Synthesis of modified fragments of fibrinogen and their effect on the activity of proteolytic enzymes

New analogues of the Gly-Pro-Arg and Arg-Gly-Asp fragments of fibrinogen were synthesized: Gly-Pro-Arg-Pro (I), Gly-Pro-Arg-Pro-Met-OMe (II), Gly-Pro-Arg-Pro-Phe (III), Gly-Pro-Arg-Pro-Asp (IV), Gly-Pro-Arg-Pro-Glu (V), and Arg-Asn-Trp-Asp (VI). Their effect on the activity of proteases of various types was studied with the method of lysis of fibrin plates. All the peptides were found to inhibit plasmin activity (by 60–85%) and the γ-subunit of nerve growth factor (by 55–93%). Tetrapeptide (VI) proved to be an effective inhibitor of tissue activator of plasminogen and the γ-subunit of nerve growth factor (by 96 and 93%, respectively). The peptides exerted practically no effect on the activity of urokinase and moderately inhibited the activity of streptokinase [(III), IV), and (VI)], papain [(I), (II), IV), and (VI)], subtilisin [(V) and (VI)], α-chymotrypsin [(III), (V), and VI)], and Bacillus subtilis metalloprotease (VI). They inhibit trypsin [except for (I) and (III)] when applied on fibrin plates at a concentration of 1 × 10^?2 M, while, at the concentration of 1 × 10^?3 M, (I) and (II) induced an increase in proteolytic activity by 35 and 47%, respectively.     

Distorted tetrahedral nickel-nitrosyl complexes: spectroscopic characterization and electronic structure

The linear nickel-nitrosyl complex [Ni(NO)(L3)] supported by a highly hindered tridentate nitrogen-based ligand, hydrotris(3-tertiary butyl-5-isopropyl-1-pyrazolyl)borate (denoted as L3), was prepared by the reaction of the potassium salt of the ligand with the nickel-nitrosyl precursor [Ni(NO)(Br)(PPh ₃ ) ₂ ]. The obtained nitrosyl complexes as well as the corresponding chlorido complexes [Ni(NO)(Cl)(PPh ₃ ) ₂ ] and [Ni(Cl)(L3)] were characterized by X-ray crystallography and different spectroscopic methods including IR/far-IR, UV–Vis, NMR, and multi-edge X-ray absorption spectroscopy at the Ni K-, Ni L-, Cl K-, and P K-edges. For comparative electronic structure analysis we also performed DFT calculations to further elucidate the electronic structure of [Ni(NO)(L3)]. These results provide the nickel oxidation state and the character of the Ni-NO bond. The complex [Ni(NO)(L3)] is best described as [Ni ^II (NO ^– )(L3)], and the spectroscopic results indicate that the phosphane complexes have a similar [Ni ^II (NO ^– )(X)(PPh ₃ ) ₂ ] ground state.     

Potential antidiabetic activity and molecular docking studies of novel synthesized 3.6-dimethyl-5-oxo-pyrido[3,4-f][1,2,4]triazepino[2,3-a]benzimidazole and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole derivatives

Diabetes affects a large population of the globe and is considered as a leading cause of death. Many synthetic and natural inhibitors have been developed for diabetes treatment. Herein, we report the potential antidiabetic activity of two new heterocyclic systems, namely 3.6-dimethyl-5-oxo-pyrido[3,4f][1,2,4]triazepino[2,3-a]benzimidazole (I) and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole (II) against three related enzymes: α-amylase, α-glucosidase and β-galactosidase. Compounds I and II were synthesized by the action of DMF-DMA and dimethyl sulfate in the presence of water on 2-methyl-3H-benzimidazolo[1,2b][1,2,4]triazepin-4(5H)-one, and are characterized by single X-ray diffraction. The binding interaction modes in the active sites of I and II and targeted enzymes (stable complexes ligand-receptor) are emphasized using the molecular docking approach by applying the Lamarckian genetic algorithm method. Furthermore, plausible mechanisms have been proposed explaining their synthesis. Hirshfeld surface analysis reveals the nature of molecular interactions and fingerprint plots provide information about the percentage contribution from each individual molecular contact to the structure surface.

