Melanogenesis inhibitory activity of a 7-O-9′-linked neolignan from Alpinia galanga fruit

An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC₅₀ = 7.3 μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9′-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 phenylpropanoids (2–15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC₅₀ = 2.5 μM), 1′S-1′-acetoxychavicol acetate (2, 5.0 μM), and 1′S-1′-acetoxyeugenol acetate (3, 5.6 μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1′-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9′-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1′ (IC₅₀ = 1.9 μM) and 2′ (4.5 μM)] and racemic mixtures [(±)-1 (2.2 μM) and (±)-2 (4.4 μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1–3 inhibited tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity.     

Design of a new fluorescent probe: Pyrrole/imidazole hairpin polyamides with pyrene conjugation at their γ-turn

Fluorophores that are conjugated with N-methylpyrrole-N-methylimidazole (Py–Im) polyamides postulates versatile applications in biological and physicochemical studies. Here, we show the design and synthesis of new types of pyrene-conjugated hairpin Py–Im polyamides (1–5). We evaluated the steady state fluorescence of the synthesized conjugates (1–5) in the presence and absence of oligodeoxynucleotides 5′-CGTATGGACTCGG-3′ (ODN 1) and 5′-CCGAGTCCATACG-3′ (ODN 2) and observed a distinct increase in emission at 386 nm with conjugates 4 and 5. Notably, conjugate 5 that contains a β-alanine linker had a stronger binding affinity (K_D = 1.73 × 10^?8 M) than that of conjugate 4 (K_D = 1.74 × 10^?6 M). Our data suggests that Py–Im polyamides containing pyrene fluorophore with a β-alanine linker at the γ-turn NH₂ position can be developed as the competent fluorescent DNA-binding probes.     

Syntheses and crystal structures of trimethyltin(IV) coordination polymers based on mixed ligands of 5-nitroisophthalate and 2,2′(4,4′)-bipy or phen

The trimethyltin(IV) polymer [(Me₃Sn)₂(nip) · EtOH]_n (1) of 5-nitroisophthalic acid (H₂nip) and its three derivatives with mixed organic N-donor ligands 2,2′-bipy [(Me₃Sn)₂(nip) · 2H₂O] · [(Me₃Sn)₂(nip) · H₂O] · 2(2,2′-bipy) (2) 4,4′-bipy {[(Me₃Sn)₂(nip)]₂(4,4′-bipy)}_n (3) or phen [(Me₃Sn)₂(nip) · H₂O] · (phen) (4) have been synthesized by the reaction of trimethyltin(IV) chloride and H₂nip when sodium ethoxide was added in the presence of 2,2′-bipy 4,4′-bipy or phen. All complexes 1–4 were characterized by elemental, IR, ¹H, ¹³C, and ¹¹⁹Sn NMR spectroscopy and X-ray crystallography analyses. Crystal, data collection and structure refinement parameters for complexes 1, 2, 3 and 4 are shown in Table 1, Table 2, respectively. The X-ray data showed the geometries of all the tin atoms in complexes 1–4 are trigonal bipyramidal. The X-ray analysis of 1 showed that the structure was a polymeric infinite chain with neighboring triorganotin centers being linked by dicarboxylate ligands and hydrogen bonds were found between adjacent chains. For 2, two different monomers were found, in one monomer, Me₃Sn were coordinated to both carboxyl groups of the ligand and water molecules were coordinated to the two Sn(IV) centers. In the other monomer, water molecules were coordinated to only one Sn center. Co-crystallized2,2′-bipy was found in 2 and a 2D supermolecular structure was formed via O–H⋯O and O–H⋯N (N atoms derived from 2,2′-bipy) hydrogen bonds. In 3 however, a 2D polymeric block was formed due to the inversion center of the 4,4′-bipy. For 4, due to the O–H⋯O and O–H⋯N (N atoms derived from phen) hydrogen bonds and intermolecular Sn⋯O bonds, a 2D polymeric structure was formed.     

