[Show abstract][Hide abstract] ABSTRACT: Reduction of carbon dioxide to products such as oxalate (C2O4(2-)) is an active area of research, as the process converts an environmental pollutant into more useful organic compounds. However, carbon dioxide reduction remains a major challenge. Here we demonstrate a three-step reaction sequence in which a copper complex converts carbon dioxide to oxalate under mild conditions. The copper(II) complex is reduced to copper(I) in solution, either electrochemically or using sodium ascorbate. The reduced complex selectively reacts with carbon dioxide from air and fixes it into oxalate, with the oxalate ion bridging between two copper atoms. The bound oxalate ion is released as oxalic acid on treatment with mineral acids, regenerating the original copper(II) complex. This completes the process for conversion of carbon dioxide into oxalate using a binuclear copper complex and a mild reducing agent.
[Show abstract][Hide abstract] ABSTRACT: A p-xylyl-based macrocycle L has been synthesized and its binding properties with halides have been investigated by 1 H NMR titrations, single crystal X-ray diffraction analysis, and density functional theory (DFT) calculations. As investigated by 1 H NMR titrations, the ligand preferentially binds a halide in a 1:2 binding mode, with the association constants (in log K 2) of 2.82, 2.70, 2.28, and 2.20 for fluoride, chloride, bromide, and iodide, respectively. The overall binding trend was found to be in the order of fluoride > chloride > bromide > iodide, reflecting that the binding strength correlates with the relative basicity and size of the respective halide. Crystallographic studies indicate that the ligand forms 1:2 complexes with chloride, bromide and iodide. In the chloride complex, the ligand is hexaprotonated and each chloride is held via three NH···Cl − bonds. The ligand is tetraprotonated for the other complexes, where each halide is H-bonded to two secondary ammonium NH + groups via NH···X − bonds. The results of DFT calculations performed on [H 6 L] 6+ at M062x/6-311G (d,p) level in both gas and solvent phases, suggest that the ligand binds halides with the binding energy in the order of F − > Cl − > Br − > I −
The Journal of Physical Chemistry A 12/2014; 119(2):383–394. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Graphical abstract
Left: Crystal structure of Pr1.33Pt4Ga10 showing Pr and Ga vacancies in the Pr2Ga3 plane. Right: Tunneling electron microscopy (TEM) image of Pr1.33Pt4Ga10. These vacancies have been studied using TEM and pair distribution function analysis. Magnetic measurements reveal that Pr3+ ions order ferrimagnetically below 7.8(2) K.
Journal of Solid State Chemistry 12/2014; 220:9–16. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pr1.33Pt4Ga10 single crystals are prepared from the elements using excess Ga as flux (alumina crucible in evacuated silica ampoule, 1150 °C, 4 h, 2; ≈10% yield).
[Show abstract][Hide abstract] ABSTRACT: New mononuclear amidine complexes, fac-[Re(CO)3(Me2bipy)(HNC(CH3)(pyppz))]BF4 [(4,4'-Me2bipy (1), 5,5'-Me2bipy (2), and 6,6'-Me2bipy (3)] (bipy = 2,2'-bipyridine), were synthesized by treating the parent fac-[Re(I)(CO)3(Me2bipy)(CH3CN)]BF4 complex with the C2-symmetrical amine 1-(4-pyridyl)piperazine (pyppzH). The axial amidine ligand has an exposed, highly basic pyridyl nitrogen. The reaction of complexes 1-3 with a B12 model, (py)Co(DH)2Cl (DH = monoanion of dimethylglyoxime), in CH2Cl2 yielded the respective dinuclear complexes, namely, fac-[Re(CO)3(Me2bipy)(μ-(HNC(CH3)(pyppz)))Co(DH)2Cl]BF4 [(4,4'-Me2bipy (4), 5,5'-Me2bipy (5), and 6,6'-Me2bipy (6)]. (1)H NMR spectroscopic analysis of all compounds and single-crystal X-ray crystallographic data for 2, 3, 5, and 6 established that the amidine had only the E configuration in both the solid and solution states and that the pyridyl group is bound to Co in 4-6. Comparison of the NMR spectra of 1-3 with spectra of 4-6 reveals an unusually large "wrong-way" upfield shift for the pyridyl H2/6 signal for 4-6. The wrong-way H2/6 shift of (4-Xpy)Co(DH)2Cl (4-Xpy = 4-substituted pyridine) complexes increased with increasing basicity of the 4-Xpy derivative, a finding attributed to the influence of the magnetic anisotropy of the cobalt center on the shifts of the (1)H NMR signals of the pyridyl protons closest to Co. Our method of employing a coordinate bond for conjugating the fac-[Re(I)(CO)3] core to a vitamin B12 model could be extended to natural B12 derivatives. Because B12 compounds are known to accumulate in cancer cells, such an approach is a very attractive method for the development of (99m)Tc and (186/188)Re radiopharmaceuticals for targeted tumor imaging and therapy.
