Mark W. Bezpalko’s research while affiliated with Villanova University and other places

A new thiosemicarbazone derivative ligand N-(4-chlorophenyl)-2-(pyridin-2-ylmethylene)hydra­zine-1-carbothioamide (HL) and its zinc(II) complex [ZnL2]·CH2Cl2 (1) are prepared and cha­racterized by elemental analysis, FTIR and 1H NMR spectroscopy, and single crystal X-ray diffraction (for 1). The X-ray analysis reveals that the zinc atom is octahedrally coordinated by two NpyNimineSthiolate-donor ligands with the mer form. The HL ligand is deprotonated during the complexation process through the thiol group. In the crystal network of 1, the N—H⋯S hydrogen bonds form R22(8) hydrogen bond motifs. In addition, the crystal network is more stabilized by π—π stacking and C—H⋯π interactions. The ability of complex 1 to interact with ten selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II, and B-DNA) is investigated by docking studies. The results show that in many cases, complex 1 can interact with proteins better than doxorubicin.

The pyran­opyran amide (2S,4aR,8aR)-6-oxo-2,4a,6,8a-tetra­hydro­pyrano[3,2-b]pyran-2-carboxamide, C9H9NO4, 3, was prepared by a chemoselective hydration of the corresponding nitrile, 2, using a heterogeneous catalytic method based on copper(II) supported on mol­ecular sieves, in the presence of acetaldoxime. Compound 3 belongs to a new class of pyran­opyrans that possess anti­bacterial and phytotoxic activity. Crystallographic analysis of 3 shows a bent structure for the cis-fused bicyclic pyran­opyran, similar to nitrile 2. Evidence of an intra­molecular hydrogen bond involving the amide group and ring oxygen was not observed; however, two separate inter­molecular hydrogen-bonding inter­actions were observed between the amide hydrogen atoms and adjacent carbonyl oxygen atoms along the b- and a-axis directions. The latter inter­action may also be supported by an inter­molecular C—H⋯O hydrogen bond. The lattice is filled out by close-packed layers of this hydrogen-bonded network along the c-axis direction, related from one to the next by a 21 screw axis.

The efficiency of various gold compounds containing bis(phosphino)ferrocene ligands for catalyzing ring-closing reactions was examined. Six commercially available bis(phosphino)ferrocene ligands: 1,1′-bis(ditert-butylphosphino)ferrocene (dtbpf), 1,1′-bis(diphenylphosphino)ferrocene (dppf), 1,1′-bis(dicylohexylphosphino)ferrocene (dcpf), 1,1′-bis(diiso-propylphosphino)ferrocene (dippf), 1-diphenylphosphino-1′-di-tert-butylphosphinoferrocene (dppdtbpf) and 1,1′-bis(5-methyl-2-furanylphosphino)ferrocene (dfurpf) were employed in this study. In addition to the previously reported [Au 2 Cl 2 (μ-PP)] (PP = dtbpf, dppf, dcpf, dippf or dppdtbpf) compounds, [Au 2 Cl 2 (μ-dfurpf)] was synthesized and characterized by NMR spectroscopy, cyclic voltammetry and X-ray crystallography. All of these gold compounds react with Na[BArF 24 ] (BArF 24 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) to remove a chloride and yield the cationic monochlorides, [Au 2 (μ-Cl)(μ-PP)] ⁺ . The effectiveness of the [Au 2 Cl 2 (μ-PP)] and [Au 2 (μ-Cl)(μ-PP)][BArF 24 ], either pre-formed or generated in situ, compounds for the catalytic intramolecular alkyne hydroalkoxylation of (Z)-3-methylpent-2-en-4-yn-1-ol was examined in CDCl 3 and toluene-d 8 . The ring-closing of N-(prop-2-yn-1-yl)benzamide was also examined and was efficiently carried out in toluene-d 8 using [Au 2 (μ-Cl)(μ-PP)][BArF 24 ] (PP = dtbpf, dppf, dcpf, dippf, dppdtbpf or dfurpf). In addition, [Au 2 Cl 2 (μ-dppe)] and [Au 2 (μ-Cl)(μ-dppe)][BArF 24 ] were examined as catalysts for these ring-closing reactions in order to determine if the ferrocene backbone of the bis(phosphino)ferrocene ligands was important for catalysis.

Twenty‐one mono‐ and biscationic quaternary ammonium amphiphiles (monoQACs and bisQACs) were rapidly prepared in order to investigate the effects of rigidity of a diamine core structure on antiseptic activity. As anticipated, the bioactivity against a panel of six bacteria including methicillin‐resistant Staphylococcus aureus (MRSA) strains was strong for bisQAC structures, and is clearly correlated with the length of non‐polar side chains. Modest advantages were noted for amide‐containing side chains, as compared with straight‐chained alkyl substituents. Surprisingly, antiseptics with more rigidly disposed side chains, such as those in DABCO‐12,12, showed the highest level of antimicrobial activity, with single‐digit MIC values or better against the entire bacterial panel, including sub‐micromolar activity against an MRSA strain.

