bases (A6 and U7) which formed stacking interactions with each other and with the C8 and G9 bases in the tetraloop, leading to a conformation similar to that in the RNA/reader protein complex. Therefore, methylation-induced conformational flexibility likely facilitates RNA recognition by the reader protein.

Discovery of 2,9-diaryl-6-carbamoylpurines as a novel class of antitubercular agents

A series of novel 9-alkyl/aryl-2-aryl-6-carbamoylpurines were synthesized, and their activity against Mycobacterium tuberculosis strain H37Rv was assessed. The SAR analysis on the first set of derivatives, with an alkyl or aryl unit at N-9 and a phenolic unit at C-2, showed that the activity depends on the purine ring substituents at N-9 and C-2. A phenyl group at N-9 combined with a 3-hydroxyphenyl or 4-hydroxyphenyl at C-2 improve the activity. The most active compound of this set has a phenyl group at N-9 and a 4-hydroxyphenyl group at C-2, displaying an IC90 = 1.2 μg/mL and a selectivity index higher than 25.5. This compound served as a Hit to design the second set of derivatives. A phenyl group at N-9 was maintained, and the group at C-2 was diversified. The SAR analysis showed that the aryl unit at C-2 must have an oxygen or nitrogen atom bonded in the para position. A proton, a small alkyl or a substituted aryl group may also be bonded to the oxygen. The compound with the 4-methoxyphenyl group at C-2, 1Bd, exhibits the highest activity with an IC90 < 0.19 μg/mL. This compound is highly potent against M. tuberculosis strain H37Rv and non-toxic for VERO mammalian cells with an SI > 153.8. Compound 1Bd was also non-cytotoxic against primary macrophage cultures at IC90, 2xIC90, and 10xIC90 and significantly reduced the bacterial load in M. tuberculosis-infected macrophages at the same concentrations. Compound 1Bd showed a favorable pharmacokinetic profile when administered orally, with major lung and liver accumulation. In vivo antimycobacterial efficacy of 1Bd was tested at 25 mg/kg. At the tested regimen, a decrease in bacterial burden was observed in the liver. Optimization of the treatment regimen should be performed to fully potentiate the in vivo efficacy of our lead molecule, particularly in the lung, the main target organ of M. tuberculosis.

Mapping the transporter-substrate interactions of the Trypanosoma cruzi NB1 nucleobase transporter reveals the basis for its high affinity and selectivity for hypoxanthine and guanine and lack of nucleoside uptake

Trypanosoma cruzi is a protozoan parasite and the etiological agent of Chagas disease, a debilitating and sometimes fatal disease that continues to spread to new areas. Yet, Chagas disease is still only treated with two related nitro compounds that are insufficiently effective and cause severe side effects. Nucleotide metabolism is one of the known vulnerabilities of T. cruzi, as they are auxotrophic for purines, and nucleoside analogues have been shown to have genuine promise against this parasite in vitro and in vivo. Since purine antimetabolites require efficient uptake through transporters, we here report a detailed characterisation of the T. cruzi NB1 nucleobase transporter with the aim of elucidating the interactions between TcrNB1 and its substrates and finding the positions that can be altered in the design of novel antimetabolites without losing transportability. Systematically determining the inhibition constants (Ki) of purine analogues for TcrNB1 yielded their Gibbs free energy of interaction, ΔG0. Pairwise comparisons of substrate (hypoxanthine, guanine, adenine) and analogues allowed us to determine that optimal binding affinity by TcrNB1 requires interactions with all four nitrogen residues of the purine ring, with N1 and N9, in protonation state, functioning as presumed hydrogen bond donors and unprotonated N3 and N7 as hydrogen bond acceptors. This is the same interaction pattern as we previously described for the main nucleobase transporters of Trypanosoma brucei spp. and Leishmania major and makes it the first of the ENT-family genes that is functionally as well as genetically conserved between the three main kinetoplast pathogens.

N6-methyladenosine in 5′ UTR does not promote translation initiation

The most abundant N6-methyladenosine (m6A) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by m6A remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single m6A does not affect translation yields, the kinetics of translation initiation complex assembly, or start codon recognition both under permissive growth and following exposure to oxidative stress. Cryoelectron microscopy (cryo-EM) structures of the late preinitiation complex reveal that m6A purine ring established stacking interactions with an arginine side chain of the initiation factor eIF2α, although with only a marginal energy contribution, as estimated computationally. These findings provide molecular insights into m6A interactions with the initiation complex and suggest that the subtle stabilization is unlikely to affect the translation dynamics under homeostatic conditions or stress.

Biomimetic synthesis of single-crystalline anhydrous xanthine nanoplates in an aqueous solution with high reflectivity.