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Graphical abstract Left Molecular packing of 1,4-dimethyl-2-oxo-pyrimido[1,2-a]benzimidazole hydrate. Right Docking active site of α-glucosidase

     

Synthesis and primary evaluation of the hepatoprotective properties of novel pyrimidine derivatives

Based on the active ingredient of the drug Ximedon (1,2-dihydro-4,6-dimethyl-1-N-(2-hydroxyethyl)pyrimidone-2, referred below to as pyrimidine (I), novel derivatives containing biogenic acids: succinic, L-ascorbic, para-aminobenzoic, nicotinic, and L-2-amino-4-(methylthio)butanoic (L-methionine) acids have been synthesized. The parameters of acute toxicity (LD₅₀) have been studied. The antitoxic effect of the compounds upon the injury by the hepatotropic poison carbon tetrachloride has been examined as the primary evaluation of their hepatoprotective properties. It has been found that, according to toxicological safety, the compounds synthesized belong to classes III and IV (moderately and little toxic compounds). The conjugates of pyrimidine (I) with ascorbic acid and methionine (LD₅₀ more than 5400 mg/kg) are least toxic. Pyrimidine (I) and its derivatives possess the antitoxic activity upon acute poisoning with carbon tetrachloride; the combined injection of carbon tetrachloride with pyrimidine (I) or its derivatives leads to an increase in the survival of animals and the normalization of the integral functional parameters, weight and body temperature, which decrease upon toxic injury. In addition, pyrimidine (I) and some of its derivatives (conjugates with L-ascorbic, succinic, para-aminobenzoic, and nicotinic acids) decrease the weight coefficients of the liver and kidneys (the organ-to-body-weight ratio) and the activity of transaminases, the markers of hepatic cytolysis, which increase upon toxic injury with carbon tetrachloride. The area of the pathological injury of the liver by steatosis and necrosis decreases by the action of pyrimidine (I) and its novel derivatives (conjugates with L-ascorbic, succinic, and nicotinic acids) two to three times. Advantages of pyrimidine (I) and its novel derivatives over the hepatoprotective drug Thiotriazolin have been revealed.     

Aromaticity of graphene nanoflakes in a new way: fragment analysis by combination of the nucleus-independent chemical shifts and the anisotropy of current induced density

A graphene nanoflake (GNF) is a polycyclic aromatic hydrocarbon (PAH) with a huge two-dimensional π-conjugated carbon material in which a central benzene ring is surrounded by identical benzene-type rings through infinite alternant method. In this paper, we explore the structure-aromaticity relationship of the GNFs and the GNFs with hollow sites (GNFHs) by combining the nucleus-independent chemical shifts (NICS) with the anisotropy of the current induced density (ACID). Firstly, the benzene is a typical aromatic molecule (NICS = ?9.671 ppm), GNFs 1-6 is darned with benzene and the corresponding GNFHs 1′-6′. Secondly, the NICS values of GNFs 1-6 alternately vary: ?1.214 (1) > ?13.847 (2) < ?2.662 (3) > ?14.530 (4) < ?3.932 (5) > ?13.978 (6) ppm, the GNFs (2, 4, 6) with even fragments of annulene have larger aromaticity than that of GNFs (1, 3, 5) with odd fragments of annulene. Significantly, the NICS values of GNFs 1-6 can also be fragment analyzed by the NICS values and ACID of benzene and corresponding GNFHs 1′-6′. The NICS values for GNFs (2, 4, 6) can be roughly estimated by the NICS value of benzene minus the NICS value of the GNFHs (2′, 4′, 6′), respectively. The NICS values for GNFs (1, 3, 5) can be roughly estimated by the NICS value of the GNFHs (1′, 3′, 5′) minus the NICS value of benzene, respectively. We hope that the present work can provide a simple and reliable method for the rational design of the GNF with aromaticity, which may be used to understand the origin of the graphene nanoflake aromatic properties.     