Two new anti-HBV lignans from Herpetospermum caudigerum

Two new lignans, named (+)-(7′S, 7″S, 8′R, 8″R)-4, 4′, 4″-trihydroxy-3, 5′, 3″-trimethoxy-7-oxo-8-ene [8-3′, 7′-O-9″, 8′-8″, 9′-O-7″] lignoid (1) and (1S)-4-Hydroxy-3-[2-(4-hydroxy-3-methoxy-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-5-methoxy-benzaldehyde (2), along with five known (3–7) ones, have been isolated from the 95% ethanol extract of the seeds of Herpetospermum caudigerum Wall. The structures of the new compounds, including the absolute configurations, were elucidated by spectroscopic and CD analysis. Compounds 1, 2, and 7 displayed inhibitory activities on HBsAg secretion with IC₅₀ values of 20.5, 0.34, and 4.89 μM, while 1, 2, and 7 displayed inhibitory activities on HBeAg secretion with IC₅₀ values of 3.54, 4.83 × 10⁻⁴, and 8.02 μM, and cytotoxicity on HepG 2.2.15 cells with CC₅₀ values of 12.7, 2.96 × 10⁵, and 11.4 μM, respectively.     

Syntheses,structures, and magnetic properties of heterobimetallic complexes based on tetracyanometallic building blocks

Two tetracyanometalate building blocks, [Fe(5,5′-dmbipy)(CN)₄]^? (2) and [Fe(4,4′-dmbipy)(CN)₄]^? (3) (5,5′-dmbipy = 5,5′-dimethyl-2,2′-bipyridine; 4,4′-dmbipy = 4,4′-dimethyl-2,2′-bipyridine), and two cyano-bridged heterobimetallic complexes, [Cu₂(bpca)₂(H₂O)₂Fe₂(5,5′-dmbipy)₂(CN)₈] · 2[Cu(bpca)Fe(5,5′-dmbipy)(CN)₄] · 4H₂O (4) and [Cu(bpca)Fe(4,4′-dmbipy)(CN)₄]_n (5) (bpca = bis(2-pyridylcarbonyl)amidate), have been synthesized and structurally characterized. Complex 4 contains two dinuclear and one tetranuclear heterobimetallic clusters in an asymmetric unit whereas the structure of complex 5 features a one-dimensional heterobimetallic zigzag chain. The Cu(II) ion is penta-coordinated in the form of a distorted square-based pyramid. Magnetic studies show ferromagnetic coupling between Cu(II) and Fe(III) ions with g = 2.28, J₁ = 2.64 cm^?1, J₂ = 5.40 cm^?1 and TIP = ?2.36 × 10^?3 for complex 4, and g = 2.17, J = 4.82 cm^?1 and zJ′ = 0.029 cm^?1 for complex 5.     

X-ray structures of dinuclear copper(I) and polynuclear copper(II) complexes with the 2,4-bis(cyanamido)cyclobutane-1,3-dione dianion

From the 2,4-bis(cyanamido)cyclobutane-1,3-dione dianion (2,4-NCNsq²⁻), two copper complexes [Cu₂(PPh₃)₄(PhCN)₂(μ-2,4-NCNsq)] · PhCN (1) and [Cu(dien)(μ-2,4-NCNsq) · H₂O]_n (2) have been synthesized and characterized by IR and electronic absorption spectroscopies. Their structures have been determined by X-ray crystallography. Complex 1 is a dinuclear copper(I) compound with a 2,4-NCNsq²⁻ ligand bridging two copper atoms through the nitrile nitrogen atoms. Complex 2 appears as a 3D network constituted of copper(II) atoms bridged by 2,4-NCNsq²⁻ dianions. This complex presents an unexpected coordination mode of the bis(cyanamido) ligands which are both coordinated via the nitrile functions and via the amido nitrogen atoms of the NCN groups.     