Biogenic purine crystals can function in vision as light scatters, mirrors, and multilayer reflectors and produce structural colors or depolarization for camouflage. Xanthine crystals form irregular multifocal mirrors in the median ocellus of Archaeognatha. It is important to broaden the study of crystallization strategies to obtain organic crystals with purine rings in the laboratory. In this work, a facile one-step synthesis route to fabricate bio-inspired xanthine crystals is reported for the first time. The obtained rhomboidal xanthine nanoplates have similar morphology and size to biogenic xanthine crystals. Their length and thickness are about 2-4 μm and 50 nm, respectively. Lattice parameters, crystal structure, formation mechanism and optical properties of synthetic single-crystalline xanthine nanoplates were investigated in detail in this work. The obtained xanthine nanoplate crystals are proposed to be anhydrous xanthine with monoclinic symmetry, and the xanthine nanoplates mainly expose the (100) plane. It is proposed that the anhydrous xanthine nanoplates are formed via an amorphous xanthine intermediate precursor. The synthetic anhydrous xanthine nanoplates exhibit excellent optical properties, including high diffuse reflectivity, strong depolarization and pearlescent luster. This work provides a new design to synthesize bio-inspired organic molecular crystals with excellent optical properties.

Spectroscopic, Quantum Chemical and Molecular Docking Studies on N-(9H-Purin-6-yl) Benzamide: A Potent Antimalarial Agent

This study presents a comprehensive analysis of N-(9H-purin-6-yl) Benzamide (NPB) using a combination of Density Functional Theory (DFT) calculations and experimental techniques. The molecular configuration of NPB was optimized using DFT/B3LYP method employing the 6-311++G (d,p) basis set. The fundamental frequencies were calculated and assigned, which agree well with the experimental results. The UV-Vis spectroscopic analyses, HOMO-LUMO energy gap assessment, Molecular Electrostatic Potential calculation, and Mulliken charge analysis, Fukui function calculation and Natural bond orbital analysis were performed for the NPB molecule. The UV-Visible spectral analysis, which predicts the transition of bonding and anti-bonding π-electrons from the purine ring to the aromatic ring of the NPB molecule. A smaller energy gap in the HOMO-LUMO analysis reveals that the NPB molecule is more reactive and Mulliken atomic charge distribution analysis indicates that the carbon atoms are highly influenced by their substituents. Natural Bond Orbital (NBO) analysis was employed to investigate the bonding within the NPB molecule. The Fukui function analysis indicates that the biological activity of the NPB molecule. In order to analyze the structure of NPB molecule, the thermodynamic properties in the temperature range 100–1000 K were obtained by thermodynamic analysis software SHERMO calculator. The molecular docking analysis was carried out for antimalarial proteins (5ZNC, 2BMA, 7E27, 7E26) using auto-docking simulations. This computational method confirms the bioactivity and drug-likeness parameters of the NPB molecule. The molecular docking results predicts the formation of hydrogen bonds between the ligand (NPB) and the protein receptors. Based on these findings, this study establishes that the distinctive methodology applied to identify NPB molecule as a potential candidate for an antimalarial drug designing, which is suitable for in vivo and in vitro investigations.

Exploring molecular fingerprints of different drugs having bile interaction: a stepping stone towards better drug delivery.

Bile acids are amphiphilic substances produced naturally in humans. In the context of drug delivery and dosage form design, it is critical to understand whether a drug interacts with bile inside the gastrointestinal (GI) tract or not. This study focuses on the identification of structural fingerprints/features important for bile interaction. Molecular modelling methods such as Bayesian classification and recursive partitioning (RP) studies are executed to find important fingerprints/features for the bile interaction. For the Bayesian classification study, the ROC score of 0.837 and 0.950 are found for the training set and the test set compounds, respectively. The fluorine-containing aliphatic/aromatic group, the branched chain of the alkyl group containing hydroxyl moiety and the phenothiazine ring etc. are identified as good fingerprints having a positive contribution towards bile interactions, whereas, the bad fingerprints such as free carboxylate group, purine, and pyrimidine ring etc. have a negative contribution towards bile interactions. The best tree (tree ID: 1) from the RP study classifies the bile interacting or non-interacting compounds with a ROC score of 0.941 for the training and 0.875 for the test set. Additionally, SARpy and QSAR-Co analyses are also been performed to classify compounds as bile interacting/non-interacting. Moreover, forty-six recently FDA-approved drugs have been screened by the developed SARpy and QSAR-Co models to assess their bile interaction properties. Overall, this attempt may facilitate the researchers to identify bile interacting/non-interacting molecules in a faster way and help in the design of formulations and target-specific drug development.

