A Doppel α‐Helix Peptide Fragment Mimics the Copper(II) Interactions with the Whole Protein

The doppel protein (Dpl) is the first homologue of the prion protein (PrP^C) to be discovered; it is overexpressed in transgenic mice that lack the prion gene, resulting in neurotoxicity. The whole prion protein is able to inhibit Dpl neurotoxicity, and its N‐terminal domain is the determinant part of the protein function. This region represents the main copper(II) binding site of PrP^C. Dpl is able to bind at least one copper ion, and the specific metal‐binding site has been identified as the histidine residue at the beginning of the third helical region. However, a reliable characterization of copper(II) coordination features has not been reported. In a previous paper, we studied the copper(II) interaction with a peptide that encompasses only the loop region potentially involved in metal binding. Nevertheless, we did not find a complete match between the EPR spectroscopic parameters of the copper(II) complexes formed with the synthesized peptide and those reported for the copper(II) binding sites of the whole protein. Herein, the synthesis of the human Dpl peptide fragment hDpl(122–139) (Ac‐KPDNKLHQQVLWRLVQEL‐NH₂) and its copper(II) complex species are reported. This peptide encompasses the third α helix and part of the loop linking the second and the third helix of human doppel protein. The single‐point‐mutated peptide, hDpl(122–139)D124N, in which aspartate 124 replaces an asparagine residue, was also synthesized. This peptide was used to highlight the role of the carboxylate group on both the conformation preference of the Dpl fragment and its copper(II) coordination features. NMR spectroscopic measurements show that the hDpl(122–139) peptide fragment is in the prevailing α‐helix conformation. It is localized within the 127–137 amino acid residue region that represents a reliable conformational mimic of the related protein domain. A comparison with the single‐point‐mutated hDpl(122–139)D124N reveals the significant role played by the aspartic residue in addressing the peptide conformation towards a helical structure. It is further confirmed by CD measurements. Potentiometric titrations were carried out in aqueous solutions to obtain the stability constant values of the species formed by copper(II) with the hDpl peptides. Spectroscopic studies (EPR, NMR, CD, UV/Vis) were performed to characterize the coordination environments of the different metal complexes. The EPR parameters of the copper(II) complexes with hDpl(122–139) match those of the previously reported copper(II) binding sites of the whole hDpl. Addition of the copper(II) ion to the peptide fragment does not alter the helical conformation of hDpl(122–139), as shown by CD spectra in the far‐UV region. The aspartate‐driven preorganized secondary structure is not significantly modified by the involvement of Asp124 in the copper(II) complex species that form in the physiological pH range. To elaborate on the potential role of copper(II) in the recently reported interaction between the PrP^C and Dpl, the affinity of the copper(II) complexes towards the prion N terminus domain and the binding site of Dpl was reported.     

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

Prion diseases are a group of neurodegenerative diseases based on the conformational conversion of the normal form of the prion protein (PrP^C) to the disease‐related scrapie isoform (PrP^Sc). Copper(II) coordination to PrP^C has attracted considerable interest for almost 20 years, mainly due to the possibility that such an interaction would be an important event for the physiological function of PrP^C. In this work, we report the copper(II) coordination features of the peptide fragment Ac(PEG₁₁)₃PrP(60‐114) [Ac=acetyl] as a model for the whole N‐terminus of the PrP^C metal‐binding domain. We studied the complexation properties of the peptide by means of potentiometric, UV/Vis, circular dichroism and electrospray ionisation mass spectrometry techniques. The results revealed that the preferred histidyl binding sites largely depend on the pH and copper(II)/peptide ratio. Formation of macrochelate species occurs up to a 2:1 metal/peptide ratio in the physiological pH range and simultaneously involves the histidyl residues present both inside and outside the octarepeat domain. However, at increased copper(II)/peptide ratios amide‐bound species form, especially within the octarepeat domain. On the contrary, at basic pH the amide‐bound species predominate at any copper/peptide ratio and are formed preferably with the binding sites of His96 and His111, which is similar to the metal‐binding‐affinity order observed in our previous studies.     

