Electrochemical parameters and techniques in drug development, with an emphasis on quinones and related compounds

This review article summarizes recent applications of electrochemical techniques to redox-active drug development and mechanistic studies. It includes a general introduction to the use of electrochemistry in biology, with a focus on how electrochemistry can uniquely provide both kinetic and thermodynamic information. A number of studies are reported from the literature and the authors' laboratories, including the investigation of reactive oxygen species, biooxidative/bioreductive activation of pro-drugs, and DNA alkylation, with a particular emphasis on quinones and related compounds. Data from techniques ranging from traditional cyclic voltammetry to sophisticated single cell studies are presented. The examples herein presented illustrate how electrochemical, biochemical and medical knowledge can be integrated to develop strategies for the design and development of redox-selective therapeutics.     

Abel maps of Gorenstein curves

Abstract  For a Gorenstein curve X and a nonsingular point P∈ X, we construct Abel maps and , where J_Xⁱ is the moduli scheme for simple, torsion-free, rank-1 sheaves on X of degree i. The image curves of A and A_P are shown to have the same arithmetic genus of X. Also, A and A_P are shown to be embeddings away from rational subcurves L⊂ X meeting in separating nodes. Finally we establish a connection with Seshadri’s moduli scheme U_X(1) for semistable, torsion-free, rank-1 sheaves on X, obtaining an embedding of A(X) into U_X(1). Keywords Abel map, Torsion-free rank-1 sheaf, Compactified Jacobian, Gorenstein singularity Mathematics Subject Classification (2000) 14H40, 14H60     

A property of the β-Cauchy-type integral with continuous density

  A theorem from the classical complex analysis proved by Davydov in 1949 is extended to the theory of solution of a special case of the Beltrami equation in the z-complex plane (i.e., null solutions of the differential operator ). It is proved that if γ is a rectifiable Jordan closed curve and f is a continuous complex-valued function on γ such that the integral

Hearing the weights of weighted projective planes

Which properties of an orbifold can we “hear,” i.e., which topological and geometric properties of an orbifold are determined by its Laplace spectrum? We consider this question for a class of four-dimensional Kähler orbifolds: weighted projective planes \(M := {\mathbb{C}}P^2(N_1, N_2, N_3)\) with three isolated singularities. We show that the spectra of the Laplacian acting on 0- and 1-forms on M determine the weights N ₁, N ₂, and N ₃. The proof involves analysis of the heat invariants using several techniques, including localization in equivariant cohomology. We show that we can replace knowledge of the spectrum on 1-forms by knowledge of the Euler characteristic and obtain the same result. Finally, after determining the values of N ₁, N ₂, and N ₃, we can hear whether M is endowed with an extremal Kähler metric.     

On conjectures of Frankl and El‐Zahar

An induced subgraph of a graph is called a derived subgraph of if contains no isolated vertices. An edge e of is said to be residual if e occurs in more than half of the derived subgraphs of . In this article, we prove that every simple graph with at least one edge contains a non‐residual edge. This was conjectured by El‐Zahar in 1997. © 2008 Wiley Periodicals, Inc. J Graph Theory 57: 344–352, 2008     

Existence of Solutions for Second Order Partial Neutral Functional Differential Equations

We establish existence of mild solutions for a class of abstract second-order partial neutral functional differential equations with unbounded delay in a Banach space. The work of the second author was supported by FONDECYT-CONICYT, Grants 1050314 and 7050034.     