Selective coordination of polyazin sapanisertib with halide vacancy for printable mesoscopic perovskite solar cells

The mitigation of under-coordinated Pb2+ (halide vacancy) defect remains an imperative challenge in the perovskite solar cells, especially printable mesoscopic perovskite solar cells (FP-PSCs). Here we report a commercial-available polyazin anticancer drug Sapanisertib as coordination passivator of halide vacancies in FP-PSCs, thereby achieving the photoelectric conversion efficiency (PCE) to 18.46%, along with a record certified PCE of 18.27%. In polazin Sapanisertib (Sap), there exists two kinds of nitrogen atoms: in-aromatic ring (in purine and oxazole rings, IAR-Ns) and out-aromatic ring (substituted amino groups, OAR-Ns). Through multiple characterizations, and DFT calculations show that substituted amino groups OAR-Ns hardly get interaction with the halide vacancy due to the distribution of charge density in Sapanisertib. Our work suggests that the selective coordination is of great significance for the design of high-performance passivators for printable mesoscopic perovskite solar cells.

Design, synthesis and biological evaluation of Nucleosidic CD99 inhibitors that selectively reduce Ewing sarcoma viability.

Ewing Sarcoma (ES) is a cancer of bone and soft tissues affecting mostly children and young adults. Aggressive progression and poor prognosis of this malignancy call for novel and targeted treatments. CD99 is a transmembrane protein that is abundantly expressed on ES cells and is a diagnostic marker for the disease. ES cells are selectively sensitive to CD99 inhibition compared to most normal cells and other tumors. Therefore, CD99 is a good molecular target for ES treatment. Clofarabine and cladribine are two FDA approved drugs that are administered for their inhibitory acts on DNA synthesis to treat relapsed or refractory acute lymphoblastic and myeloid leukemia. They have also been shown to directly bind to CD99 and inhibit ES growth through a distinct mechanism. In the current study, we designed, synthesized and tested new ES specific derivatives of both drugs that would continue to target CD99 but with expected reduction in cellular membrane permeability and rendered unsuitable for inhibiting DNA synthesis. By using commercially available clofarabine and cladribine purine nucleoside analogs, we modified the primary alcohol moiety at the deoxyribose C-5' terminal site to suppress phosphorylation and thus inhibition of subsequent DNA synthesis pathways. In addition, we incorporated a variety of polar groups in the ribose and purine rings to reduce membrane permeability and investigated the effects of configurational changes in the sugar moiety. Among 26 new derivatives, we identified two compounds, BK50164 and BK60106, that cause cell death specifically in ES primarily due to inhibition of CD99 but not via inhibition of DNA synthesis. These findings provide a road map for the future development selective CD99 inhibitors for targeted treatment of ES.

Influence of the Solvent on the Stability of Aminopurine Tautomers and Properties of the Amino Group

Amino derivatives of purine (2-, 6-, 8-, and N-NH2) have found many applications in biochemistry. This paper presents the results of a systematic computational study of the substituent and solvent effects in these systems. The issues considered are the electron-donating properties of NH2, its geometry, π-electron delocalization in purine rings and tautomeric stability. Calculations were performed in ten environments, with 1 < ε < 109, using the polarizable continuum model of solvation. Electron-donating properties were quantitatively described by cSAR (charge of the substituent active region) parameter and π-electron delocalization by using the HOMA (harmonic oscillator model of aromaticity) index. In aminopurines, NH2 proximity interactions depend on its position and the tautomer. The results show that they are the main factor determining how solvation affects the electron-donating strength and geometry of NH2. Proximity with the NH∙∙∙HN repulsive interaction between the NH2 and endocyclic NH group results in stronger solvent effects than the proximity with two attractive NH∙∙∙N interactions. The effect of amino and nitro (previously studied) substitution on aromaticity was compared; these two groups have, in most cases, the opposite effect, with the largest being in N1H and N3H purine tautomers. The amino group has a smaller effect on the tautomeric preferences of purine than the nitro group. Only in 8-aminopurine do tautomeric preferences change: N7H is more stable than N9H in H2O.

Identification of compounds with activity against Trypanosoma cruzi within a collection of synthetic nucleoside analogs.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and it is the most important neglected tropical disease in the Americas. Two drugs are available to treat the infection, but their efficacy in the chronic stage of the disease, when most cases are diagnosed, is reduced. Their tolerability is also hindered by common adverse effects, making the development of safer and efficacious alternatives a pressing need. T. cruzi is unable to synthesize purines de novo, relying on a purine salvage pathway to acquire these from its host, making it an attractive target for the development of new drugs. We evaluated the anti-parasitic activity of 23 purine analogs with different substitutions in the complementary chains of their purine rings. We sequentially screened the compounds' capacity to inhibit parasite growth, their toxicity in Vero and HepG2 cells, and their specific capacity to inhibit the development of amastigotes. We then used in-silico docking to identify their likely targets. Eight compounds showed specific anti-parasitic activity, with IC50 values ranging from 2.42 to 8.16 μM. Adenine phosphoribosyl transferase, and hypoxanthine-guanine phosphoribosyl transferase, are their most likely targets. Our results illustrate the potential role of the purine salvage pathway as a target route for the development of alternative treatments against T. cruzi infection, highlithing the apparent importance of specific substitutions, like the presence of benzene groups in the C8 position of the purine ring, consistently associated with a high and specific anti-parasitic activity.

