Search

Anomeric purine-purine DNA represents a new recognition system with strands in parallel orientation. This work investigates the new heterochiral system and the positional impact of nucleobase functionalization. Tracts of anomeric isoguanine/8-aza-7-deazaisoguanine base pairs with 5-aza-7-deazaguanine were embedded in anomeric Watson-Crick DNA. It was discovered that stable purine-purine base pairs are formed in anomeric DNA. Nucleobase functionalization of the novel base pair system with short ethynyl and bulky octadiynyl chains showed that the position of functionalization is critical. From

The title compound 3-phenyltetrahydropyrimido[4,5-c]pyridazine 2′-deoxyribonucleoside [systematic name: 6-(2-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-3-phenylpyrimido[4,5-c]pyridazin-7-one monohydrate, C17H18N4O4·H2O, 1] shows two conformations in the crystalline state and the two conformers (1a and 1b) adopt different sugar puckers. The sugar residue of 1a shows a C2′-endo S-type conformation, while 1b displays a C3′-endo N-type sugar pucker. Both conformers adopt similar anti conformations around the N-glycosylic bonds, with χ = −97.5 (3)° for conformer 1a and χ = −103.8 (3)° for conformer 1b. The extended crystalline network is stabilized by several intermolecular hydrogen bonds involving nucleoside and water molecules. The nucleobases and phenyl substituents of the two conformers (1a and 1b) are stacked and display a reverse alignment. A Hirshfeld surface analysis supports the hydrogen-bonding pattern, while curvedness surfaces visualize the stacking interactions of neighbouring molecules. The recognition face of nucleoside 1 for base-pair formation mimics that of 2′-deoxythymidine. Nucleoside 1 shows two pK a values: 1.8 for protonation and 11.2 for deprotonation. DNA oligonucleotides containing nucleoside 1 were synthesized and hybridized with complementary DNA strands. Nucleoside 1 forms a stable base pair with dA which is as stable as the canonical dA–dT pair. The bidentate 1–dA base pair is strengthened by a third hydrogen bond provided by the dA analogue 3-bromopyrazolo[3,4-d]pyrimidine-4,6-diamine 2′-deoxyribofuranoside (4). By this, duplex stability is increased and the suggested base-pairing patterns are supported.

The Watson–Crick coding system depends on the molecular recognition of complementary purine and pyrimidine bases. Now, the construction of hybrid DNAs with Watson–Crick and purine–purine base pairs decorated with dendritic side chains was performed. Oligonucleotides with single and multiple incorporations of 5‐aza‐7‐deaza‐2′‐deoxyguanosine, its tripropargylamine derivative, and 2′‐deoxyisoguanosine were synthesized. Duplex stability decreased if single modified purine–purine base pairs were inserted, but increased if pyrene residues were introduced by click chemistry. A growing number of consecutive 5‐aza‐7‐deazaguanine–isoguanine base pairs led to strong stepwise duplex stabilization, a phenomenon not observed for the guanine–isoguanine base pair. Spacious residues are well accommodated in the large groove of purine–purine DNA tracts. Changes to the global helical structure monitored by circular dichroism spectroscopy show the impact of functionalization to the global double‐helix structure. This study explores new areas of molecular recognition realized by purine base pairs that are complementary in hydrogen bonding, but not in size, relative to canonical pairs., Fit in the groove: Hybrid DNAs with Watson–Crick and purine–purine base pairs decorated with dendritic side chains are prepared. Space‐demanding side chains introduced into the 7‐position of 5‐aza‐7‐deazaguanine–isoguanine base pairs are well accommodated in the large groove of purine–purine DNA and have a positive impact on helix stability.