New Insight in Copper‐Ion Binding to Human Islet Amyloid: The Contribution of Metal‐Complex Speciation To Reveal the Polypeptide Toxicity

Type‐2 diabetes (T2D) is considered to be a potential threat on a global level. Recently, T2D has been listed as a misfolding disease, such as Alzheimer's and Parkinson's diseases. Human islet amyloid polypeptide (hIAPP) is a molecule cosecreted in pancreatic β cells and represents the main constituent of an aggregated amyloid found in individuals affected by T2D. The trace‐element serum level is significantly influenced during the development of diabetes. In particular, the dys‐homeostasis of Cu²⁺ ions may adversely affect the course of the disease. Conflicting results have been reported on the protective role played by complex species formed by Cu²⁺ ions with hIAPP or its peptide fragments in vitro. The histidine (His) residue at position 18 represents the main binding site for the metal ion, but contrasting results have been reported on other residues involved in metal‐ion coordination, in particular those toward the N or C terminus. Sequences that encompass regions 17–29 and 14–22 were used to discriminate between the two models of the hIAPP coordination mode. Due to poor solubility in water, poly(ethylene glycol) (PEG) derivatives were synthesized. A peptide fragment that encompasses the 17–29 region of rat amylin (rIAPP) in which the arginine residue at position 18 was substituted by a histidine residue was also obtained to assess that the PEG moiety does not alter the peptide secondary structure. The complex species formed by Cu²⁺ ions with Ac‐PEG‐hIAPP(17–29)‐NH₂, Ac‐rIAPP(17–29)R18H‐NH₂, and Ac‐PEG‐hIAPP(14–22)‐NH₂ were studied by using potentiometric titrations coupled with spectroscopic methods (UV/Vis, circular dichroism, and EPR). The combined thermodynamic and spectroscopic approach allowed us to demonstrate that hIAPP is able to bind Cu²⁺ ions starting from the His18 imidazole nitrogen atom toward the N‐terminus domain. The stability constants of copper(II) complexes with Ac‐PEG‐hIAPP(14–22)‐NH₂ were used to simulate the different experimental conditions under which aggregate formation and oxidative stress of hIAPP has been reported. Speciation unveils: 1) the protective role played by increased amounts of Cu²⁺ ions on the hIAPP fibrillary aggregation, 2) the effect of adventitious trace amounts of Cu²⁺ ions present in phosphate‐buffered saline (PBS), and 3) a reducing fluorogenic probe on H₂O₂ production attributed to the polypeptide alone.     

Coordination Behavior of N‐Donor Schiff Base Derived from 2‐Benzoylpyridine Toward Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), and Cr(III) Metal Ions: Synthesis,Spectroscopic and Thermal Studies,and Biological Activity

A new Schiff base was prepared from the reaction of 4,4′‐methylenedianiline with 2‐benzoylpyridine in 1:2 molar ratio, as well as its different metal chelates. The structures of the ligand and its metal complexes were studied by elemental analyses, spectroscopic methods (infrared [IR ], ultraviolet–visible [UV –vis], ¹H nuclear magnetic resonance [NMR ], electron spin resonance [ESR ]), magnetic moment measurements, and thermal studies. The ligand acts as tetradentate moiety in all complexes. Octahedral geometry was suggested for Mn(II ), Cu(II ), Cr(III ), and Zn(II ) chloride complexes and pentacoordinated structure and square planar geometry for Co(II ), Ni(II ), Cu(NO₃ )₂, CuBr₂ , and Pd(II ) complexes. ESR spectra of copper(II ) complexes ( 4 )–( 6 ) at room temperature display rhombic symmetry for complex ( 4 ) and axial type symmetry for complexes ( 5 ) and ( 6 ), indicating ground state for Cu(II ) complexes. The derivative thermogravimetric (DTG ) curves of the ligand and its metal complexes were analyzed by using the rate equation to calculate the thermodynamic and kinetic parameters, which indicated strong binding of the ligand with the metal ion in some complexes. Also, some of these compounds were screened to establish their potential as anticancer agents against the human hepatic cell line Hep‐G₂ . The obtained IC₅₀ value of the copper(II ) bromide complex (4.34 µg/mL ) is the highest among the compounds studied.     