Preparation,Structure, and Potent Antifouling Activity of Sclerotioramine Derivatives

A series of 30 sclerotioramine derivatives (2–31) of the natural compound, (+)-sclerotiorin (1), has been successfully semi-synthesized by a one-step reaction with high yields (up to 80%). The structures of these new derivatives were established by extensive spectroscopic methods and single-crystal X-ray diffraction analysis for 3, 6, and 10. (+)-Sclerotiorin (1) and its semisynthetic derivatives (2–31) were evaluated for their antifouling activity. Most of them except 6, 7, 8, 12, and 28 showed potent antifouling activity against the larval settlement of the barnacle Balanus amphitrite. More interestingly, most of the aromatic amino-derivatives (13–17, 19–21, 23, 25–27, and 29–31) showed strong antifouling activity; however, only two aliphatic amino-derivatives (5 and 10) had the activity.     

Comparison of structural features of three new cis-dioxomolybdenum(VI) complexes with 2-hydroxy-1-naphthaldehyde-S-methylisothiosemicarbazone: Possible role of intermolecular interactions on the geometry of the cis-MoO2 unit

Three closely related [MoO₂(L)(ML)] complexes, where L is the 2-hydroxy-1-naphthaldehyde-S-methylisothiosemicarbazone ligand, and ML is EtOH (I), Py (II) and DMSO (III), were synthesized, characterized by NMR and IR spectra, and their X-ray crystal structures were determined. The crystal structure properties of these three closely related complexes were compared. Two cis-Mo-O bond lengths were almost the same in the crystal structure of complexes II and III, while in complex I a significant difference between the two cis-Mo-O bond lengths was observed. At the same time, the geometry of L ligand in complex I is different, compared to II and III. DFT calculations on the isolated molecule I, as well as geometrical analysis of the complexes indicate that intramolecular interactions are not responsible for these structural differences. On the other hand, the pattern of intermolecular contacts in the crystal structure of I differs from those observed in II and III. Analyses indicate that differences in cis-Mo-O bond lengths and in the geometry of ligand L could be related to intermolecular interactions. These results suggest the possibility that in enzymes oxotransferases or in their model systems, the Mo-O bond length could be designed by the interactions of chelate ligands with the surroundings.     

Design and synthesis of an indol derivative as antibacterial agent against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Several indole derivatives with antibacterial activity have been prepared using different protocols; however, some require special reagents and conditions. The aim of this study involved the synthesis of some indole derivatives using estrone and OTBS-estrone as chemical tools. The synthesis of the indole derivatives involves reactions such as follows: (1) synthesis of two indol derivatives (4 or 5) by reaction of estrone or OTBS-estrone with phenylhydrazine in medium acid; (2) reaction of 4 or 5 with 6-cloro-1-hexyne in medium basic to form two hexynyl-indol (7 or 8); (3) preparation of indol-propargylic alcohol derivatives (10 or 11) by reaction of benzaldehyde with 7 or 8 in medium basic; (4) synthesis of indol-aldehydes (12 or 13) via oxidation of 10 or 11 with DMSO; (5) synthesis of indeno-indol-carbaldehyde (15 or 16) via alkynylation/cyclization of 12 or 13 with hexyne in presence of copper(II); (6) preparation indeno-indol-carbaldehyde complex (19 or 20) via alkynylation/cyclization of 12 or 13 with 1-(hex-5-yn-1-yl)-2-phenyl-1H-imidazole. The antibacterial effect exerted by the indol-steroid derivatives against Streptococcus pneumoniae and Staphylococcus aureus bacteria was evaluated using dilution method and the minimum inhibitory concentration (MIC). The results showed that only the compound 19 inhibit the growth bacterial of S. aureus. In conclusion, these data indicate that antibacterial activity of 19 can be due mainly to functional groups involved in the chemical structure in comparison with the compounds studied.     