Purine-purine base pairs represent an alternative recognition system to the purine-pyrimidine pairing reported by Watson and Crick. Modified purines are the source for non-canonical interactions. To mimic dG-dC interactions, 2'-deoxyisoguanosine (

Purine-2,6-diamine and 8-aza-7-deaza-7-bromopurine-2,6-diamine 2'-deoxyribonucleosides (1 and 2) were implemented in isothermal DNA strand displacement reactions. Nucleoside 1 is a weak stabilizer of dA-dT base pairs, nucleoside 2 evokes strong stabilization. Strand displacement reactions used single-stranded invaders with single and multiple incorporations of stabilizers. Displacement is driven by negative enthalpy changes between target and displaced duplex. Toeholds are not required. Two new environmental sensitive fluorescent pyrene sensors were developed to monitor the progress of displacement reactions. Pyrene was connected to the nucleobase in the invader or to a dendritic linker in the output strand. Both new sensors were constructed by click chemistry; phosphoramidites and oligonucleotides were prepared. Sensors show monomer or excimer emission. Fluorescence intensity changes when the displacement reaction progresses. Our work demonstrates that strand displacement with base pair stabilizers is applicable to DNA, RNA and to related biopolymers with applications in chemical biology, nanotechnology and medicinal diagnostics.

DNA strand displacement is a technique to exchange one strand of a double stranded DNA by another strand (invader). It is an isothermal, enzyme free method driven by single stranded overhangs (toeholds) and is employed in DNA amplification, mismatch detection and nanotechnology. We discovered that anomeric (α/β) DNA can be used for heterochiral strand displacement. Homochiral DNA in β-D configuration was transformed to heterochiral DNA in α-D/β-D configuration and further to homochiral DNA with both strands in α-D configuration. Single stranded α-D DNA acts as invader. Herein, new anomeric displacement systems with and without toeholds were designed. Due to their resistance against enzymatic degradation, the systems are applicable to living cells. The light-up intercalator ethidium bromide is used as fluorescence sensor to follow the progress of displacement. Anomeric DNA displacement shows benefits over canonical DNA in view of toehold free displacement and simple detection by ethidium bromide.

Stabilization of DNA is beneficial for many applications in the fields of DNA therapeutics, diagnostics, and materials science. Now, this phenomenon is studied on heterochiral DNA, an autonomous DNA recognition system with complementary strands in α‐D and β‐D configuration showing parallel strand orientation. The 12‐mer heterochiral duplexes were constructed from anomeric (α/β‐D) oligonucleotide single‐strands. Purine‐2,6‐diamine and 8‐aza‐7‐deaza‐7‐bromopurine‐2,6‐diamine 2′‐deoxyribonucleosides having the capability to form tridentate base pairs with dT were used to strengthen the stability of the dA–dT base pair. T m data and thermodynamic values obtained from UV melting profiles indicated that the 8‐aza‐7‐deaza 2′‐deoxyribonucleoside decorated with a bromo substituent is so far the most efficient stabilizer for heterochiral DNA. Compared with that, the stabilizing effect of the purine‐2,6‐diamine 2′‐deoxyribonucleoside is low. Global changes of helix structures were identified by circular dichroism (CD) spectra during melting., Base pair stabilization: Heterochiral parallel duplexes represent an autonomous recognition system constructed from anomeric (α/β‐D) oligonucleotides. The naturally occurring purine‐2,6‐diamine and the artificial 8‐aza‐7‐deaza‐7‐bromopurine nucleosides 1 and 2 strengthen the dA–dT base pair. The 8‐aza‐7‐deazapurine nucleoside decorated with a bromo substituent is so far the most efficient stabilizer for this pairing system.

