pH dependent binding in de novo hetero bimetallic coiled coils

Herein the first example of a bimetallic coiled coil featuring a lanthanide binding site is reported, opening opportunities to exploit the attractive NMR and photophysical properties of the lanthanides in multi metallo protein design. In our efforts to fully characterise the system we identified for the first time that lanthanide binding to such sites is pH dependent, with optimal binding at neutral pH, and that the double AsnAsp site is more versatile in this regard than the single Asp site. Our second site featured the structural HgCys3 site, the chemistry of which was essentially unaltered by the presence of the lanthanide site. In fact, both metal binding sites within the hetero bimetallic coiled coil displayed the same properties as their mononuclear single binding site controls, and operated independently of each other. Finally, pH can be used as an external trigger to control the binding of Hg(II) and Tb(III) to the two distinct sites within this coiled coil, and offers the opportunity to “activate” metal binding sites within complex multi metallo and multi-functional designs

A single-pot template reaction towards a manganese-based T1 contrast agent

Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL Me, and studied the most important physicochemical properties in vitro. MnL Me displays optimized r 1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r 1 b=21.1 mM −1 s −1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (K a=4.2×10 3 M −1). In vivo studies show that MnL Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL Me shows great promise as a novel MRI contrast agent

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents

We report the preparation and spectroscopic characterization of a highly elusive copper site bound exclusively to oxygen donor atoms within a protein scaffold. Despite copper generally being considered unsuitable for use in MRI contrast agents, which in the clinic are largely Gd(III) based, the designed copper coiled coil displays relaxivity values equal to, or superior than, those of the Gd(III) analog at clinical field strengths. The creation of this new-to-biology proteinaceous CuOx-binding site demonstrates the power of the de novo peptide design approach to access chemistry for abiological applications, such as for the development of MRI contrast agents

Electrochemical, phosphate hydrolysis, DNA binding and DNA cleavage properties of new polyaza macrobicyclic dinickel(II) complexes

A new class of macrobicyclic dinickel(II) complexes Ni2L1,2 B](ClO4)(4) (1-6), where L-1,L-2 are polyaza macrobicyclic binucleating ligands, and B is a N,N-donor heterocyclic base (viz. 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)) are synthesized and characterized. The redox, catalytic, DNA binding and DNA cleavage properties were studied. They exhibit two irreversible waves in the cathodic region around E-pc = -0.95 V and E-pa = -0.85 V vs. Ag/Ag+ in CH3CN-0.1 M TBAP, respectively. The first order rate constants for the hydrolysis of 4-nitrophenylphosphate to 4-nitrophenolate by the dinickel(II) complexes 1-6 are in the range from 3.36 x 10(-5) to 10.83 x 10(-5) Ms-1. The complexes 3 and 6 show good binding propensity to calf thymus DNA giving binding constant values (K-b) in the range from 3.08 x 10(5) to 5.37 x 10(5) M-1. The binding site sizes and viscosity data suggest the DNA intercalative and/or groove binding nature of the complexes. The complexes display significant hydrolytic cleavage of supercoiled pBR322DNA at pH 7.2 and 37 degrees C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo Michaelis-Menten kinetic parameters k(cat) = 5.44 x 10(-2) h(-1) and K-M = 6.23 x 10(-3) M for complex 3 were obtained. Complex 3 also shows an enormous enhancement of the cleavage rate, of 1.5 x 10(6), in comparison to the uncatalysed hydrolysis rate (k = 3.6 x 10(-8) h(-1)) of ds-DNA

Structural, electrochemical, phosphate-hydrolysis, DNA binding and cleavage studies of new macrocyclic binuclear nickel(II) complexes

New macrocyclic binuclear nickel(II) complexes have been synthesized by using the bicompartmental mononuclear complex [NiL] [3,30-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various diamines like 1,2-bis(aminooxy)ethane (L1), 1,2-diamino ethane (L2), 1,3-diamino propane (L3), 1,4-diamino butane (L4), 1,2-diamino benzene (L5), and 1,8-diamino naphthalene (L6). The complexes were characterized by elemental analysis and spectroscopic methods. The molecular structures of the symmetrical binuclear complex [Ni2L1(H2O)4](ClO4)2 (1) and unsymmetrical binuclear complex [Ni2L3(H2O)4](ClO4)2·(H2O)4 (3) were determined by single-crystal X-ray diffraction. The geometry around both the nickel(II) ions in each molecule is a slightly distorted octahedral. The distance between the Ni⋯Ni centers for complex 1 is 3.039 Å and for complex 3 is 3.059 Å. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, phosphate hydrolysis, DNA binding and cleavage properties have been studied. Electrochemical studies of the complexes show two quasi-reversible one electron reduction processes between −0.49 to −1.69 V. The reduction potential of the binuclear Ni(II) complexes shifts towards anodically upon increasing the macrocyclic ring size. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate reaction are in the range from 8.69 × 10−3 to 1.85 × 10−2 s−1. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 1.4 × 104 to 17.5 × 104 M−1. The absorption, fluorescence and CD spectral data suggests that the complexes are strongly interacting with DNA. These complexes display hydrolytic cleavage of supercoiled pBR322DNA in the presence of H2O2 at pH 7.2 and 37 °C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo-Michaelis–Menten kinetic parameters kcat = 1.27 ± 0.4 h−1 and KM = 7.7 × 10−2 M for naphthalene diimine containing macrocyclic binuclear nickel(II) complex, (6) were obtained