[Show abstract][Hide abstract] ABSTRACT: Catalytic hydrogenation of dibenzyl 5-dipyrroketone-2,9-dicarboxylates followed by decarboxylative iodination affords a 2,9-diiododipyrroketone which gives a 2,5,9-trichlorodipyrromethene hydrochloride after nucleophilic addition/elimination, with adventitious chloride to replace the two iodide groups. Treatment with BF3.Et2O gives a 3,5,8-trichloro-BODIPY that readily undergoes regioselective Stille coupling at the 8-position, or homo/mixed couplings at the 3,8- or 3,5 and 8-positions. Stepwise and controlled replacement of the 3,5 and 8 chlorine atoms using Stille reagents results in formation of a completely unsymmetrical trisubstituted BODIPY. Several examples of unsymmetrical BODIPYs were synthesized and characterized using this methodology. Structure features of new BODIPYs are discussed within the context of 14 new X-ray structures, and photophysical parameters of all new BODIPY compounds are reported and discussed.
The Journal of Organic Chemistry 09/2014; · 4.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new binucleating tetraphosphine ligand, rac- and meso-(Et2P-1,2-C6H4)P(Ph)CH2(Ph)P(1,2-C6H4PEt2) (et,ph-P4-Ph), has been synthesized. Separation and purification of the ligand diastereomers have been accomplished via column chromatography. Ni2Cl4(et,ph-P4-Ph) complexes of both diastereomers have been prepared in high yield and crystallographically characterized.
[Show abstract][Hide abstract] ABSTRACT: The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies (ACTs) have been rendered less effective due to developing parasite resistance and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940's and 1960's that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure activity studies (SAR) and structure property studies (SPR) were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation for the quinolone series was carried out to downselect the most promising 4(1H)-quinolones 7, 62, 66 and 67 which possessed low nanomolar EC50s against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using P. berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.
Journal of Medicinal Chemistry 08/2014; · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A series of tri[(p-carboranylmethylthio)tetrafluorophenyl]porphyrin conjugates of linear and branched polyamines, glucose, arginine, tri(ethylene glycol), and peptide Tyr-D-Arg-Phe-β-Ala (TAPA) were synthesized. These conjugates were investigated for their BBB permeability in human hCMEC/D3 brain endothelial cells as model, and their cytotoxicity and uptake in human glioma T98G cells. For comparison purposes, a symmetric tetra[(p-carboranylmethylthio)tetrafluorophenyl]porphyrin was also synthesized and its crystal structure was obtained. All porphyrin conjugates show low dark cytotoxicity (IC50 > 400 μM) and low phototoxicity (IC50>100 μM at 1.5 J/cm2) toward T98G cells. All conjugates were efficiently taken up by T98G cells, particularly the cationic polyamine and arginine conjugates, and localized in multiple cell organelles, including the mitochondria and lysosomes. All compounds showed relatively low in vitro BBB permeability compared with lucifer yellow, probably due to their higher molecular weight, hydrophobicity and tendency for aggregation in solutions. Among this series, the branched polyamine and TAPA conjugates showed the highest permeability coefficients, while the glucose conjugate showed the least.
[Show abstract][Hide abstract] ABSTRACT: β-Nitrocorroles are potentially valuable platforms for the preparation of a wide range of more elaborated corrole derivatives possessing unique chemical functionalities and electronic properties. Here we report our results on the chemical manipulation of a copper 3-NO2-triarylcorrolate using different organic reactions, all involving the reduction of -NO2 to -NH2 at an early stage, followed by further transformations. By way of a β-acylated copper corrolate, a novel corrole derivative bearing an alkyl azide group on the peripheral positions was obtained and exploited in the Huisgen 1,3-dipolar cycloaddition.
