Diane K. Smith

Electrochemically controlled hydrogen bonding. o-Quinones as simple redox-dependent receptors for arylureas.

9,10-Phenanthrenequinone and acenaphthenequinone are shown to act as simple redox-dependent receptors toward aromatic ureas in CH(2)Cl(2) and DMF. Reduction of the o-quinones to their radical anions greatly increases the strength of hydrogen bonding between the quinone carbonyl oxygens and the urea N-hydrogens. This is detected by large positive shifts in the redox potential of the quinones with no change in electrochemical reversibility upon addition of urea guests. Cyclic voltammetric studies with a variety of possible guests show that the effect is quite selective. Only guests with two strong hydrogen donors, such as O-H bonds or amide N-H bonds, that are capable of simultaneously interacting with both carbonyl oxygens give large shifts in the redox potential of the quinones. The electronic character and conformational preference of the guest are also shown to significantly affect the magnitude of the observed potential shift. In the presence of strong proton donors the electrochemistry of the quinone becomes irreversible indicating that proton transfer has taken place. Experiments with compounds of different acidity show that the pK(a) of the protonated quinone radical is about 15 on the DMSO scale, >4 pK(a) units smaller than that of 1,3-diphenylurea. This is further proof that hydrogen bonding and not proton transfer is responsible for the large potential shifts observed with this and similar guests.

Synthesis and electrochemistry of 2-ethenyl and 2-ethanyl derivatives of 5-nitroimidazole and antimicrobial activity against Giardia lamblia.

Infections with the diarrheagenic pathogen, Giardia lamblia, are commonly treated with the 5-nitroimidazole (5-NI) metronidazole (Mz), and yet treatment failures and Mz resistance occur. Using a panel of new 2-ethenyl and 2-ethanyl 5-NI derivatives, we found that compounds with a saturated bridge between the 5-NI core and a pendant ring system exhibited only modestly increased antigiardial activity and could not overcome Mz resistance. By contrast, olefins with a conjugated bridge connecting the core and a substituted phenyl or heterocyclic ring showed greatly increased antigiardial activity without toxicity, and several overcame Mz resistance and were more effective than Mz in a murine giardiasis model. Determination of the half-wave potential of the initial one-electron transfer by cyclic voltammetry revealed that easier redox activation correlated with greater antigiardial activity and capacity to overcome Mz resistance. These studies show the potential of combining systematic synthetic approaches with biological and electrochemical evaluations in developing improved 5-NI drugs.

Electrochemically Controlled Hydrogen Bonding. Electrolyte Effects in an Oxidation-Based Arylurea−Amide System

Oxidation of a dimethylaminophenyl-substituted urea leads to a > 2000-fold increase in binding strength between the urea and a diamide guest in 0.1 M NBu4B(C6F5)4/CH2Cl2. The strength of this interaction is obscured when NBu4ClO4 or NBu4PF6 is used as the electrolyte due to competition between the neutral guest and the electrolyte anion for H-bonding to the urea cation.

N,N′-dimethyl-2,7-diazapyrenium: a redox-dependent receptor for aromatic carboxylates

Abstract Studies are presented showing that N,N′-dimethyl-2,7-diazapyrenium, DAP 2+ , acts as a redox-dependent receptor for aromatic carboxylates in aqueous solution. Cyclic voltammetric studies of DAP 2+ by itself indicate that its one-electron reduction to DAP + is only quasi-reversible in both aqueous and acetonitrile solutions due to the slow oxidation of DAP + back to DAP 2+ . In aqueous solution, the oxidation is very sensitive to other conditions such as pH and the presence of small amounts of iodide. However, in pH 7 phosphate buffer, fairly reversible voltammetry is observed at slow scan rates. Under these conditions, addition of excess aromatic carboxylate results in large negative shifts in the E 1/2 of DAP 2+/+ . Similar changes are observed in the 1 H NMR spectrum of DAP 2+ in the presence of the different carboxylates, indicating that the potential shift is due to strong interactions between the carboxylates and DAP 2+ . Upon reduction, the favorable coulombic interactions between the anionic carboxylates and the cationic pyrenium are weakened, resulting in the observed negative shifts in E 1/2 . Although the perturbation of electrostatic interactions causes the potential shifts, the magnitude of the shifts correlates more with the strength of π-stacking interactions between the carboxylates and DAP 2+ . Those carboxylates whose π system can come into maximum close contact with the DAP 2+ π system give the largest potential shifts.

Ruthenium Complexes of 2,2′‐Bipyridine‐6,6′‐diphosphonate Ligands for Water Oxidation

Two novel ruthenium complexes, [Ru(2,2′‐bipyridine‐6,6′‐diphosphonato)(pic)2] (2) (pic=4‐picoline) and [Ru(6,6′‐diisopropyl‐2,2′‐bipyridine‐6,6′‐diphosphonato)(pic)2] (3) bearing phosphonate groups have been synthesized and characterized by NMR spectroscopy, elemental analyses, X‐ray crystallography, cyclic voltammetry, and UV/Vis spectroscopy. Both complexes show catalytic water oxidation activity by electrochemistry. At pH 7, the RuII/III redox couple of 2 is observed at a lower potential than that of 3, yet significantly, 3 oxidizes water at a lower onset potential. At pH 1 however, 2 and 3 have comparable catalytic reactivity using sacrificial oxidant CeIV. We propose that water oxidation activities of 2 and 3 are influenced by overall charges. For example, in oxidizing from RuII to RuIII at pH 7, 2 acquires a −1 overall charge whereas 3 acquires a +1 charge. Charge‐dictated electrostatic effects may govern binding of a water molecule to the metal site.

Redox-Responsive Dimerization in a Ferrocene-Ureidopyrimidone Supramolecular Assembly

Ureidopyrimidones (UPys) are well-known to dimerize via 4 strong H-bonds in noncompetitive solvents. Although UPy dimers have been widely studied, there are few examples of UPys containing redox-active groups, and even fewer in which oxidation/reduction has been shown to affect dimerization. In this study, a thorough electrochemical investigation of a UPy with a ferrocene attached to the 6-position of the pyrimidone ring, UPy(Fc), demonstrates that strong and reversible redox-control of dimerization is possible in the UPy system. 1H NMR shows that the reduced UPy(Fc) is fully dimerized under electrochemical conditions in CH2Cl2. Cyclic voltammetry (CV) shows that oxidation of the ferrocene to the ferrocenium converts the dimer to another species with a less positive E1/2, and that reduction of this species reforms the dimer in a chemically reversible fashion. Analysis of the scan rate and concentration dependence of the CVs along with the relative diffusion coefficient measurements strongly suggest that the oxidized form is the monomer. Simulation of the CV data gives a Kdis of 2.1 × 10-6 M in the reduced state and 12 M in the oxidized state. This large redox dependence is likely due to oxidation creating both electrostatic repulsion between monomers and greatly decreasing the H-accepting ability of the pyrimidone.