7-Functionalized 8-aza-7-deaza-2'-deoxyisoguanine and 8-aza-7-deaza-2-aminoadenine 2'-deoxyribonucleosides decorated with fluorescent pyrene or benzofuran sensor tags or clickable side chains with terminal triple bonds were synthesized. 8-Aza-7-deaza-7-iodo-2-amino-2'-deoxyadenosine was used as the central intermediate and was accessible by an improved two-step glycosylation/amination protocol. Functionalization of position-7 was performed either on 8-aza-7-deaza-7-iodo-2-amino-2'-deoxyadenosine followed by selective deamination of the 2-amino group or on 7-iodinated 8-aza-7-deaza-2'-deoxyisoguanosine. Sonogashira and Suzuki-Miyaura cross-coupling reactions were employed for this purpose. Octadiynyl side chains were selected as linkers for click reactions with azido pyrenes. KTaut values calculated from H2O/dioxane mixtures revealed that side chains have a significant influence on the tautomeric equilibrium. Photophysical properties (fluorescence, solvatochromism, and quantum yields) of the new 8-aza-7-deazapurine nucleosides with fluorescent side chains were determined. Remarkably, a strong excimer fluorescence in H2O was observed for pyrene dye conjugates of 8-aza-7-deazaisoguanine and 2-aminoadenine nucleosides with a long linker. In other solvents including methanol, excimer fluorescence was negligible. The 2-aminoadenine and isoguanine nucleosides with the 8-aza-7-deazapurine skeleton expand the class of nucleosides applicable to fluorescence detection with respect to diagnostic and therapeutic purposes.

A mild and efficient scheme for the synthesis of 3-substituted functionalized flavones was developed. The reaction of flavanone and glyoxylic acid in ethanol in the presence of the catalytic amount of sulphuric acid at reflux temperature for 2–3 h yielded good to excellent functionalized flavones. As per present scenario for the synthesis of different substituted flavones, this method represents mild reaction conditions, low-cost catalyst, broad substrate scope along with high yields, which makes it more credible and handy synthetic strategy.

The special nucleobase recognition pattern of 5-aza-7-deazaguanine nucleosides makes them valuable for construction of homo purine DNA, silver-mediated base pairs, and expansion of the four letter genetic coding system. To widen the utility of 5-aza-7-deazaguanine nucleosides, side chains were introduced at position-7 of the nucleobase. As key compounds, 7-iodo nucleosides were synthesized. Nucleobase anion glycosylation of the iodo derivative of isobutyrylated 5-aza-7-deazaguanine with the bromo sugar of 2,3,5-tri-O-benzoyl-1-O-acetyl-d-ribofuranose gave the pure β-D anomeric N-9 glycosylation product (67%), whereas one-pot Vorbruggen conditions gave only 42% of the iodinated nucleoside. The noniodinated nucleoside was formed in 84%. For the synthesis of 2'-deoxyribonucleosides, anion glycosylation performed with Hoffer's 2'-deoxyhalogenose yielded an anomeric mixture (α-D = 33% and β-D = 39%) of 2'-deoxyribonucleosides. Various side chain derivatives were prepared from nonprotected nucleosides by Pd-assisted Sonogashira or Suzuki-Miyaura cross-coupling. Among the functionalized ribonucleosides and anomeric 2'-deoxyribonucleosides, some of them showed strong fluorescence. Benzofuran and pyrene derivatives display high quantum yields in non-aqueous solvents and solvatochromism. Single-crystal X-ray analysis of 7-iodo-5-aza-7-deaza-2'-deoxyguanosine displayed intermolecular iodo-oxygen interactions in the crystal and channels filled with solvent molecules.

Nucleoside configuration (α-d vs. β-d), nucleobase substituents, and the helical DNA environment of silver-mediated 5-aza-7-deazaguanine-cytosine base pairs have a strong impact on DNA stability. This has been demonstrated by investigations on oligonucleotide duplexes with silver-mediated base pairs of α-d and β-d anomeric 5-aza-7-deaza-2'-deoxyguanosines and anomeric 2'-deoxycytidines incorporated in 12-mer duplexes. To this end, a new synthetic protocol has been developed to access the pure anomers of 5-aza-7-deaza-2'-deoxyguanosine by glycosylation of either the protected nucleobase or its salt followed by separation of the glycosylation products by crystallization and chromatography. Thermal stability measurements were performed on duplexes with α-d/α-d and β-d/β-d homo base pairs or α-d/β-d and β-d/α-d hybrid pairs within two sequence environments, positions 6 or 7, of oligonucleotide duplexes. The respective Tm stability increases observed after silver ion addition differ significantly. Homo base pairs with β-d/β-d or α-d/α-d nucleoside combinations are more stable than α-d/β-d hybrid base pairs. The positional switch of silver-ion-mediated base pairs has a significant impact on stability. Nucleobase substituents introduced at the 5-position of the dC site of silver-mediated base pairs affect base pair stability to a minor extent. Our investigation might lead to applications in the construction of bioinspired nanodevices, in DNA diagnostics, or metal-DNA hybrid materials.