Flu virion as a substrate for proteolytic enzymes

The proteolysis of flu virions of the strain A/Puerto Rico/8/34 (subtype H1N1) by enzymes of various classes was studied to develop an approach to the study of the structural organization and interaction of the major protein components of the virion: hemagglutinin (HA), transmembrane homotrimeric glycoprotein, and matrix protein M1 forming a layer under the lipid membrane. Among the tested proteolytic enzymes and enzymic preparations (thermolysin, trypsin, chymotrypsin, subtilisin Carlsberg, pronase, papain, and bromelain), the cysteine proteases bromelain and papain and the enzymic preparation pronase efficiently removed HA ectodomains, while chymotrypsin, trypsin, and subtilisin Carlsberg deleted only a part of them. An analysis by MALDI TOF mass spectrometry allowed us to locate the sites of HA hydrolysis by various enzymic preparations. Bromelain, papain, trypsin, and pronase split the polypeptide chain after the K177 residue located before the transmembrane domain (HA₂ 185–211). Subtilisin Carlsberg hydrolyzed the peptide bond at other neighboring points: after L178 (a major site) or V176. The hydrolytic activity of bromelain measured by a highly specific chromogenic substrate of cysteine proteases Glp-Phe-Ala-pNA was almost three times higher in the presence of 5 mM β-mercaptoethanol than in the presence of 50 mM. However, the complete removal of ectodomains of HA by the high-and low-activity enzyme required identical time intervals. In the absence of the reducing reagent, the removal of HA by bromelain proceeded a little more slowly and was accompanied by significant fragmentation of protein M1. The action of trans-epoxysuccinyl-L-leucylamido)(4-guanidino)butane (E-64), a specific inhibitor of cysteine proteases, and HgCl₂ On the hydrolysis of proteins HA and M1 by bromelain was investigated.     

Theoretical study of the regioselective cyclization of enaminones in the construction of benzofurans and indoles

A theoretical study was undertaken regarding the regioselective Lewis acid-promoted intramolecular cyclization of novel enaminones 1-3 leading to the corresponding benzofurans 4-5 and indoles 6. The density functional theory (DFT) and hard and soft acids and bases (HSAB) principle provided data to describe the electronic effects of the substituents in the reactivity of the benzene ring and the enaminone moiety. The condensed and local Fukui functions for nucleophilic and electrophilic attacks of the reactants accounted for the experimentally observed preference, in regard to precursors 1-3, of the cyclization between the C6′ carbon (rather than the C2′ carbon) of the benzene ring and the C3 center of the enaminone moiety.

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Graphical Abstract A theoretical study (DFT/HSAB) describes the electronic effects of the substituents in the reactivity of the benzene ring and the enaminone moiety of enaminones I to explain their Lewis acid-promoted regioselective intramolecular cyclization, which exclusively leads to the corresponding benzofurans and indoles II

     

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (L _OL 1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (L _OL 2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (L _OL 3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (L _imz 1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(L _OL 1)(CH₃CN)]PF₆ (CuL _OL 1), [Cu(I)(L _OL 2)(CH₃CN)]PF₆ (CuL _OL 2), [Cu(I)(L _OL 3)(CH₃CN)]PF₆ (CuL _OL 3), [Cu(I)(L _imz 1)(CH₃CN)₂]PF₆ (CuL _imz 1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH₃CN)]PF₆ (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H₂) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuL _OL 3 ≈ CuL _OL 1 > CuBIMZ > CuL _OL 2 > CuL _imz 1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-l-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuL _imz 1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.     