Design,synthesis, and DNA binding characteristics of a group of orthogonally positioned diamino,N-formamido,pyrrole- and imidazole-containing polyamides

Orthogonally positioned diamino/dicationic polyamides (PAs) have good water solubility and enhanced binding affinity, whilst retaining DNA minor groove and sequence specificity compared to their monoamino/monocationic counterparts. The synthesis and DNA binding properties of the following diamino PAs: f-IPI (3a), f-IPP (4), f-PIP (5), and f-PPP (6) are described. P denotes the site where a 1-propylamino group is attached to the N1-position of the heterocycle. Binding of the diamino PAs to DNA was assessed by DNase I footprinting, thermal denaturation, circular dichroism titration, biosensor surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) studies. According to SPR studies, f-IPI (3a) bound more strongly (K_eq = 2.4 × 10⁸ M^?1) and with comparable sequence selectivity to its cognate sequence 5′-ACGCGT-3′ when compared to its monoamino analog f-IPI (1). The binding of f-IPI (3a) to 5′-ACGCGT-3′ via the stacked dimer motif was balanced between enthalpy and entropy, and that was quite different from the enthalpy-driven binding of its monoamino parent f-IPI (1). f-IPP (4) also bound more strongly to its cognate sequence 5′-ATGCAT-3′ (K_eq = 7.4 × 10⁶ M^?1) via the side-by-side stacked motif than its monoamino analog f-IPP (2a). Although f-PPP (6) bound via a 1:1 motif, it bound strongly to its cognate sequence 5′-AAATTT-3′ (K_eq = 4.8 × 10⁷ M^?1), 15-times higher than the binding of its monoamino analog f-PPP (2c), albeit f-PPP bound via the stacked motif. Finally, f-PIP (5) bound to its target sequence 5′-ATCGAT-3′ as a stacked dimer and it has the lowest affinity among the diamino PAs tested (K_eq <1 × 10⁵ M^?1). This was about two times lower in affinity than the binding of its monoamino analog f-PIP (2b). The results further demonstrated that the ‘core rules’ of DNA recognition by monoamino PAs also apply to their diamino analogs. Specifically, PAs that contain a stacked IP core structure bind most strongly (highest binding constants) to their cognate GC doublet, followed by the binding of PAs with a stacked PP structure to two degenerate AT base pairs, and finally the binding of PAs with a PI core to their cognate CG doublet.     

Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory,antioxidant and antimicrobial agents

A novel series of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (3) have been prepared by the Claisen–Schmidt condensation of 1-(2,4-dimethoxy-phenyl)-ethanone (1) and substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (2). Substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (2) were prepared by Vilsmeir–Haack reaction on acetophenonephenylhydrazones to offer the target compounds. The structures of the compounds were established by IR, ¹H NMR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory (TNF-α and IL-6 inhibitory assays), antioxidant (DPPH free radical scavenging assay) and antimicrobial activities (agar diffusion method) against some pathogenic bacteria and fungi. Of 10 compounds screened, compounds 3a, 3c and 3g exhibited promising IL-6 inhibitory (35–70% inhibition, 10 μM), free radical scavenging (25–35% DPPH activity) and antimicrobial activities (MIC 100 μg/mL and 250 μg/mL) at varied concentrations. The structure–activity relationship (SAR) and in silico drug relevant properties (HBD, HBA, PSA, c Log P, molecular weight, E_HOMO and E_LUMO) further confirmed that the compounds are potential lead compounds for future drug discovery study. Toxicity of the compounds was evaluated theoretically and experimentally and revealed to be nontoxic except 3d and 3j.     

Synthesis,crystal structure and magnetic properties of the spin crossover system [Fe(pq)3]2+

Three new compounds formulated (ClO₄)₂[Fe(pq)₃] (1), (BF₄)₂[Fe(pq)₃] · EtOH (2) and {(ClO₄)[MnCr(C₂O₄)₃][Fe(pq)₂(H₂O)₂]} (3), where pq is 2,2′-pyridylquinoline, have been synthesised and characterised. Despite the different crystal packing exhibited by 1 and 2, the cationic species [Fe(pq)₃]²⁺ are structurally quite similar. At 293 K, the Fe–N bond lengths are characteristic of the iron(II) in the high-spin state. In contrast to 1, 2 undergoes a continuous spin transition. Indeed, at 95 K its structure experiences a noticeable change in the Fe–N bonds and angles, i.e. the Fe–N bonds shorten by 0.194 Å on the average. The magnetic behaviour confirms that 1 is fully high-spin in the 4–300 K temperature range while 2 shows a spin transition centred at T_1/2 = 150 K. The corresponding enthalpy, entropy and interaction parameter are ΔH = 7.49 kJ mol^?1, ΔS = 50 J K^?1 mol^?1and Γ = 1.35 kJ mol^?1. Compound 3 has been obtained as a microcrystalline powder. The magnetic properties of 3 point at the occurrence of ferromagnetic coupling below 100 K and the onset of a ferromagnetic ordering below 10 K (Weiss constant equal to 6.8 K). The Mössbauer spectra of 3 show the occurrence of a magnetic order at T ? 4.2 K.     