8-Furylimidazolo-2′-deoxycytidine (furImidC), C14H14N4O5, is a fluorescent analogue of 2′-deoxycytidine, also displaying the same recognition face. As a constituent of DNA, furImidC forms extraordinarily strong silver-mediated self-pairs. Crystal structure determination revealed that furImidC adopts two types of disordered residues: the sugar unit and the furyl moiety. The disorder of the sugar residue amounts to an 87:13 split. The disorder of the furyl ring results from axial chirality at the C8—C2′′ bond connecting the nucleobase to the heterocycle. The two atropisomers are present in unequal proportions [occupancies of 0.69 (2) and 0.31 (2)], and the nucleobase and the furyl moiety are coplanar. Considering the atomic sites with predominant occupancy, an anti conformation with χ = − 147.2 (7)° was found at the glycosylic bond and the 2′-deoxyribosyl moiety shows a C2′-endo (S, 2 T 1) conformation, with P = 160.0°. A 1H NMR-based conformational analysis of the furanose puckering revealed that the S conformation predominates also in solution. In the solid state, two neighbouring furImidC molecules are arranged in a head-to-tail fashion, but with a notable tilt of the molecules with respect to each other. Consequently, one N—H...N hydrogen bond is found for neighbouring molecules within one layer, while a second N—H...N hydrogen bond is formed to a molecule of an adjacent layer. In addition, hydrogen bonding is observed between the nucleobase and the sugar residue. A Hirshfeld surface analysis was performed to visualize the intermolecular interactions observed in the X-ray study. In addition, the fluorescence spectra of furImidC were measured in solvents of different polarity and viscosity. furImidC responds to microenvironmental changes (polarity and viscosity), which is explained by a hindered rotation of the furyl residue in solvents of high viscosity.

The change of the recognition face of 5-aza-7-deazaguanine bridgehead nucleosides with respect to purine nucleosides permits the construction of new purine-purine or purine-pyrimidine base pairs in DNA and RNA. Clickable derivatives of 5-aza-7-deazaguanine were synthesized by introducing ethynyl, 1,7-octadiynyl, and tripropargylamino side chains in the 7-position of the 5-aza-7-deazapurine moiety by Sonogashira cross-coupling. Click reactions were performed with 1-azidomethylpyrene by the copper-catalyzed azide-alkyne cycloaddition. The copper(I)-catalyzed click reaction on the tripropargylamino nucleoside was significantly faster and higher yielding than that for nucleosides carrying linear alkynyl chains. Also, this reaction could be performed with copper(II) as the catalyst. An autocatalyzed cycle was suggested in which the click product acts as a catalyst. Pyrene click adducts of linear alkynylated nucleosides showed pyrene monomer emission, while tripropargylamino adducts showed monomer and excimer fluorescence. The fluorescence intensities of the 5-aza-7-deazaguanine nucleosides were higher than those of their 7-deazaguanine counterparts. The reported clickable nucleosides can be utilized to functionalize or to cross-link monomeric nucleosides or DNA for diagnostic or imaging purposes and other applications in nucleic acid chemistry and biotechnology.