Synthesis,spectroscopic, thermal properties,Calf thymus DNA binding and quantum chemical studies of M(II) complexes

A new series of transition metal complexes of Cu(II), Co(II), Ni(II), Mn(II) and Cd(II) were prepared from the ligand of 5‐(4‐benzenesulfonic acid azo)‐2‐thioxo‐4‐thiazolidinone (H₂L). The M(II) complexes were structurally elucidated by elemental analysis, infrared spectra, spectral studies, thermal analysis, magnetic measurements and X‐ray diffraction analysis. Elemental analysis and IR result suggested the ligand was bonded to the metal ions in monobasic/neutral bidentate through the nitrogen atom of the hydrazone group and oxygen atom of carbonyl group. The bond length, bond angle, HOMO, LUMO and quantum chemical parameters were calculated to confirm the geometry of the ligand and the M(II) complexes. In vitro antimicrobial behavior of ligand (H₂L) and its M(II) complexes (1‐5) was screened with targeted bacterial and fungal strains. Spectroscopic (UV‐vis) technique was employed in order to study the binding mode and binding strength of the ligand (H₂L) and its M(II) complexes to Calf thymus DNA (CT‐DNA). Intercalation is the most possible mode of interaction of the ligand (H₂L) and its M(II) complexes with CT‐DNA and the determined binding constants. Molecular docking was used to predict the binding between the starts (4‐aminobenzenesulfonic acid (start 1) and 2‐thioxo‐4‐thiazolidinone (start 2)) and tautomers (A‐C) of ligand (H₂L) with the receptors of prostate cancer mutant (PDB code: 2Q7K) and breast cancer mutant (PDB code: 3HB5).     

Homo‐ and heteropolynuclear copper(II) complexes containing a new diimine–dioxime ligand and 1,10‐phenanthroline: synthesis,characterization, solvent‐extraction studies,catalase‐like functions and DNA cleavage abilities

A series of homo‐, heterodinuclear and homotrinuclear copper(II) complexes containing a new Schiff base ligand and 1,10‐phenanthroline were synthesized. Based on results of elemental analyses, FTIR, ¹H‐ and ¹³C‐NMR spectra, conductivity measurements and magnetic susceptibility measurements, the complexes had general compositions {[Cu(L)(H₂O)M(phen)₂](ClO₄)₂ [M = Cu(II), Mn(II), Co(II)]} and {[Cu₃(L)₂(H₂O)₂](ClO₄)₂}. The metal:L:phen ratio is 2:1:2 for the dinuclear copper(II) complexes and the metal:L ratio was 3:2 for the trinuclear copper(II) complex. The liquid–liquid extraction of various transition metal cations [Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II), Hg(II)] from the aqueous phase to the organic phase was carried out using the diimine–dioxime ligand. It was concluded that the ligand can effectively be used in solvent extraction of copper(II) from the aqueous phase to the organic phase. Furthermore, catalytic activitiy of the complexes for the disproportionation of hydrogen peroxide was also investigated in the presence of imidazole. Dinuclear copper(II)–manganese(II) complex has some similarity to manganese catalase in structure and activity. The interaction between these complexes and DNA has also been investigated by agarose gel electrophoresis; we found that the homo‐ and heterodinuclear copper complexes can cleave supercoiled pBR322 DNA to nicked and linear forms in the presence of H₂O₂. Copyright © 2009 John Wiley & Sons, Ltd.     