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea

A new lignan, 9′-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4–12) have been isolated from the active fractions, CHCl₃ (IC₅₀, 0.32 μg mL^?1) and EtOAc (IC₅₀, 0.55 μg mL^?1) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC₅₀ values of 3.7 and 3.3 μM, respectively. 9′-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner.     

Synthesis,characterization and biological evaluation of some novel 2,4-thiazolidinediones as potential cytotoxic,antimicrobial and antihyperglycemic agents

A series of some novel 2,4-thiazolidinediones (TZDs) (2a–x) have been synthesized and characterized by FTIR, ¹H NMR, ¹³C NMR and LC mass spectral analysis. All the synthesized compounds were evaluated for their cytotoxicity, antimicrobial and in vivo antihyperglycemic activities. Among the tested compounds for cytotoxicity using Brine Shrimp Lethality assay, compound 2t ((Z)-5-(4-((E)-3-oxo-3-(thiophen-2-yl)prop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited significant inhibitory activity at ED₅₀ value 4.00 ± 0.25 μg/mL and this level of activity was comparable to that of the reference drug podophyllotoxin with ED₅₀ value 3.61 ± 0.17 μg/mL. Antimicrobial activity was screened using agar well diffusion assay method against selected Gram-positive, Gram-negative and fungal strains and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. From the results of antimicrobial activity compound 2s ((Z)-5-(4-((E)-3-(3,5-bis(benzyloxy)phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) was found to be the most active against all the tested strains of microorganisms with MIC value 16 μg/mL. In vivo antihyperglycemic effect of twenty four TZDs (2a–x) at different doses 10, 30 and 50 mg/kg b.w (oral) were assessed using percentage reduction of plasma glucose (PG) levels in streptozotocin-induced type II diabetic rat models. From the results, the novel compound 2x ((Z)-5-(4-((E)-3-(9H-fluoren-2-yl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited considerably potent blood glucose lowering activity than that of the standard drug rosiglitazone and it could be a remarkable starting point to evaluate structure–activity relationships and to develop new lead molecules with potential cytotoxicity, antimicrobial and antihyperglycemic activities. In addition molecular docking studies were carried out against PPARγ molecular target using Molegro Virtual Docker v 4.0 to accomplish preliminary confirmation of the observed in vivo antihyperglycemic activity.     

Linear homobimetallic 4-thioacetyl-substituted NCN pincer palladium(II) and platinum(II) complexes with N-bidentate connecting units (NCN = [C6H2(CH2NMe2)2-2,6-R-4]−)

The synthesis and characterization of homobimetallic palladium and platinum complexes of type [(Me(O)CS-4-NCN–M ← N^∩N → M–NCN-4-SC(O)Me](OTf)₂ (Me(O)CS-4-NCN = [C₆H₂(CH₂NMe₂)₂-2,6-SC(O)Me-4]^?; N^∩N = 4,4′-bipyridine (bipy); M = Pd, 12; M = Pt, 13) is reported. The required bifunctional thio-acetyl NCN pincer starting compound NC(Br)N-4-SC(O)Me (2) has been synthesized by the consecutive reactions of NC(Br)N–I (I-1-C₆H₂(CH₂NMe₂)₂-3,5-Br-4) (1) with ^tBuLi, S₈ and Me(O)CCl, respectively. Chemoselective metallation at the C_aryl–Br bond was achieved by the reaction of 2 with the palladium(0) source [Pd₂(dba)₃] (3) (dba = dibenzylidene acetone). Treatment of thus formed [Pd(NCN-4-SC(O)Me)(Br)] (4) with [AgOTf] (8) (OTf = triflate, OSO₂CF₃) gave [Pd(NCN-4-SC(O)Me)(H₂O)][OTf] (9) which was further reacted with 0.5 equiv. of 4,4′-bipyridine (11a) to afford rigid-rod structured 12. When [Pt(tol)₂(SEt₂)]₂ (5) (tol = 4-tolyl) was used instead of 3, then 13 was produced via the in situ formation of [PtBr(NCN-4-SC(O)Me)] (7) and [Pt(NCN-4-SC(O)Me)(H₂O)][OTf] (10). Another possibility to synthesize 7 relied upon the subsequent reaction of 1 with 0.5 equiv. of 5 to give [PtBr(NCN-4-I)] (6) which further reacted with ^tBuLi, 1/8 S₈ and Me(O)CCl to afford 7. The cyclic voltammograms of 2, 7, and 13 are discussed.Complex 7 was structurally characterized by single crystal X-ray crystallography. Organometallic 7 crystallizes with three independent molecules in the asymmetric unit and displays a monomeric structure as commonly encountered in d⁸-metal pincer chemistry.     

