Prasad P. Kulkarni

Neutral Metal Complex in an Ionic Pocket: Synthesis, Physicochemical Properties and X-ray Structure of a Copper(II) Complex Containing Neutral as Well as Cationic Dafone Ligands and Dafonium Perchlorate

Abstract A neutral copper complex flanked by two protonated 4,5-diazafluoren-9-one (dafone, 1) ligands which are H-bonded with water molecules and perchlorate anions has been structurally and electrochemically characterized. The capped copper compound remains intact in solution, exhibiting a reversible Cu(II)/Cu(I) couple although undergoing a deformation along the Cu–N(2) axis and can serve as a good model of ionic pockets with metal active sites in some metalloproteins.

Comparative studies on copper(I) complexes: synthesis, X-ray crystallography and electrochemical properties of [CuI(dafone)nX] complexes (dafone=4,5-diaza-fluoren-9-one, X=Br, I, SCN)

Abstract The synthesis, X-ray structures and electrochemical properties of stable five-coordinate, trigonal-bipyramidal CuI complexes of dafone (4,5-diaza-fluoren-9-one) [Cu(dafone)2X] with X=Br (1) or I (2) as ancillary ligands are discussed. The thiocyanate-bridged polymeric CuI complex of dafone, [Cu(dafone)(SCN)]n (3), forms two-dimensional sheets in the crystal, held together by weak interactions involving the dafone ketone group, while the phenanthroline complex, [Cu(phen)(SCN)]n (4), a zigzag arrangement of the phen ligands leads to interchain π-stacking within the lattice. The electrochemical studies reveal that dafone stabilizes the CuI oxidation state more efficiently than phen due to its better π-acceptor ability as indicated by more positive redox potentials for the CuI/CuII couple.

Communication:: The first well characterized Fe (phen) Cl3 complex : structure of aquo mono(1,10-phenanthroline) iron (III) trichloride : [Fe (phen) Cl3 (H2O)]

Abstract The crystal structure of the neutralpseudo-octahedral mono phenanthroline iron (III) complex Fe (phen) Cl3H2O is reported which surprisingly is the first well-characterized Fe (phen) Cl3 complex (space group P1 a = 10224 (4) d b = 10603 (3) d c = 6628 (2) d alpha 10070 (2) °β = 10817 (2) °γ = 9206 (2) ° R = Rw = 0033) Of the three unidentate chloride ions two are coplanar with phenanthroline ligand while the third is out of plane and is trans to the water molecule The metal environment is distorted from regular octahedral due to the non-equivalent ligand donor set The N–Fe–N bite angle of 756° is compressed below right-angular with a corresponding opening of the other bond angles around the iron in this plane The Fe — Cl bonds are inequivalentranging from 225 to 235 d the axial Fe — Cl bond being elongated The axial aquo group is tilted towards the phenanthroline ringmaking an angle of 838° with N (1) and 818° with N (2) respectively Comparison with the Mn (III) analog yields the effect of changing from a high spin d 5 to a high spin d 4 center III) ; phenanthroline ; DNA intercalator.

Mass spectral studies reveal the structure of Aβ1-16-Cu2+ complex resembling ATCUN motif.

In Alzheimers disease, copper binds to amyloid beta (Aβ) peptide and generates oxidative stress. The coordination of histidine (His) residues to Cu(2+) is still uncertain. We studied Cu(2+) binding to Aβ1-16 peptide using the diethyl pyrocarbonate (DEPC) assay and mass spectrometry. Our results show that only one His is involved in Cu(2+) coordination, which is identified as His6 using mass spectral studies. Novel nickel displacement studies have further supported the proposal that the Cu(2+) binding site of Aβ1-16 peptide resembles the ATCUN motif of human serum albumin.

Solution Structure of Physiological Cu(His)2: Novel Considerations into Imidazole Coordination

A disagreement on the mode of histidine binding to copper and the structure of [Cu(2+)(His)(2)] in solution still exists. Spectroscopic data in solution support a six-coordinate species with N4O2 donor atoms, while X-ray crystallography reveals five-coordinate N(3)O(2) donor atoms. We modified [Cu(2+)(His)(2)] in solution using diethyl pyrocarbonate (DEPC) and monitored the products spectrophotometrically and by mass spectrometry. Our spectrophotometric study indicates the presence of a free imidazole in the [Cu(2+)(His)(2)] complex in solution. Mass spectral characterization of a DEPC-modified [Cu(2+)(His)(2)] complex yielded a peak at 587.8 amu corresponding to three DEPC adducts. Taken together, our data indicate that the [Cu(2+)(His)(2)] complex in solution exists as a neutral five-coordinate structure with N3O2 donor atoms.