7-Iodo-5-aza-7-de­aza­guanosine represents a base-modified nucleoside with an entirely different recognition pattern as the parent purine com­pound. It shows an anti conformation at the glycosylic bond and an N conformation (O4′-endo) for the ribose moiety. Packing is controlled by hydrogen bonds and by a 7-iodo contact to 2′-oxygen of the ribose moiety., The positional change of nitro­gen-7 of the RNA constituent guanosine to the bridgehead position-5 leads to the base-modified nucleoside 5-aza-7-de­aza­guanosine. Contrary to guanosine, this mol­ecule cannot form Hoogsteen base pairs and the Watson–Crick proton donor site N3—H becomes a proton-acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable ‘all-purine’ DNA and DNA with silver-mediated base pairs. The present work reports the single-crystal X-ray structure of 7-iodo-5-aza-7-de­aza­guanosine, C10H12IN5O5 (1). The iodinated nucleoside shows an anti conformation at the glycosylic bond and an N conformation (O4′-endo) for the ribose moiety, with an anti­periplanar orientation of the 5′-hy­droxy group. Crystal packing is controlled by inter­actions between nucleobase and sugar moieties. The 7-iodo substituent forms a contact to oxygen-2′ of the ribose moiety. Self-pairing of the nucleobases does not take place. A Hirshfeld surface analysis of 1 highlights the contacts of the nucleobase and sugar moiety (O—H⋯O and N—H⋯O). The concept of pK-value differences to evaluate base-pair stability was applied to purine–purine base pairing and stable base pairs were predicted for the construction of ‘all-purine’ RNA. Furthermore, the 7-iodo substituent of 1 was functionalized with benzo­furan to detect motional constraints by fluorescence spectroscopy.

Curcumin, a constituent of Curcuma longa, has shown numerous biological and pharmacological activities, including antidiabetic effects. Here, a novel series of curcumin analogues were synthesized and evaluated for in vitro inhibition of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which plays a key role in the onset and progression of diabetic complications. Biological activity studies showed that all the curcuminoids exhibited moderate to good AR inhibitory (ARI) activities compared with that of the quercetin standard. Importantly, compounds 8d, 8h, 9c, 9e, and 10g demonstrated promising ARI activities, with the 50% inhibitory concentration (IC50) values of 5.73, 5.95, 5.11, 5.78, and 5.10 &micro, M, respectively. Four other compounds exhibited IC50 values in the range of 6.04&ndash, 6.18 &micro, M. Methyl and methoxy derivatives showed a remarkable ARI potential compared with that of other substitutions on the aromatic ring. Molecular docking experiments demonstrated that the most active curcuminoid (10g) was able to favorably bind in the active site of the AR enzyme. The potent ARI activities exhibited by the curcuminoids were attributed to their substitution patterns on the aromatic moiety, which may provide novel leads in the development of therapeutics for the treatment of diabetic complications.

A simple, cost-effective, environmentally benign, and efficient one-pot tandem approach to the synthesis of pharmaceutically important 1-aryl-1H-tetrazole-5-amines 3a-k and 4a-k has been described. The reaction utilized 1-phenyl thiourea, which was generated in situ from aqueous ammonia and isocyanates 1a-k, for the formation of heterocumenes using sodium azide, triethylamine, and ceric ammonium nitrate (CAN) to obtain various aryl-substituted 1H-tetrazole-5-amines (3a-k) in good to excellent yields.

Coccinia grandis (L.) fruits (CGFs) are commonly used for culinary purposes and has several therapeutic applications in the Southeast Asia. The aim of this work was to evaluate phytochemical profile, aldose reductase inhibitory (ARI), and antioxidant activities of CGF extract. The CGFs were extracted with different solvents including petroleum ether, dichloromethane, acetone, methanol, and water. The highest yield of total extractable compounds (34.82%) and phenolic content (11.7 ± 0.43 mg of GAE/g dried extract) was found in methanol extract, whereas water extract showed the maximum content of total flavonoids (82.8 ± 7.8 mg QE/g dried extract). Gas chromatography–mass spectroscopy (GC–MS) analysis of methanol and water extract revealed the presence of flavonoids, phenolic compounds, alkaloids, and glycosides in the CGFs. Results of the in vitro ARI activity against partially purified bovine lens aldose reductase showed that methanol extract of CGFs exhibited 96.6% ARI activity at IC50 value 6.12 µg/mL followed by water extract 89.1% with the IC50 value 6.50 µg/mL. In addition, methanol and water extracts of CGF showed strong antioxidant activities including ABTS*+ scavenging, DPPH* scavenging, and hydroxyl radical scavenging. Our results suggest that high percentage of both flavonoids and phenolic contents in the CGFs are correlated with the ARI and antioxidant activities. The fruits of C. grandis are thus potential bifunctional agents with ARI and antioxidant activities that can be used for the prevention and management of DM and associated diseases.