Expanding the 4,4′-bipyridine ligand: Structural variation in {M(pytpy)2}2+ complexes (pytpy = 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine,M = Fe,Ni, Ru) and assembly of the hydrogen-bonded,one-dimensional polymer {[Ru(pytpy)(Hpytpy)]}n3n+

The solid state structures of [Ni(1)₂][NO₃]₂ · 2MeOH · 2H₂O, [Fe(1)₂][ClO₄]₂ · 2MeOH · 0.5H₂O, [Ru(1)₂][PF₆]₂ and [Ru(1)₂][PF₆][NO₃] (1 = 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine) are presented and the structural variation observed for the {M(1)₂}²⁺ unit is discussed. Protonation of the pendant pyridine group in [Ru(1)₂]²⁺ leads to the formation of a hydrogen-bonded, one-dimensional polymer [{Ru(1)(H1)}_n]³ⁿ⁺ exemplifed by the solid-state structure of [{Ru(1)(H1)}{Fe(NCS)₆} · 1.25H₂O]_n.     

Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa oleifera fruits

Bioassay-guided isolation and purification of the ethyl acetate extract of Moringa oleifera fruits yielded three new phenolic glycosides; 4-[(2′-O-acetyl-α-l-rhamnosyloxy) benzyl]isothiocyanate (1), 4-[(3′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate (2), and S-methyl-N-{4-[(α-l-rhamnosyloxy)benzyl]}thiocarbamate (3), together with five known phenolic glycosides (4–8). The structures of the new metabolites were determined on the basis of spectroscopic analyses including 1D- and 2D-NMR and mass spectrometry. The anti-inflammatory activity of isolated compounds was investigated with the lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cell line. It was found that 4-[(2′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate (1) possessed potent NO–inhibitory activity with an IC₅₀ value of 1.67 μM, followed by 2 (IC₅₀ = 2.66 μM), 4 (IC₅₀ = 2.71 μM), and 5 (IC₅₀ = 14.4 μM), respectively. Western blots demonstrated these compounds reduced LPS-mediated iNOS expression. In the concentration range of the IC₅₀ values, no significant cytotoxicity was noted. Structure–activity relationships following NO-release indicated: (1) the isothiocyanate group was essential for activity, (2) acetylation of the isothiocyanate derivatives at C-2′ or at C-3′ of rhamnose led to higher activity, (3) un-acetylated isothiocyanate derivatives displayed eight times less activity than the acetylated derivatives, and (4) acetylation of the thiocarbamate derivatives enhanced activity. These data indicate compounds 1, 2, 4 and 5 are responsible for the reported NO-inhibitory effect of Moringa oleifera fruits, and further studies are warranted.     

