Redox-active self-assembled monolayers (SAMs) provide an excellent platform for investigating electron transfer kinetics. Using a well-defined bridge, a redox center can be positioned at a fixed ...distance from the electrode and electron transfer kinetics probed using a variety of electrochemical techniques. Cyclic voltammetry, AC voltammetry, electrochemical impedance spectroscopy, and chronoamperometry are most commonly used to determine the rate of electron transfer of redox-activated SAMs. A variety of redox species have been attached to SAMs, and include transition metal complexes (e.g., ferrocene, ruthenium pentaammine, osmium bisbipyridine, metal clusters) and organic molecules (e.g., galvinol, C
60). SAMs offer an ideal environment to study the outer-sphere interactions of redox species. The composition and integrity of the monolayer and the electrode material influence the electron transfer kinetics and can be investigated using electrochemical methods. Theoretical models have been developed for investigating SAM structure. This review discusses methods and monolayer compositions for electrochemical measurements of redox-active SAMs.
The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the ...urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na
-dependent Cl
/HCO
exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl
/HCO
exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.
We have developed a modular architecture for preparing high-relaxivity multiplexed probes utilizing click chemistry. Our system incorporates azide bearing Gd(III) chelates and a trialkyne scaffold ...with a functional group for subsequent modification. In optimizing the relaxivity of this new complex, we undertook a study of the linker length between a chelate and the scaffold to determine its effect on relaxivity. The results show a strong dependence on flexibility between the individual chelates and the scaffold with decreasing linker length leading to significant increases in relaxivity. Nuclear magnetic resonance dispersion (NMRD) spectra were obtained to confirm a 10-fold increase in the rotational correlation time from 0.049 to 0.60 ns at 310 K. We have additionally obtained a crystal structure demonstrating that modification with an azide does not impact the coordination of the lanthanide. The resulting multinuclear center has a 500% increase in per Gd (or ionic) relaxivity at 1.41 T versus small molecule contrast agents and a 170% increase in relaxivity at 9.4 T.
The efficiency of Gd(III) contrast agents in magnetic resonance image enhancement is governed by a set of tunable structural parameters. Understanding and measuring these parameters requires specific ...analytical techniques. This Feature describes strategies to optimize each of the critical Gd(III) relaxation parameters for molecular imaging applications and the methods employed for their evaluation.
The kinetic and thermodynamic ligand exchange dynamics are important considerations in the rational design of metal-based therapeutics and therefore, require detailed investigation. Co(III) Schiff ...base complex derivatives of bis(acetylacetone)ethylenediimine acacen have been found to be potent enzyme and transcription factor inhibitors. These complexes undergo solution exchange of labile axial ligands. Upon dissociation, Co(III) irreversibly interacts with specific histidine residues of a protein, and consequently alters structure and causes inhibition. To guide the rational design of next generation agents, understanding the mechanism and dynamics of the ligand exchange process is essential. To investigate the lability, pH stability, and axial ligand exchange of these complexes in the absence of proteins, the pD- and temperature-dependent axial ligand substitution dynamics of a series of N-heterocyclic Co(acacen)(X)2+ complexes where X = 2-methylimidazole (2MeIm), 4-methylimidazole (4MeIm), ammine (NH3), N-methylimidazole (NMeIm), and pyridine (Py) were characterized by NMR spectroscopy. The pD stability was shown to be closely related to the nature of the axial ligand with the following trend toward aquation: 2MeIm > NH3 ≫ 4MeIm > Py > Im > NMeIm. Reaction of each Co(III)(acacen)(X)2+ derivative with 4MeIm showed formation of a mixed ligand Co(III) intermediate via a dissociative ligand exchange mechanism. The stability of the mixed ligand adduct was directly correlated to the pD-dependent stability of the starting Co(III) Schiff base with respect to Co(acacen)(4MeIm)2+. Crystal structure analysis of the Co(acacen)(X)2+ derivatives confirmed the trends in stability observed by NMR spectroscopy. Bond distances between the Co(III) and the axial nitrogen atoms were longest in the 2MeIm derivative as a result of distortion in the planar tetradentate ligand, and this was directly correlated to axial ligand lability and propensity toward exchange.