Coccinia grandis (L.) fruits (CGFs) are commonly used for culinary purposes and has several therapeutic applications in the Southeast Asia. The aim of this work was to evaluate phytochemical profile, aldose reductase inhibitory (ARI), and antioxidant activities of CGF extract. The CGFs were extracted with different solvents including petroleum ether, dichloromethane, acetone, methanol, and water. The highest yield of total extractable compounds (34.82%) and phenolic content (11.7 ± 0.43 mg of GAE/g dried extract) was found in methanol extract, whereas water extract showed the maximum content of total flavonoids (82.8 ± 7.8 mg QE/g dried extract). Gas chromatography–mass spectroscopy (GC–MS) analysis of methanol and water extract revealed the presence of flavonoids, phenolic compounds, alkaloids, and glycosides in the CGFs. Results of the in vitro ARI activity against partially purified bovine lens aldose reductase showed that methanol extract of CGFs exhibited 96.6% ARI activity at IC50 value 6.12 µg/mL followed by water extract 89.1% with the IC50 value 6.50 µg/mL. In addition, methanol and water extracts of CGF showed strong antioxidant activities including ABTS*+ scavenging, DPPH* scavenging, and hydroxyl radical scavenging. Our results suggest that high percentage of both flavonoids and phenolic contents in the CGFs are correlated with the ARI and antioxidant activities. The fruits of C. grandis are thus potential bifunctional agents with ARI and antioxidant activities that can be used for the prevention and management of DM and associated diseases.

Calcium hydroxide was found to be an efficient mild base for the one-pot synthesis of curcumin and its analogues obtained by condensation of one equivalent of acetyl acetone with two equivalents of corresponding aromatic aldehyde. The present protocol offers various advantages such as high yields, inexpensive easily available mild base, easy workup and eco-friendly method.

Ammonium iodide in open air decomposes to ammonia and iodine. The in situ generated iodine has been used for cyclization of 2?-hydroxychalcones to corresponding flavones under solvent free conditions with good to excellent yields. This method would serve as an attractive alternative to the existing methods for synthesis of flavones and use of toxic molecular iodine is avoided.

Crystalline manganese carbonate was found to be a versatile green, non corrosive and environmental friendly catalyst for transesterification of vegetable oils. Its use as catalyst in the transesterification process involving methanol and vegetable oils (palm, rapeseed, groundnut, coconut and caster oils) resulted in a conversion rate of 80% - 95% in the production of biodiesel. The chemical composition of the obtained biodiesel was studied by GC-MS analysis and showed the presence of linoleic, oleic, palmitic, and stearic acids methyl esters to be the major compounds. Manganese carbonate in comparison with other solid catalysts was found to decrease the reaction time and temperature concomitant with an increase of biodiesel yield. Finally, the effect of various parameters including methanol quantity, catalyst amount, reaction time and temperatures on the production of biodiesel was investigated.

Biodiesel production from Argemone mexicana seed oil using crystalline manganese carbonate This communication explores the feasibility of biodiesel production from a weed plant Argemone mexicana seed oil and an efficient catalyst crystalline manganese carbonate. To the best of the authors' knowledge, this is the first study making use of pure, crystalline, ash colored manganese carbonate as a heterogeneous catalyst for the production of methyl esters as fuel from Argemone mexicana seed oil. The optimum process conditions for the conversion of Argemone mexicana oil to its methyl ester by transesterification required 1% manganese carbonate as catalyst with alcohol to oil ratio 5:1 at 60°C to yield biodiesel of 99.99% purity. The methyl esters obtained were examined by Gas chromatography analysis.