2,6-Diacetyl- and 2,6-diformylpyridine bis(N4-substituted thiosemicarbazones) and their copper(II) and nickel(II) complexes

2,6-Diformylpyridine bis(N4-methylthiosemicarbazone) and bis(N4-dimethylthiosemicarbazone), H₂2,6Fo4M and H₂2,6Fo4DM, respectively, and 2,6-diacetylpyridine bis(N4-methylthiosemicarbazone) and bis(N4-dimethylthiosemicarbazone), H₂2,6Ac4M and H₂2,6Ac4DM, and their copper(II) and nickel(II) complexes have been synthesized. The ¹H-n.m.r. spectra of the free bis(thiosemicarbazones) show that, most often, one of the thiosemicarbazone moieties is hydrogen bonded to the pyridine nitrogen, and in [²H₆]-DMSO there is interaction with solvent oxygen. Golden yellow H₂2,6Ac4DM has a bifurcated hydrogen bonding interaction by one of the thiosemicarbazone moieties resulting in conjugation. Coordination to copper(II) and nickel(II) centers is via the pyridine nitrogen, amine nitrogen and thiolato sulfur and most of the complexes formed are polynuclear with thiosemicarbazone moieties from the same ligand coordinating to different metal centers.     

Synthesis and structural studies of (2E,3E)-3-[(6-{[(1E,2E)-2-(hydroxyimino)-1-methylpropylidene]amino}pyridin-2-yl)imino]butan-2-one oxime, ligand and its mono-, di- and trinuclear copper(II) complexes

A new dioxime ligand, (2E,3E)-3-[(6-{[(1E,2E)-2-(hydroxyimino)-1-methylpropylidene]amino}-pyridin-2-yl)imino]butan-2-one oxime, (H₂Pymdo) (3) has been synthesized in H₂O by reacting 2,3-butenedione monoxime (2) with 2,6-diaminopyridine. Mono-, di- and tri-nuclear copper(II) complexes of the dioxime ligand (H₂Pymdo) and/or 1,10-phenanthroline have been prepared. The dioxime ligand (H₂Pymdo) and its copper(II) complexes were characterized by ¹H-n.m.r., ¹³C-n.m.r. and elemental analyses, magnetic moments, i.r. and mass spectral studies. The mononuclear copper(II) complex of H₂Pymdo was found to have a 1:1 metal:ligand ratio. Elemental analyses, stoichiometric and spectroscopic data of the metal complexes indicated that the metal ions are coordinated to the oxime and imine nitrogen atoms (C=N). In the dinuclear complexes, in which the first Cu(II) ion was complexed with nitrogen atoms of the oxime and imine groups, the second Cu(II) ion is ligated with dianionic oxygen atoms of the oxime groups and are linked to the 1,10-phenanthroline nitrogen atoms. The trinuclear copper(II) complex (6) was formed by coordination of the third Cu(II) ion with dianionic oxygen atoms of each of two molecules of the mononuclear copper(II) complexes. The data support the proposed structure of H₂Pymdo and its Cu(II) complexes.     

Syntheses,characterization and biological studies of zinc(II), copper(II) and cobalt(II) complexes with Schiff base ligand derived from 2‐hydroxy‐1‐naphthaldehyde and selenomethionine

Novel zinc(II), copper(II), and cobalt(II) complexes of the Schiff base derived from 2‐hydroxy‐1‐naphthaldehyde and D, L ‐selenomethionine were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, magnetic measurements and powder XRD. The analytical data showed the composition of the metal complex to be ML(H₂O), where L is the Schiff base ligand and M = Co(II), Cu(II) and Zn(II). IR results confirmed the tridentate binding of the Schiff base ligand involving azomethine nitrogen, naphthol oxygen and carboxylato oxygen atoms. ¹H NMR spectral data of lithium salt of the Schiff base ligand [Li(HL)] and ZnL(H₂O) agreed with the proposed structures. The conductivity values of complexes between 12.50 and 15.45 S cm² mol^?1 in DMF suggested the presence of non‐electrolyte species. The powder XRD studies indicated that Co(II) complex is amorphous, whereas Cu(II) and Zn(II) complexes are crystalline. The results of antibacterial and antifungal screening studies indicated that Li(HL) and its metal complexes are active, but CuL(H₂O) is most active among them. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis,characterization, fluorescence and redox features of new <Emphasis Type="Italic">vic</Emphasis>-dioxime ligand bearing pyrene and its metal complexes