DNA sequence-specific ligands: XVI. Series of the DBP(<Emphasis Type="Italic">n</Emphasis>) fluorescent dimeric bisbenzimidazoles with 1,4-piperazine-containing linkers

A novel series of the DBP(n) fluorescent symmetric dimeric bisbenzimidazoles in which the bisbenzimidazole fragments were attached to an oligomeric linker with the 1,4-piperazine residue in its center were prepared. The DBP(n) molecules were distinguished by the number of methylene groups n (where n = 1, 2, 3, 4) in the linker. The DBP(n) synthesis was based on a condensation of the monomeric bisbenzimidazole (MB) with 1,4-piperazinedialkylcarbonic acids. The ability of the DBP(n) dimeric bisbenzimidazoles to form complexes with the double-stranded DNA was demonstrated by a complex of physicochemical methods, including spectroscopy in the visual UV-area, circular dichroism (CD), and fluorescence. The DBP(1–4) molecules were localized in the DNA minor groove by the CD method with the use of cholesteric liquid-crystalline dispersions (CLCD) of the double-stranded DNA. The DBP(n) dimeric bisbenzimidazoles were easily soluble in water, penetrated through cellular and nuclear membranes, and stained DNA in living cells distinct from the previously synthesized DB(n) series.     

Differential alkaloid profile in <Emphasis Type="Italic">Uncaria tomentosa</Emphasis> micropropagated plantlets and root cultures

The alkaloids of Uncaria tomentosa micropropagated plantlets and root cultures were isolated and identified by NMR and mass spectrometry. Plantlets yielded pteropodine (1), isopteropodine (2), mitraphylline (3), isomitraphylline (4), uncarine F (5), speciophylline (6), rhynchophylline (7) and isorhynchophylline (8). In plantlets growing under continuous light, tetracyclic alkaloids 7 and 8 decreased from 20 ± 1.8 at 2 months to 2.2 ± 0.33 mg/g dry wt at 6 months, while the pentacyclic alkaloids 1–4 increased from 7.7 ± 1.4 to 15 ± 0.05 mg/g dry wt, supporting their biogenetic conversion. Micropropagated plantlets produced four times more alkaloids (27.6 ± 3.1 mg/g dry wt) than greenhouse plants. Plantlet roots yielded 3, 4, 8 and the glucoindole alkaloids 3α-dihydrocadambine (9) and dolichantoside (10), the last one not previously found in Uncaria.     

The effects of (22S,23S)- and (22R,23R)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-ones on biosynthesis of cholesteryl esters and activity of acyl-CoA:Cholesterol acyl transferase in Hep G2 cells

Novel synthetic oxysterols (22S,23S)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (I) and (22R,23R)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (II) influenced biosynthesis of cholesteryl esters from [¹⁴C]acetate (85% and 180% of control at 5 μM concentration) in the human hepatoma Hep G2 cell line. Ketosterol (I) increased the level of cholesteryl ester biosynthesis from [¹⁴C]oleate in Hep G2 cells in a dose dependent manner, whereas the level of cholesteryl esters biosynthesis in the presence of ketosterol (II) reached the maximal value (269±20% of control) at 1 μM concentration of this compound. In a cell free system ketosterol (I) increased the rate of ACAT-dependent cholesterol acylation similar to 25-hydroxycholesterol, however, ketosterol (II)), efficiently stimulated an initial rate of ACAT-catalyzed cholesterol esterification, followed by rapid inactivation of this enzyme.     

Investigation of the photochemical properties of biopterin and its reduced forms

UV irradiation (270–390 nm, 20 min, I = 3.2 W m^?2) of deaerated biopterin solution containing electron donor (Na₂-EDTA) led to the formation of 7,8-dihydrobiopterin (H ₂ BPT), which, when excited, underwent reduction to form 5,6,7,8-tetrahydrobiopterin (H ₄ BPT). Protonated molecules of H₄BPT were resistant to oxidation by O₂ both in the “dark” incubated and UV-irradiated solutions at pH below 3.0. The rate of H₄BPT oxidation dramatically increased at pH above 3.0, and, then, up to pH 10.0, it did not change, showing no dependence on UV irradiation. At the initial stage (5 min) of H₄BPT oxidation in neutral solution, UV irradiation stimulated the accumulation of quinonoid 6,7-dihydrobiopterin (q-H ₂ BPT) in addition to H₂BPT. UV irradiation of H₂BPT induced its oxidation to biopterin and unidentified products.     