The phytotoxin diplopyrone is considered to be the main phytotoxin in a fungus that is responsible for cork oak decline. A carbohydrate-based synthesis of the enantiomer of the structure proposed for diplopyrone has been developed from 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose, a commercially available derivative of D-galactose. Key steps in the synthesis are a highly stereoselective pyranose chain-extension based on methyltitanium, preparation of a vinyl glycoside via Isobe C-alkynylation-rearrangment/reduction, and RCM (ring-closing methathesis)-based pyranopyran construction. Crystallographic and NMR analysis confirms an earlier report that the structure originally proposed for diplopyrone may require revision. Structural analogs were prepared for biological evaluation, the most promising being a pyranopyran nitrile that was synthesized from tri-O-acetyl-D-galactal by Ferrier cyanoglycosidation, Wittig chain extension, and lactonization. Biological assays revealed potent antibacterial activity for the nitrile analog against common bacterial pathogens E. ictaluri and F. columnare that cause enteric septicemia (ESC) and columnaris disease, respectively, in catfish. The IC50 value of 0.002 against E. ictaluri indicates approximately 100 times greater potency than the antibiotic florfenicol used commercially for this disease. Phytotoxic activity for all three target compounds against duckweed was also observed. The antibiotic and phytotoxic activities of the new pyranopyrans synthesized in this study demonstrate the potential of such compounds as antibiotics and herbicides.

Neutral bivalent copper and nickel bis(thiosemicarbazone) complexes bearing the methoxy and bromine substituents on the dialdehyde-backbone of the ligand have been synthesized. All of them have been characterized by spectroscopic methods and in two cases by X-ray crystallography. Upon formation of these complexes, the each two bis(thiosemicarbazone) arms is deprotonated, acting as dianionic, tetradentate N2S2 ligands. The geometrical distortion from square planar in the copper complex is very greater than the nickel complex. Cyclic voltammetry studies of Cu(II) and Ni(II) complexes in DMF show that all complexes are able to stabilize low oxidation states of Cu(I) and Ni(I). The introduction of different substitutions on the aromatic ring attached to the imine carbon led to two consequences. First, The E1/2 values for the CuI/CuII and NiI/NiII redox couples were cathodically shifted in comparison with the unsubstituted analog. Second, the copper complexes underwent a quasi-reversible one-electron oxidation (CuII/CuIII).

The synthesis and full characterization of a series of neutral ligand α-diimine complexes of aluminum are reported. The compounds [Al(LAr)2Cl2)][AlCl4] [LAr= N, N'-bis(4-R-C6H4)-2,3-dimethyl-1,4-diazabutadiene] are structurally analogous, as determined by multinuclear NMR spectroscopy and solid-state X-ray diffraction, across a range of electron-donating [R = Me (2),tBu (3), OMe (4), and NMe2(5)] and electron-withdrawing [R = Cl (6), CF3(7), and NO2(8)] substituents in the aryl side arm of the ligand. UV-vis absorption spectroscopy and electrochemistry were used to access the optical and electrochemical properties, respectively, of the complexes. Both sets of properties are shown to be dependent on the R substituent. Density functional theory calculations performed on the [Al(LPh)2Cl2)][AlCl4] complex (1) indicate primarily ligand-based frontier orbitals and were used to help support our discussion of both the spectral and electrochemical data. We also report the reaction of the LPhligand with both AlBr3and AlI3and demonstrate a different reactivity profile for the heavier halide relative to the lighter members of the group.

The synthesis of two 2,3-dideoxy glycosyl cyanides was carried out by the Ferrier reaction of O-peracetylated D-glucal with trimethylsilyl cyanide and Lewis acid catalysts, chemoselective reduction of the double bond in the products, and deacylation. X-ray crystallographic analysis of the products revealed features consistent with the anomeric effect of the cyano group, similar to other glycosyl cyanides that are included for comparison. Computational studies were carried out to evaluate the energies and geometrical parameters of conformations in which the cyano group is axial and equatorial in both model and synthesized compounds.

The ligand 1,1'-bis(diphenylphosphino)ferrocene (dppf) is commonly employed in a variety of catalytic systems. There are a variety of coordination modes known for dppf, the least studied being the κ(3) coordination mode, in which both phosphorus atoms and the iron atom of dppf interact with another metal center. One such compound is the previously reported [Pd(κ(3)-dppf)(PPh3)](2+). A series of related compounds, [Pd(κ(3)-dppf)(P(p-C6H4R)3)](2+) (R = OCH3, CH3, F and CF3), has been synthesized and characterized. The X-ray crystal structure of [Pd(dppf)(P(p-C6H4F)3)][BF4]2 was determined. Electrochemical and computational studies indicate that the electron donor ability of the P(p-C6H4R)3 ligands influences the properties of these compounds. Substitution reactions of the P(p-C6H4R)3 ligands have been examined, and, in general, the more electron donating P(p-C6H4R)3 ligands completely replace the less electron donating ones. The kinetics of the reaction of [Pd(κ(3)-dppf)(P(p-C6H4F)3)](2+) with P(p-C6H4OCH3)3 indicate that the reaction proceeds through a dissociative mechanism, contrary to the associative substitutions prevalent in square planar palladium(ii) chemistry.