[Show abstract][Hide abstract] ABSTRACT: The palladium-catalyzed ortho monobromination and iodination of single E or Z geometric isomers of
substituted diaryl ketoxime ethers [Ar1C(Ar2) = N–OCH3] have been accomplished in good yield
(64–82% isolated yield). A minor amount of di-ortho-halogenation side product is produced in this reaction
(0–10%). The aromatic ring that is halogenated is the one ‘trans’ to the OCH3 group, indicating that
there is no isomerization about the C@N bond during the reaction. Further, the site of functionalization is
presumably controlled by the lone pair electrons on nitrogen. This study is the first to demonstrate the
ability of the geometry of the oxime ether group to target the functionalization of only one aromatic ring
when there are two aromatic rings directly attached to the carbon of the C@N bond of the oxime ether.
Electron-withdrawing substituents on either ring decrease reaction rate and diminish the amount of
di-ortho-bromination side product.
[Show abstract][Hide abstract] ABSTRACT: (LaxCe1−x)1.33Pt4Ga10 (0 ⩽ x ⩽ 1), synthesized with excess Ga flux, crystallize in the P63/mmc space group, Z = 1, with lattice parameters a = b ∼ 4.3 and c ∼ 16.5 Å for the entire range of the solid solution. Single-crystal diffraction and electron microscopy methods show that La substitution within the solid solution does not lead to systematic decrease in unit cell dimensions. The crystal structure of (LaxCe1−x)1.33Pt4Ga10 (0 ⩽ x ⩽ 1) can be viewed as a combination of RE2Ga3 (A) and double Pt2Ga4 (B) layers stacked along the c axis in an ABAB sequence. Ce1.33Pt4Ga10 exhibits a large negative Weiss constant, θW = −87.2 K, but does not reveal any signature of magnetic ordering. An examination of zero-field-cooled and field-cooled magnetization curves and AC susceptibility at low temperatures excludes a possible formation of spin-glass state down to 1.8 K. These findings support an earlier suggestion that Ce1.33Pt4Ga10 might exhibit non-Fermi liquid behavior.
Journal of Alloys and Compounds 07/2014; 600:193–198. · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: DABCO (1,4-diazabicyclo[2.2.2]octane) catalyzed a multicomponent reaction using the starting precursor 2,3,4,9-tetrahydro-1H-carbazol-1-one, malononitrile, and aromatic/heteroaromatic aldehyde.
[Show abstract][Hide abstract] ABSTRACT: Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 µM). To facilitate synthetically feasible derivatives, an alternate core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 µM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72 and 73; IC50 values from 0.718 to 0.079 µM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59 and 65) bound to a multi-domain PARP-1 structure were obtained, providing insights into further development of these inhibitors.
Journal of Medicinal Chemistry 06/2014; · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing P. vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity in several mouse models, and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses (+)-(S)-PQ also showed more systemic toxicity to mice. In Beagle dogs (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg/day orally for 3 days, while the (-)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human glucose-6-phosphate dehydrogenase (G6PD) deficiency, it was also demonstrated that (-)-(R)-PQ was less hemolytic compared to (+)-(S)-PQ to the G6PD deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (-)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (-)-(R)-PQ may have a better safety margin than the racemate in human.
Antimicrobial Agents and Chemotherapy 06/2014; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brevianes are a family of bioactive meroterpenoids originally described in fungi of the family Penicillium. These compounds have attracted a great deal of interest not only because of their unusual skeleton, suggesting a mixed mevalonate and polyketide biogenetic pathway, and their unusual oxa-spiro ring fused to a α-pyrone, but also because of the bioactivities shown by many members of this family.
Pest Management Science 05/2014; · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A number of 1,2,4-oxadiazolone and mercapto nitro benzimidazole derivatives containing 1,2,4-oxadiazole and hydantoin moieties have been prepared, and their structures were identified by means of spectral/physical characteristics including X-ray diffraction data.