Correlation analyses on binding affinity of substituted benzenesulfonamides with carbonic anhydrase using ab initio MO calculations on their complex structures (II)

We proposed a novel QSAR (quantitative structure-activity relationship) procedure called LERE (linear expression by representative energy terms)-QSAR involving molecular calculations such as ab initio fragment molecular orbital and generalized Born/surface area ones. We applied LERE-QSAR to two datasets for the free-energy changes during complex formation between carbonic anhydrase and a series of substituted benzenesulfonamides. The first compound set (Set I) and the second one (Set II) include relatively small substituents and alkyl chains of different lengths in the benzene ring, respectively. Variation of the inhibitory activity in Set I is expressed as the combination of Hammett σ and the hydrophobic substituent constant π in classical QSAR, and variation in Set II only by π. LERE-QSAR analyses clearly revealed that effects of σ and π on the activity variations in Sets I and II are consistently explainable with the energy terms in the LERE formulation, and provide more detailed and direct information as to the binding mechanism. The proposed procedure was demonstrated to provide a quantitative basis for understanding ligand-protein interactions at the electronic and atomic levels.     

Bioactive phytochemicals from shoots and roots of <Emphasis Type="Italic">Salvia</Emphasis> species

The plants of the genus Salvia L. are important medicinal herbs of the Lamiaceae family and some of them such as S. officinalis (sage), S. miltiorrhiza (red sage, Danshen) and S. sclarea (clary sage) have been used as medicinal plants in the folk medicine of several countries. In this review, we discuss the reports that have examined Salvia species with the aim of isolation of pure compounds with different biological activities. The phytochemical analyses of various sage plants have reported 10 monoterpenoids (1–10), 1 sesquiterpenoid (11), 8 labdane (13–20), 15 ent-kaurane (21–35), 82 abietane, rearranged abietane and tanshinone (36–117), 3 icetexane (118–120), 43 clerodane (121–163), and 3 pimarane (164–166) diterpenoids with cytotoxic and antimicrobial, antiprotozoal, antioxidant, phytotoxic and insecticide effects. The other heavier terpenoids, including 3 sesterterpenes (167–169), 10 triterpenoids and β-sitosterol (170–180) have been introduced as minor bioactive compounds in the sage plants. Sahandinone (107), 6,7-dehydroroyleanone, 7-α-acetoxyroyleanone (40), and tanshinone like diterpenoids have been isolated from the roots’ extracts of different Salvia species. On the other hand, several radical scavenger phenolic compounds like simple phenolics and caffeic acid derivatives (181–201) including rosmarinic acid, flavonoids (202–217) as well as phenolic diterpenoids, such as carnosol and carnosic acid have been isolated from the aerial parts of these plants. One pyrrole (218) and 3 antimicrobial oxylipins (219–221) are among the other less detected constituents in the members of Salvias. Furthermore, sages also synthesize antifungal, antileishmanial and antimalarial phytochemicals in their roots and shoots, which are reviewed in this paper. We also examine the allelopathic phenomena and the ecologically important phytochemicals identified in different parts of the sage plants. Finally, antifeedant and insecticide phenomena, which are due to the presence of volatile monoterpenes and clerodane diterpenes in these plants, are discussed. Considering the presence of diverse biologically active phytochemicals in the sage plants, they can be suggested as suitable candidates for the formulation of valuable natural medicines.     

Four mononuclear platinum(II) complexes: synthesis,DNA/BSA binding,DNA cleavage and cytotoxicity