A new vic-dioxime ligand, N,N′-bis(aminopyreneglyoxime) (LH₂), and its copper(II), nickel(II) and cobalt(II) metal complexes were synthesized and characterized by elemental analyses, IR, UVVIS and ¹H and ¹³C NMR spectra (for the ligand). Mononuclear complexes were synthesized by a reaction of ligand (LH₂) and salts of Co(II), Ni(II), and Cu(II) in ethanol. The complexes have the metal-ligand ratio of 1: 2 and metals are coordinated by N,N′ atoms of vicinal dioximes. The ligand acts in a polydentate fashion bending through nitrogen atoms in the presence of a base, as do most vic-dioximes. Detection of a H-bonding in the Co(II), Ni(II), and Cu(II) complexes by IR revealed the square-planar MN₄ coordination of mononuclear complexes. Fluorescent properties of the ligand and its complexes arise from pyrene units conjugated with a vic-dioxime moiety. Fluorescence emission spectra of the ligand showed a drastic decrease in its fluorescence intensity upon metal binding. The electrochemical properties of the complexes were studied by the cyclic voltammetry technique. The nickel complex displayed an irreversible oxidation process while the copper complex exhibited a quasi-reversible oxidation and reduction processes based on the copper Cu(II)/Cu(III) and Cu(II)/Cu(I) couples, respectively.     

Synthesis,characterization and in vitro biological activity of cobalt(II), copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and D,L‐selenomethionine

New cobalt(II), copper(II) and zinc(II) complexes of Schiff base derived from D,L ‐selenomethionine and salicylaldehyde were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, magnetic measurements and biological activity. The analytical data showed that the Schiff base ligand acts as tridentate towards divalent metal ions (cobalt, copper, zinc) via the azomethine‐N, carboxylate oxygen and phenolato oxygen by a stoichiometric reaction of M:L (1:1) to form metal complexes [ML(H₂O)], where L is the Schiff base ligand derived from D,L ‐selenomethionine and salicylaldehyde and M = Co(II), Cu(II) and Zn(II). ¹H NMR spectral data of the ligand and Zn(II) complex agree with proposed structures. The conductivity values between 12.87 and 15.63 S cm² mol^?1 in DMF imply the presence of non‐electrolyte species. Antibacterial and antifungal results indicate that the metal complexes are more active than the ligand. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and Biological Evaluation of some 3d Metal Complexes with a Novel Heterocyclic Schiff Base

A heterocyclic Schiff base was prepared by condensing 3‐acetylcoumarin with 2‐amino‐3‐carboxyethyl‐4,5,6,7‐tetrahydrobenzo[b ]thiophene. Such Schiff bases derived from two different heterocyclic moieties are rare and expected to have properties surpassing those of either of the parent compounds in effectiveness of complex formation and biological activities. This ligand formed a series of complexes with manganese(II), cobalt(II), nickel(II), copper(II), and zinc(II) ions. The ligand and the metal complexes were characterized by various physicochemical and spectral studies. These included elemental analysis, molar conductance, magnetic susceptibility, as well as UV–vis, IR, ¹H NMR, ¹³C NMR, and ESR spectral studies. The ESR spectral data adequately supported the covalent nature of the metal–ligand bonds. The ligand possessed a hexagonal crystal structure, but on complexation the crystallinity was lost. The fluorescence spectra of the ligand and its metal complexes in DMSO were also recorded. The ligand and the metal complexes were screened for their antimicrobial activities, and it was observed that the metal complexes are more active than the ligand. The α‐amylase inhibitory activity and the DNA cleavage activity of the ligand and the metal complexes were also examined. in vitro antitumor activity of the copper(II) complex was assayed against human cervical carcinoma cells (HeLa cell line), showing that the complex exhibited promising antitumor activity on the HeLa cell line.     