Investigations into specificity of azepinomycin for inhibition of guanase: Discrimination between the natural heterocyclic inhibitor and its synthetic nucleoside analogues

In our long and broad program to explore structure–activity relationships of the natural product azepinomycin and its analogues for inhibition of guanase, an important enzyme of purine salvage pathway of nucleic acid metabolism, it became necessary to investigate if the nucleoside analogues of the heterocycle azepinomycin, which are likely to be formed in vivo, would be more or less potent than the parent heterocycle. To this end, we have resynthesized both azepinomycin (1) and its two diastereomeric nucleoside analogues (2 and 3), employing a modified, more efficient procedure, and have biochemically screened all three compounds against a mammalian guanase. Our results indicate that the natural product is at least 200 times more potent toward inhibition of guanase as compared with its nucleoside analogues, with the observed K_i of azepinomycin (1) against the rabbit liver guanase = 2.5 (±0.6) × 10^?6 M, while K_i of Compound 2 = 1.19 (±0.02) × 10^?4 M and that of Compound 3 = 1.29 (±0.03) × 10^?4 M. It is also to be noted that while IC₅₀ value of azepinomycin against guanase in cell culture has long been reported, no inhibition studies nor K_i against a pure mammalian enzyme have ever been documented. In addition, we have, for the first time, determined the absolute stereochemistry of the 6-OH group of 2 and 3 using conformational analysis coupled with 2-D ¹H NMR NOESY     

Novel l-adenosine analogs as cardioprotective agents

Two l-nucleosides, l-3′-amino-3′-deoxy-N⁶-dimethyladenosine (l-3′-ADMdA) 1, previously synthesized in our laboratory, and the novel l-3′-amino-3′-deoxy-N⁶-methyladenosine-5′-N-methyluronamide (l-3′-AM-MECA) 2 were evaluated in an ischemia/reperfusion model on Langendorff perfused mouse heart. l-3′-ADMdA 1 was found to enhance functional recovery from ischemia (32.2 ± 3.7 cm H₂O/s % rate pressure product, compared to 21.3 ± 1.4 for the control and 30.7 ± 3.4 for adenosine) and increase the time to onset of ischemic contracture (14.5 ± 0.9 min, compared to 10.5 ± 1.0 min for the control and 13.6 ± 0.6 min for adenosine) comparable to adenosine. Consistent with the functional recovery data, decreased infarction area was seen in the case of 1 (19.1 ± 8.4, compared to 40.5 ± 7.2% for the control and 11.5 ± 2.1% for adenosine). In contrast, l-3′-AM-MECA 2 did not show significant functional recovery, increased onset of contracture, nor decreased infarction area compared to control. Unlike adenosine, neither 1 nor 2 induced cardiac standstill in mouse heart.     

Two novel erbium (III) coordination polymers with 5-nitroisophthalic acid: Syntheses and crystal structures and thermal stabilities

Two new coordination polymers, {[Er(5-nip)_1.5(2,2′-bipy)](H₂O)₂}_n (1) and {[Er(5-nip)₂] (4,4′-H₂bipy)_0.5}_n (2) (5-nip = 5-nitroisophthalic acid, 2,2′-bipy = 2,2′-bipyridyl, 4,4′-bipy = 4,4′-bipyridyl), have been synthesized by the hydrothermal reactions of erbium nitrate, 5-nitroisophthalic acid (5-H₂nip) and 2,2′-bipyridyl (for 1), and erbium nitrate, 5-nitroisophthalic acid and 4,4′-bipyridyl (for 2). X-ray diffraction analysis indicates that complex 1 exhibits a two-dimensional layer structure, while complex 2 displays a 3D architecture sustained by the strong hydrogen-bond interactions between the protonated 4,4′-bipyridyl and the carboxyl oxygen atom from [Er₂(5-nip)₄]²⁻ with 2D layer structure, and 4,4′-bipyridyl as the guest molecules exist in bilayer channel. They are characterized by the elemental analysis and IR spectroscopy. The studies for the thermal stabilities of the two complexes show that complex 2 is more stable than complex 1.     