Dithiocarbamates (dtcs) have been implicated as important gold-binding groups in molecular electronics. Dtcs have two alkane branches connected at a single anchoring point that has a bidentate ...resonance structure. Forming readily in situ by the combination of secondary amines and CS2, dtcs adsorb quickly onto gold surfaces. Electroactive self-assembled monolayers (eSAMs) were prepared by the coadsorption of ferrocene dialkyldithiocarbamates (Fc dtcs) with diluent dtcs on gold electrodes. Short and long alkane chains were used (11 and 16 methylene groups, respectively), and a polar ester group was incorporated. Cyclic voltammetry (CV) shows that the electrochemistry is quasi-reversible. At high surface coverage, the peak separations and full widths at half-maximum for Fc dtcs deviate from theoretical values and are analogous to that of ferrocene alkane thiols on gold at high surface coverage. Importantly, these features do not change at low Fc dtc surface coverage as observed for ferrocene alkane thiols. Ferrocene dtcs were used to label monolayer defect sites and to demonstrate the exchange of surface-bound dtcs with solution dtcs. Finally, the rate of electron transfer was analyzed using Tafel plots and ac voltammetric methods. The results for both techniques are consistent with a kinetically disperse population of redox sites. The length of the diluent alkane chain appears to have an effect on the distribution of electron-transfer rates, likely because of the eSAM structure. This work indicates that structurally, Fc dtc eSAMs are fundamentally different from alkane thiol SAMs on gold.
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► Cobalt is a versatile transition metal for drug development. ► The tunable physicochemical properties can be exploited by understanding the mechanism of bioactive cobalt complexes. ...► The review highlights examples of mechanistic investigations of cobalt therapeutics.
Inorganic complexes are versatile platforms for the development of potent and selective pharmaceutical agents. Cobalt possesses a diverse array of properties that can be manipulated to yield promising drug candidates. Investigations into the mechanism of cobalt therapeutic agents can provide valuable insight into the physicochemical properties that can be harnessed for drug development. This review presents examples of bioactive cobalt complexes with special attention to their mechanisms of action. Specifically, cobalt complexes that elicit biological effects through protein inhibition, modification of drug activity, and bioreductive activation are discussed. Insights gained from these examples reveal features of cobalt that can be rationally tuned to produce therapeutics with high specificity and improved efficacy for the biomolecule or pathway of interest.
Ultrasmall (3, 4, 5, and 6 nm), water-soluble Fe3O4 magnetic nanoparticles were synthesized in diethylene glycol (DEG) via a facile one-pot reaction. Hydrodynamic size and relaxation time ...measurements did not show particle aggregation when Fe3O4 nanoparticles were dispersed in phosphate buffered saline, fetal bovine serum, or calf bovine serum for 1 week. Furthermore, the new Fe3O4 nanoparticles tolerated high salt concentrations (≤1 M NaCl) and a wide pH range from 5 to 11. Surface modification of the nanoparticles with poly(ethylene glycol) bis(carboxymethyl) ether (HOOC-PEG-COOH, 600 g/mol) was accomplished through a ligand-exchange reaction. The effects of PEG modification on magnetization and relaxivity of the Fe3O4 nanoparticles were investigated, and the results indicate that the increase in transverse relaxivity after PEG modification may be due to the increased volume of slowly diffusing water surrounding each nanoparticle. In vitro experiments showed that the DEG- and PEG-coated Fe3O4 nanoparticles have little effect on NIH/3T3 cell viability.
A one-pot reaction process was developed to synthesize highly dispersible, superparamagnetic Fe(3)O(4) nanoflowers; the potential of these nanoflowers as MRI contrast agents was investigated.
We report the synthesis and characterization of new ruthenium and rhenium nucleosides Ru(tolyl-acac)2(IMPy)-T (tolyl-acac = di(p-methylbenzonatemethane), IMPy = 2‘-iminomethylpyridine, T = thymidine) ...(5) and Re(CO)3(IMPy)-TCl (9), respectively. Structural analysis of 9 shows that the incorporation of this metal complex causes minimal perturbation to the sugar backbone and the nucleobase. Eletrochemical (5, E 1/2 = 0.265 V vs NHE; 9, E 1/2 = 1.67 V vs NHE), absorption (5, λmax = 600, 486 nm; 9, λmax = 388 nm), and emission (9, λmax = 770 nm, π = 17 ns) data indicate that 5 and 9 are suitable probes for DNA-mediated ground-state electron-transfer studies. The separation and characterization of diastereoisomers of 5 and bipyridyl-based ruthenium nucleoside Ru(bpy)2(IMPy)-T2+ (7) are reported.
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