New insights into the metal ion–peptide hydroxamate interactions: Metal complexes of primary hydroxamic acid derivatives of common dipeptides in aqueous solution

Complex formation of primary dipeptide hydroxamic acids, L-Ala-L-AlaNHOH and L-Ala-L-SerNHOH, as well as the corresponding Z-protected ones, Z-L-Ala-L-AlaNHOH and Z-L-Ala-L-SerNHOH (Z = benzyloxycarbonyl), with iron(III), aluminium(III), nickel(II), copper(II) and zinc(II) was studied in aqueous solution by pH-potentiometric and spectroscopic (UV–Vis, EPR, CD, ¹H NMR) methods. The exclusive formation of [O,O] chelated hydroxamate complexes was found with iron(III) and aluminium(III) with all the ligands. Formation of linkage isomers with the involvement of either [O,O] hydroxamate or [NH₂,CO] chelates was detected both in the zinc(II)-L-Ala-L-AlaNHOH and -L-Ala-L-SerNHOH systems. Upon increasing the pH, none of these chelating sets are capable of preventing the hydrolysis of the metal ion. The formation of stable complexes was found in the nickel(II) and copper(II) systems above pH ∼ 6 with a [NH₂, N_amide, N_hydrox.] binding mode after deprotonation and coordination of the peptide amide and the hydroxamate group. With an excess of copper(II), the formation of trinuclear [Cu₃H_xL₂]^x+4 type (x = −4 to −6) complexes as the major species was also detected. Blocking the terminal amino group in the Z-protected ligands results in a dramatic decrease of the nickel(II) and zinc(II) binding strengths, and insoluble complexes with copper(II). No indication was found for the role of the hydroxyl group of the serine moiety in metal ion binding.     

Transition metal complexes of acetamidomalondihydroxamate: synthesis,spectral, thermal and electrochemical studies

Acetamidomalondihydroxamate (K₂AcAMDH) and its manganese(II), iron(II), cobalt(II), nickel(II), copper(II) and zinc(II) complexes were synthesized and characterized by elemental analysis, UV–VIS, IR and magnetic susceptibility. The pK _a1 and pK _a2 values of the dihydroxamic acid in aqueous solution were found to be 8.0?±?0.1 and 9.7?±?0.1. The dihydroxamate anion AcAMDH behaves as a tetradentate bridging ligand through both hydroxamate groups, forming complexes with a metal to ligand ratio of 1?:?1 in the solid state. The FTIR spectra and thermal decompositions of the ligand and its metal complexes were recorded. The redox behavior of the complexes was investigated in aqueous solution by square wave voltammetry and cyclic voltammetry at neutral pH. In contrast to the solid state, in solution the copper(II) and zinc(II) ions form stable complex species with a metal to ligand ratio of 1?:?2. The iron(II) and nickel(II) complexes show a two-electron irreversible reduction behavior, while the copper(II) and zinc(II) complexes undergo reversible electrode reactions. The stability constants of the complexes were determined by square wave voltammetry.     

The Coordination of NiII and CuII Ions to the Polyhistidyl Motif of Hpn Protein: Is It as Strong as We Think?