Inner reorganization during the radical-biradical transition in a nor-beta-lapachone derivative possessing two redox centers

In this work, the electrochemical behaviour of an antitumoral nitro o-quinone derivative obtained from 3-bromo-nor-beta-lapachone was studied. Cyclic voltammetric experiments, in acetonitrile solution, revealed that both quinone and nitro functions are reduced independently as quasi-reversible one-electron transfer processes in this order. Depending on the reduction potential, a radical anion or a biradical dianion is obtained. The formation of these paramagnetic species was confirmed by performing in situ Electrochemical-Electron Spin Resonance (E-ESR) experiments. Analysis of the kinetics of electron transfer associated to those electron uptake processes, in terms of the Marcus-Hush-Levich model, revealed differences in the reorganization energy (lambda((k))) for both steps (lambda((I)): 1.07-1.11 eV; lambda((II)): 1.21-1.30 eV). By evaluating the conformations of the radical and biradical systems by calculations at the BLYP//TZVP level of theory, it was found that the inner component, for the second reduction process (lambda((II))) was approximately 72% of lambda((II)), reflecting modifications in the molecular structure during the radical anion-biradical dianion transition. This change is also reflected in the differences presented by line widths of the ESR signals of both electrogenerated radical and diradical species.     

Tuning the Catalytic Activity of a Pincer Complex of Rhodium(I) by Supramolecular and Redox Stimuli

We report the rhodium(I) complex [Rh(CNC−NDI)(CO)]⁺, in which CNC−NDI refers to a pincer-CNC ligand decorated with a naphthalenediimide moiety. Due to the presence of the planar CNC ligand and the naphthalenediimide moiety, the electronic nature of the complex can be modulated by means of supramolecular and redox stimuli, respectively. The metal complex shows a strong π–π-stacking interaction with coronene. This interaction has an impact on the electron-richness of the metal, as demonstrated by the shifting of the ν(CO) stretching band to a lower frequency. The addition of tetrabutylammonium fluoride facilitates the sequential one- and two-electron reduction of the NDI moiety of the ligand, thus resulting in a situation in which the ligand can increase its electron-donor strength in two levels. The nature of the interaction with the fluoride anion was studied computationally. The catalytic activity of the [Rh(CNC−NDI)(CO)]⁺ complex was tested in the cycloisomerization of alkynoic acids, where it is observed that the activity of the catalyst can be modulated between four levels of activity, which correspond to i) the use of the unmodified catalyst, ii) catalyst+coronene, iii) catalyst+2 equivalents of fluoride, and iv) catalyst+5 equivalents of fluoride.     

Supramolecular Control of the Oxidative Addition as a Way To Improve the Catalytic Efficiency of Pincer-Rhodium (I) Complexes

¹H NMR studies using a cationic complex with a pyridine-di-imidazolylidene pincer ligand of formula [Rh(CNC)(CO)]⁺ revealed that this compound showed high binding affinity with coronene in CH₂Cl₂. The interaction between coronene and the planar Rh^I complex is established by means of π-stacking interactions. This interaction has a strong impact on the electron-donating strength of the pincer CNC ligand, which is increased significantly, as demonstrated by the shifting of the ν(CO) stretching bands to lower frequencies. The addition of coronene increases the reaction rate of the nucleophilic attack of methyl iodide on the rhodium (I) pincer complex, and also has a positive effect on the performance of the complex as a catalyst in the cycloisomerization of 4-pentynoic acid. These findings highlight the importance of supramolecular interactions for tuning the reactivity and catalytic activity of square-planar metal complexes.     

Supramolecular adsorption of alkaloids by metallosalphen complexes

Mono and bis-zinc(II)-centered salphen derivatives 1-5 are presented as efficient adsorption materials for pyridine-based alkaloid derivatives. The different alkaloid assemblies were studied by UV-vis and NMR spectroscopy, and high binding constants (Ks approximately 10(5)) were additionally determined for the supramolecular complexes based on nicotine. X-ray analyses furthermore revealed, together with spectroscopic solution data, a preferential positioning of the nicotine guest(s). Upon binding to bis-Zn(II)-bis-salphen complexes, the dinicotine assembly provokes a colorimetric change that may be useful for colorimetric analyses. The adsorption/desorption process of nicotine was studied using a polymeric bis-Zn(salphen) complex (5) and showed a recycling potential of this type of complexes in the binding of alkaloid compounds.