Magnetostructural correlations and catecholase-like activities of μ-alkoxo-μ-carboxylato double bridged dinuclear and tetranuclear copper(II) complexes

Two μ-alkoxo-μ-carboxylato bridged dinuclear copper(II) complexes, [Cu₂(L¹)(μ-HCO₂)] (1) ((H₃L¹ = 1,3-bis(5-bromosalicylideneamino)-2-propanol)), [Cu₂(L²)(μ-HCO₂)] · dmf (2) (H₃L² = 1,3-bis(3,5-chlorosalicylideneamino-2-propanol)), and two μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear copper(II) complexes, [{Cu₂(L³)}₂(μ-O₂C–C(CH₃)₂–CO₂)] · 5H₂O · 3CH₃OH (3) ((H₃L³ = 1,3-bis(salicylid-deneamino)-2-propanol)) and [{Cu₂(L³)}₂(μ- O₂CCH₂–C₆H₄–CH₂CO₂)] · 2H₂O (4) have been prepared and characterized. The single crystal X-ray analysis shows that the structures of complexes 1 and 2 are dimeric with two adjacent copper(II) atoms bridged by μ-alkoxo-μ-carboxylato ligands with the Cu⋯Cu distances and Cu–O(alkoxo)–Cu angles are 3.511 Å and 132.85° for 1, 3.517 Å and 131.7° for 2, respectively. Complexes 3 and 4 consist of μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear Cu(II) complexes with mean Cu–Cu distances and Cu–O–Cu angles of 3.158 Å and 108.05° for 3 and 3.081 Å and 104.76° for 4, respectively. Magnetic measurements reveal that 1 and 2 are strong antiferromagnetically coupled with 2J = −156 and −152 cm⁻¹, respectively, while 3 and 4 exhibit ferromagnetic coupling with 2J = 86 and 155.2 cm⁻¹, respectively. The 2J values of 1–4 are linearly correlated to the Cu–O–Cu angles. Dependence of the pH at 25 °C on the reaction rate of oxidation of 3,4-di-tert-butylcatechol (3,5-dtbc) to the corresponding quinone catalyzed by 1–4 was studied. Complexes 1–4 exhibit high catecholase-like activity at pH 9.0 and 25 °C for oxidation of 3,5-di-tert-butylcatechol.     

Chemical modifications by ionic liquid-inspired cations improve the activity and the stability of formate dehydrogenase in [MMIm][Me2PO4]

The formate dehydrogenase (FDH, EC: 1.2. 1.2) from Candida boidinii was found to be inactivated and unstable in the presence of high concentration (>50%) of the water soluble dimethylimidazolium dimethyl phosphate ([MMIm][Me₂PO₄]) ionic liquid. In order to circumvent this problem, the enzyme was chemically modified by cations usually present in ionic liquids: cholinium (1), hydroxyethyl-methylimidazolium (2) and hydroxypropyl-methylimidazolium (3) cations were activated with carbonyldiimidazole before being reacted with the FDH leading to a heterogeneous population of 6–7 biocatalysts. FDH modified by (1) or (3) led to 3–9 modifications while FDH modified by (2) led to 6 proteins presenting 7–12 grafted cations. Specific activity of the modified enzymes was decreased by a 2.5–3-fold factor (0.10–0.15 μmol min⁻¹ mg⁻¹) compared to the non-modified FDH (0.33 μmol min⁻¹ mg⁻¹) when assayed in carbonate buffer (pH 9.7, 25 mM). After modification, the FDH still present 0.06 μmol min⁻¹ mg⁻¹ in 70% [MMIm][Me₂PO₄] (v:v) (30–45% of their activity in aqueous buffer) while the native enzyme is inactive at this ionic liquid concentration, proving the efficiency of this strategy. The half-life of the modified enzyme is also increased by a 5-fold factor after modification by (1) (t_1/2 of 9 days) and by a 3-fold factor after modification by (2) or (3) (t_1/2 of 6 and 5 days respectively) in aqueous solution. When stored in 37.5% [MMIm][Me₂PO₄] (v:v), both modified and unmodified FDH have an increased half-life (t_1/2 of 6–9 days). This grafting strategy is found to be good methods to mimic and study the stabilizing effect of ionic liquids on enzymes.     

A new synthesis and an antiviral assessment of the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin

A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where fluorination occurred once the purine ring was present. Compound 3 was assayed versus a number of viruses. A favorable response was observed towards measles (IC₅₀ of 1.2 μg/mL in the neutral red assay and 14 μg/mL by the visual assay) but this was accompanied by cytotoxicity in the CV-1 host cells (21–36 μg/mL). Among the viruses unaffected by 3 were human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were inhibited by the 4′,4′-difluoro analog of 3 (that is, 2).