Complete Structure Assignment of Azathioprine as a Proton-Deficient Nucleic Acid Analogue Using 1H-13C Long-Range Heteronuclear Single Quantum Multiple Bond Correlation.

In this Note, the successful structural assignment of a proton-deficient nucleic acid analogue using the 1H-13C long-range heteronuclear single quantum multiple bond correlation (LR-HSQMBC) technique is described. LR-HSQMBC is a 2D NMR technique for the sensitive detection of weak C-H spin couplings. The immunosuppressant drug, azathioprine, served as the target compound. The LR-HSQMBC measurements revealed the existence of covalent bonds between the purine and imidazole rings based on observations of 5JCH and 6JCH with good sensitivity.

Bioactive Compounds Profile of Solok Arabica Coffee Analyzed by GC-MS Method

The type of coffee affects the compounds in it, the environment, and the soil. One of the areas in West Sumatera where a Coffee Producer is Solok Regency. The kind of coffee that is cultivated in Solok is Arabica coffee. The height of the planting point has an influence on the taste, so Solok Arabica coffee has a different taste from the flavors of other Arabica coffees that are widely spread throughout Indonesia. This study aims to determine the compounds contained in Solok Arabica coffee, which was roasted at 200oC for 10 minutes. The compound detection in Solok Arabica coffee was carried out using gas chromatography-mass spectrometry (GC-MS). The results of GC-MS analysis detected 25 compounds in Solok Arabica coffee at 200oC for 10 minutes, and 4 of them were detected in large quantities, namely pyridine, caffeine, n-hexadecanoic acid, and butyl 9,12-octadecadienoate with amounts between 70-97 m / z. Pyridine is a benzene derivative by replacing CH groups with N atoms, which are toxic to humans because they can cause nausea, vomiting, headache, dizziness, and irritation when in contact with the skin. Caffeine is the main bioactive component of the purine ring system in coffee. The sensory test method used to determine the typical Arabica Coffee of “Ranah Minang” is cupping to assess the taste of the coffee. n-hexadecanoic acid is a saturated fatty acid with antioxidant, hypocholesterolemic, nematicide, anti-androgenic, hemolytic, pesticide, lubricant, 5-alpha reductase inhibitor, antipsychotic, and anti-inflammatory activity.

Resonance Hyper-Raman Spectroscopy of Nucleotides and Polynucleotides.

We applied 532 nm-excited two-photon resonance hyper-Raman (RHR) spectroscopy to nucleotides (dA, dG, dT, and dC) to obtain fundamental knowledge about their spectral patterns. The RHR spectrum of each nucleotide exhibited various modes of the purine and pyrimidine rings, showing the ability to acquire the structural information on the chromophore. The band positions of the RHR spectrum and the 266 nm-excited one-photon UV-resonance Raman (UVRR) spectrum were identical, while the intensity patterns differed. The peak assignments of the RHR bands were given by analogy to the UVRR spectrum. In examining the polynucleotides, which form a double-stranded helix through intermolecular hydrogen bonds, some RHR bands were found to be available as structural markers. Moreover, several overtone and combination bands were detected above 2000 cm-1. The frequencies of dA and dG were accounted for by considering the involvement of the vibration of dA at 1579 cm-1 and that of dG at 1482 cm-1, respectively. Multiple vibronically active modes were seen for dT and dC. HR spectroscopy offers unique information on the fundamental, combination, and overtone modes of dA and dG, of which the multiple electronic states are involved in the resonance process.

Highly Chemoselective Synthesis of Purino[3,2-c]oxazoles via the Asymmetric Dearomative [3+2] Cycloaddition of Purines with Donor-Acceptor Oxiranes.

A Ni(II)/bisoxazoline-catalyzed asymmetric dearomative [3+2] cycloaddition of substituted purines with donor-acceptor oxiranes was developed. This reaction, which proceeds via highly chemoselective C-C bond cleavage of the oxiranes, accesses chiral purino[3,2-c]oxazole compounds (≤99% ee after enrichment via crystallization). The electronic effects of the purine ring determine the reactivity of the substrate. The general applicability of this method was illustrated by gram-scale synthesis, the diverse transformations of the product, and the promising biological activities of selected derivatives.