Four new platinum(II) complexes: Pt^II L1·H₂O (C1, H₂ L1 = C₂₀H₁₆N₂O₂), Pt^II L2Cl₂ (C2, L2 = C₂₂H₁₆N₂O₂), Pt^II L3Cl₂·H₂O (C3, L3 = C₂₀H₁₆N₂), Pt^II L4Cl₂·0.4H₂O (C4, L4 = C₁₈H₁₄N₄) have been synthesized and characterized by using various physico-chemical techniques. The binding interaction of the four platinum(II) complexes C1–C4 with calf thymus (CT)-DNA has been investigated by UV–Vis and fluorescence emission spectrometry. The apparent binding constant (K _app) values follow the order: C3 > C1 > C2 > C4. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with the four platinum(II) complexes C1–C4 showed that the quenching mechanism might be a static quenching procedure. For C1–C4, the number of binding sites was about one for BSA and the binding constants follow the order: C3 (7.08 × 10⁵M^?1) > C1 (2.82 × 10⁵M^?1) > C2 (0.85 × 10⁵M^?1) > C4 (0.15 × 10⁵M^?1). With the single condition change such as absence of an external agent, the DNA cleavage abilities of C3 exhibit remarkable changes. In addition, the cytotoxicity of C3 in vitro on tumor cells lines (MCF-7, HepG2 and HT29) were examined by MTT and showed better antitumor effects on the tested cells.     

Organic Solvent-Tolerant Marine Microorganisms as Catalysts for Kinetic Resolution of Cyclic β-Hydroxy Ketones

Chiral cyclic β-hydroxy ketones represent key motifs in the production of natural products of biological interest. Although the molecules are structurally simple, they require cumbersome synthetic steps to get access to them and their synthesis remains a challenge in organic chemistry. In this report, we describe a straightforward approach to enantiomerically enriched (R)- and (S)-3-hydroxycyclopentanone 2a, (R)- and (S)-3-hydroxycyclohexanone 2b, and (R)- and (S)-3-hydroxycycloheptanone 2c involving a transesterification resolution of the racemates using whole cells of marine microorganisms as catalysts and vinyl acetate the acyl donor and solvent. Twenty-six strains from a wide collection of isolates from marine sediments were screened, and seven strains were found to markedly catalyze the resolution in an asymmetric fashion. Using the strain Serratia sp., (R)-2a was isolated in 27% yield with 92% ee and (S)-2a in 65% yield with 43% ee, corresponding to an E-value of 37; (R)-2b was isolated in 25% yield with 91% ee and (S)-2b in 67% yield with 39% ee, corresponding to an E-value of 40; and (R)-2c was isolated in 30% yield with 96% ee and (S)-2c in 63% yield with 63% ee, corresponding to an E-value of 75.     

A computational approach to design energetic ionic liquids

The present work deals with the theoretical estimation of ion-pair binding energies and the energetic properties of four ion pairs formed by combining the 1-butyl-2,4-dinitro-3-methyl imidazolium ion with nitrate (I), perchlorate (II), dinitramide (III), or 3,5-dinitro-1,2,4-triazolate (IV) anions. The counterpoise-corrected ion-pair binding energies were calculated for each ion pair at the B3LYP/6-311+G(d,p) level of theory. Results show that the cation–anion interaction is strongest for ion pair I and weakest for IV, indicating that the nitrate (I) has a greater tendency to exist as a stable ionic salt whereas the 3,5-dinitro-1,2,4-triazolate (IV) may exist as an ionic liquid. Natural bond orbital (NBO) analysis and electrostatic potential (ESP) mapping revealed that charge transfer occurs in all of the ion pairs, but is greatest (0.25e) for ion pair I and smallest (0.03e) for IV, resulting in ion pair I being the least polarized. A nucleus-independent chemical shift (NICS) study revealed that the aromaticity of the 1-butyl-2,4-dinitro-3-methyl imidazolium ion significantly increases in ion pair IV, indicating that this has the greatest charge delocalization among all of the four ion pairs considered. Studies of thermodynamic and detonation properties showed that ion pair II is the most energetic ion pair in terms of its detonation velocity (D = 7.5 km s^?1) and detonation pressure (P = 23.1 GPa). It is also envisaged that ion pair IV would exist as an energetic azolium azolate type ionic liquid that could be conveniently used as a secondary explosive characterized by detonation parameters D and P of 6.9 km s^?1 and 19.3 GPa, respectively. These values are comparable to those of conventional explosives such as TNT.