Hemiprotonated dafone, a new cationic species. The novel di-dafonium iron(III) complex: [(dafone)2H]+[FeCl4]−

Abstract The reaction of dafone (4,5-diazafluoren-9-one, 1) and iron(III) chloride in concentrated hydrochloric acid medium yields an unusual complex containing hemiprotonated dafone, [(dafone)2H]+[FeCl4]−. The crystal structure reveals that two coordinating ligands share a single proton to form the new cation [(dafone)2H]+ while the accompanying tetrachloroferrate(III) anion stabilizes the ion pair. The [FeCl4]− anion is close to tetrahedral in geometry with four chloro ligands in the first coordination sphere which is only slightly affected by the interactions with the di-dafonium unit.

Fluorescent Copper Probe Inhibiting Aβ1–16-Copper(II)-Catalyzed Intracellular Reactive Oxygen Species Production

A variety of fluorescent probes are proposed to monitor the intracellular copper content. So far, none of the probes have been evaluated for their potential to inhibit copper-associated intracellular oxidative stress. Herein, we studied the ability of a fluorescent copper probe, OBEP-CS1, to inhibit intracellular oxidative stress associated with an amyloid β (Aβ) peptide-copper complex. The data showed that OBEP-CS1 completely inhibits the copper-catalyzed oxidation as well as decarboxylation/deamination of Aβ1-16. Moreover, the cell imaging experiments confirmed that OBEP-CS1 can inhibit Aβ-CuII-catalyzed reactive oxygen species production in SH-SY5Y cells. We also demonstrated that Aβ1-16 peptide can bind intracellular copper and thereby exert oxidative stress.

Cisplatin Inhibits the Formation of a Reactive Intermediate during Copper-Catalyzed Oxidation of Amyloid β Peptide

Cisplatin was studied for its effect on the copper-catalyzed oxidation of amyloid β (Aβ) peptide. The interaction of cisplatin with Aβ1-16 in the presence of Cu(II) was investigated using cyclic voltammetry and mass spectrometry. The positive shift in the E1/2 value of Aβ1-16-Cu(II) suggests that the interaction of cisplatin alters the copper-binding properties of Aβ1-16. The mass spectrometry data show complete inhibition of copper-catalyzed decarboxylation/deamination of the Asp1 residue of Aβ1-16, while there is a significant decrease in copper-catalyzed oxidation of Aβ1-16 in the presence of cisplatin. Overall, our results provide a novel mode by which cisplatin inhibits copper-catalyzed oxidation of Aβ. These findings may lead to the design of better platinum complexes to treat oxidative stress in Alzheimers disease and other related neurological disorders.

A Bimodal, Cationic, and Water-Soluble Calix[4]arene Conjugate: Design, Synthesis, Characterization, and Transfection of Red Fluorescent Protein Encoded Plasmid in Cancer Cells

A new bimodal fluorescent cationic calix[4]arene (L1) conjugate has been synthesized in multiple steps and well characterized by NMR and electrospray ionization-mass spectrometry (ESI-MS) techniques. L1 has been investigated for its DNA binding ability by various spectroscopy techniques like absorption, fluorescence, and circular dichroism (CD). The formation of L1-DNA complex has been confirmed by the gel electrophoresis in the presence of incremental concentration of L1. To visualize the packing of the plasmid (pBR322), detailed tapping mode atomic force microscopy study has been performed, which revealed blob-like structure of plasmid upon addition of the incremental amount of L1. Concentration dependent transfection ability of L1 has been established in MCF-7 cells by confocal microscopy by carrying the red fluorescent protein (RFP) encoded plasmid pCMV-tdTomato-N1 to emit both intrinsic fluorescence of L1 as well as that from RFP. All this has been possible in the absence of any adjuvant phospholipids (DOPE) that are commonly used as helper. Further transfection efficiency of L1 has been compared with the commercially available lipofectamine (LTX) in two cancer cell lines, MCF 7 and SH-SY5Y, and found that the L1 is as efficient as that of LTX. Hence, L1 is an efficient and effective cargo to transport genetic material into the cells.

Acetylcholinesterase and Aβ Aggregation Inhibition by Heterometallic Ruthenium(II)–Platinum(II) Polypyridyl Complexes

Two heteronuclear ruthenium(II)-platinum(II) complexes [Ru(bpy)2(BPIMBp)PtCl2]2+ (3) and [Ru(phen)2(BPIMBp)PtCl2]2+ (4), where bpy = 2,2-bipyridine, phen = 1,10-phenanthroline, and BPIMBp = 1,4-bis[(2-pyridin-2-yl)-1H-imidazol-1-ylmethyl]-1,1-biphenyl, have been designed and synthesized from their mononuclear precursors [Ru(bpy)2(BPIMBp)]2+ (1) and [Ru(phen)2(BPIMBp)]2+ (2) as multitarget molecules for Alzheimers disease (AD). The inclusion of the cis-PtCl2 moiety facilitates the covalent interaction of Ru(II) polypyridyl complexes with amyloid β (Aβ) peptide. These multifunctional complexes act as inhibitors of acetylcholinesterase (AChE), Aβ aggregation, and Cu-induced oxidative stress and protect neuronal cells against Aβ-toxicity. The study highlights the design of metal based anti-Alzheimers disease (AD) systems.