Hpn, one of Helicobacter pylori′s nickel‐accessory proteins, is an amazingly peculiar protein: Almost half of its sequence consists of polyhistidyl (poly‐His) residues. Herein, we try to understand the origin of this naturally occurring sequence, thereby shedding some light on the bioinorganic chemistry of Hpn′s numerous poly‐His repeats. By using potentiometric, mass spectrometric, and various spectroscopic techniques, we studied the Ni^II‐ and Cu^II complexes of the wild‐type Ac‐THHHHYHGG‐NH₂ fragment of Hpn and of its six analogues, in which consecutive residues (His or Tyr) were replaced by Ala (Ala‐substitution or Ala‐scan approaches), thereby resulting in Ac‐TAHHHYHGG‐NH₂, Ac‐THAHHYHGG‐NH₂, Ac‐THHAHYHGG‐NH₂, Ac‐THHHAYHGG‐NH₂, Ac‐THHHHAHGG‐NH₂, and Ac‐THHHHYAGG‐NH₂ peptides. We found that the His4 residue is critical for both Ni^II‐ and Cu^II‐ion binding and the effectiveness of binding varies even if the substituted amino acid does not take part in the direct binding interactions.     

Investigation of DNA Binding Interaction of Newly Synthesized Nickel(II) and Palladium(II) Complexes Containing Ferrocenyl Schiff Base Ligand

New complexes of nickel(II) and palladium(II) were synthesized using the ferrocenyl imine ligand, which was formed by the condensation of 2‐aminothiophenol and acetylferrocene. This bidentate Schiff base ligand was coordinated to the metal ions through the NS donor atoms. Monomeric complexes of nickel(II) and palladium(II) were synthesized by the reactions of the Schiff base ligand with nickel(II) and palladium(II) chloride in a 2:1 M ratio. In these complexes, the thiol group was deprotonated and coordinated to the metals. The molar conductivity values of the complexes in DMSO showed the presence of non‐electrolyte species. The fluorescence characteristics of the Schiff base ligand and its complexes were studied in DMSO. The synthesized complexes were characterized by FT‐IR, ¹H NMR, UV–vis spectroscopy, elemental analysis, and conductometry. Furthermore, the binding interactions of the complexes with DNA were investigated by electronic absorption spectroscopy, and the intrinsic binding constant (K _b) was calculated. Moreover, viscosity and melting temperature (T _m) were investigated in order to further explore the nature of interactions between the complexes and DNA.     

Green synthesis of biologically active transition metal nanoparticles containing novel Schiff base via catalyst free hydrothermal reaction: Structural,biological and morphology study

Novel cobalt, nickel and copper complexes were synthesized by regular reflux method and nano sized Co(II), Ni(II) and Cu(II) metal complexes were synthesized by a facile hydrothermal method using green solvent at various temperatures without the addition of any capping agent. The structural characterization was done by magnetic susceptibility, molar conductance, elemental analysis, thermal analysis, FT‐IR, ¹H NMR, ¹³C NMR, ESI mass, UV–Visible analysis. The morphology and size of the nano metal complexes were determined using FE‐Scanning electron microscopy, powder X‐ray diffraction data and atomic force microscopic techniques. All the spectral and analytical results reveal 1:2 metal to ligand ratios having [ML₂(H₂O)₂] stoichiometry, here M=Co(II), Ni(II) and Cu(II), L=deprotonated ligand. The non‐electrolytic nature of the compound was confirmed by molar conductance experiment. The synthesized Schiff base and its metal complexes (7, 8 and 9) were tested for their biological activity. All the tested compounds exhibit decent anticancer and DNA cleavage activity and copper complex shows better activity results than other tested compounds.     