Catalytic activity of a benzoyl hydrazone based dimeric dicopper(II) complex in catechol and alcohol oxidation reactions

The benzoyl hydrazone based dimeric dicopper(II) complex [Cu2(R)(CH3O)(NO3)]2(CH3O)2 (R-Cu2+), recently reported by us, catalyzes the aerobic oxidation of catechols (catechol (S1), 3,5- itertiarybutylcatechol (S2) and 3-nitrocatechol (S3)) to the corresponding quinones (catecholase like activity), as shown by UV–Vis absorption spectroscopy in methanol/HEPES buffer (pH 8.2) medium at 25 C. The highest activity is observed for the substituted catechol (S2) with the electron donor tertiary butyl group, resulting in a turnover frequency (TOF) value of 1.13 103 h1. The complex R-Cu2+ also exhibits a good catalytic activity in the oxidation (without added solvent) of 1-phenylethanol to acetophenone by But OOH under low power (10 W) microwave (MW) irradiation. 2014 Elsevier B.V. All rights reserved

Electrochemical properties of Robson type macrocyclic dicopper(II) complexes

The redox properties of the 1,10-phenanthroline containing Robson type symmetrical macrocyclic dicopper(II) complex [Cu2L(H2O.phen)2](ClO4)2 1 (L = μ-11,23-dimethyl-3,7,15,19-tetraazatricyclo-[19.3.1.18 19,13,21] he p t a c o s a-1(24) , 2, 7, 9, 11, 13(26), 14, 19, 21(25), 22-decaene-25,26-diolate) and of its dicopper(II) precursor [Cu2L(H2O)2](ClO4)2 2 have been investigated by cyclic voltammetry and controlled potential electrolysis in different organic solvents. They exhibit two consecutive reversible one-electron reductions assigned to the CuIICuII ® CuICuII ® CuICuI cathodic processes. The results suggest that, in solution, phenanthroline does not coordinate to the metal in complex 1, but its H-bonding interaction with the water ligands can be preserved.info:eu-repo/semantics/publishedVersio

Naphthalimide-phenanthroimidazole incorporated new fluorescent sensor for “turn-on” Cu2+ detection in living cancer cells

In recent years, fluorescent sensors have emerged as attractive imaging probes due to their distinct responses toward bio-relevant metal ions. However, the bioimaging application main barrier is the ‘turn-off’ response toward paramagnetic metal ions such as Cu2+ under physiological conditions. Herein, we report a new sensor (2-methyl(4-bromo-N-ethylpiperazinyl-1,8-naphthalimido)-4-(1H-phenanthro[9,10-d]imidazole-2-yl) phenol) NPP with multifunctional (Naphthalimide, Piperazine, Phenanthroimidazole) units for fluorescent and colourimetric detection of Cu2+ in an aqueous medium. Both absorption and fluorescence spectral titration strategies were used to monitor the Cu2+-sensing property of NPP. The NPP displays a weak emission at ca. 455 nm, which remarkably enhances (⁓3.2-fold) upon selective binding of Cu2+ over a range of metal ions, including other paramagnetic metal ions (Mn2+, Fe3+, Co2+). The stoichiometry, binding constant (Ka) and the LOD (limit of detection) of NPP toward Cu2+ ions were found to be 1:1, 5.0 (± 0.2) × 104 M−1 and 6.5 (± 0.4) × 10−7 M, respectively. We have also used NPP as a fluorescent probe to detect Cu2+ in live (human cervical HeLa) cancer cells. The emission intensity of NPP was almost recovered in HeLa cells by incubating ‘in situ’ the derived Cu2+ complex (NPP-Cu 2+ ) in the presence of a benchmark chelating agent such as EDTA (ethylenediaminetetraacetate). The fluorescent emission of NPP was reverted significantly in each cycle upon sequencial addition of Cu2+ and EDTA to the NPP solution. Overall, NPP is a novel, simple, economic and portable sensor that can detect Cu2+ in biological and environmental scenarios

Naphthalene Carbohydrazone Based Dizinc(II) Chemosensor for a Pyrophosphate Ion and Its DNA Assessment Application in Polymerase Chain Reaction Products

A new naphthalene carbohydrazone based dizinc(II) complex has been synthesized and investigated to act as a highly selective fluorescence and visual sensor for a pyrophosphate ion with a quite low detection limit of 155 ppb; this has also been used to detect the pyrophosphate ion released from polymerase-chain-reaction