Biomolecular docking,antimicrobial and cytotoxic studies on new bidentate schiff base ligand derived metal (II) complexes

Three new metal complexes [Cu(L)₂] (1), [Co(L)₂] (2) and [Zn(L)₂] (3) have been prepared by the reaction of hydrated salts of metal (II) acetate with new Schiff base ligand HL, [2‐((4‐(dimethylamino)phenylimino)methyl)‐4,6‐di‐t‐butylphenol] and characterized by different physico‐chemical analyses such as elemental analysis, single XRD, ¹H NMR, FTIR and UV–Vis spectroscopic techniques. Their biomolecular docking, antimicrobial and cytotoxicity studies have also been demonstrated. The proposed structure of Schiff base ligand HL and complex 2 are confirmed by Single crystal X‐ray crystallography study. This analysis revealed that metal (II) complexes remain in distorted tetrahedral coordination environments. The electronic properties such as HOMO and LUMO energies are carried out by gaseous phase DFT/B3LYP calculations using Gaussian 09 program. Complex 1 showed a good binding propensity to the DNA and HSA, during the assessment of docking studies. Schiff base ligand HL and its metal (II) complexes, 1–3 screened for their in vitro antimicrobial activities using the disc diffusion method against selected microbes. Complex 1 shows higher antimicrobial activity than complexes 2, 3 and Schiff base ligand HL. According to the results obtained from the cytotoxic studies, Schiff base ligand HL and its metal (II) complexes 1–3 have better cytotoxicity against MCF‐7 cell lines with potency higher than the currently used chemotherapeutic agent cyclophosphamide.     

2‐Methoxy‐4‐methylsulfinylbenzyl: A Backbone Amide Safety‐Catch Protecting Group for the Synthesis and Purification of Difficult Peptide Sequences

The use of 2‐methoxy‐4‐methylsulfinylbenzyl (Mmsb) as a new backbone amide‐protecting group that acts as a safety‐catch structure is proposed. Mmsb, which is stable during the elongation of the sequence and trifluoroacetic acid‐mediated cleavage from the resin, improves the synthetic process as well as the properties of the quasi‐unprotected peptide. Mmsb offers the possibility of purifying and characterizing complex peptide sequences, and renders the target peptide after NH₄I/TFA treatment and subsequent ether precipitation to remove the cleaved Mmsb moiety. First, the “difficult peptide” sequence H‐(Ala)₁₀‐NH₂ was selected as a model to optimize the new protecting group strategy. Second, the complex, bioactive Ac‐(RADA)₄‐NH₂ sequence was chosen to validate this methodology. The improvements in solid‐phase peptide synthesis combined with the enhanced solubility of the quasi‐unprotected peptides, as compared with standard sequences, made it possible to obtain purified Ac‐(RADA)₄‐NH₂. To extend the scope of the approach, the challenging Aβ(1‐42) peptide was synthesized and purified in a similar manner. The proposed Mmsb strategy opens up the possibility of synthesizing other challenging small proteins.     

Azo dye with nitrogen donor sets of atoms and its metal complexes: Synthesis,characterization, DFT,biological, anticancer and Molecular docking studies

An azo derivative was synthesized by coupling diazotized 2,6‐diaminopyridine with p‐dimethyl amino benzaldehyde and this new ligand formed a series of metal complexes with Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) salts. These complexes were characterized on the basis of elemental analyses, molar conductance, infrared spectroscopy, UV–Vis, ¹H NMR, mass spectrometry, electronic spectra, magnetic susceptibility and ESR spectral studies, conductivity measurements, thermogravimetric analyses (TG‐DTG). The molecular and electronic structure of the azo ligand was optimized theoretically and the quantum chemical parameters were calculated. The ligand and its metal complexes were subjected to X‐ray powder diffraction study. The thermal stability of the ligand and its metal complexes was examined by thermogravimetry. The ligand and its complexes were tested for their in vitro antimicrobial activity, some of the complexes showed good antimicrobial activities against some selected bacterial and fungal strains. Anticancer activity of the ligand and its metal complexes are evaluated against human cancer (MCF‐7 cells viability). Molecular docking was used to predict the binding between azo ligand and the receptors of nucleoside diphosphate kinase of Staphylococcus aureus (3Q8U) and (3HB5) which is breast cancer mutant oxidoreductase. The docking study provided useful structural information for inhibition studies.