Interaction of Mixed-Ligand Monolayer-Protected Au₁₄₄ Clusters with Biomimetic Membranes as a Function of the Transmembrane Potential

Understanding the interaction of nanoparticles with cell membranes is a high-priority research area for possible biomedical applications. We describe our findings concerning the interaction of Au144 monolayer-protected clusters (MPCs) with biomimetic membranes and their permeabilizing effect as a function of the transmembrane potential. We synthesized Au144(SCH2CH2Ph)60 and modified the capping monolayer with 8-mercaptooctanoic acid (Au144OctA) or thiolated trichogin (Au144TCG), a channel-forming peptide. The interactions of these MPCs with mercury-supported lipid mono- and bilayers were studied with a combination of electrochemical techniques specifically sensitive to changes in the properties of biomimetic membranes and/or charge-transfer phenomena. Permeabilization effects were evaluated through the influence of MPC uptake on the reduction of cadmium­(II) ions. The nature and properties of the Au144 capping molecules play a crucial role in controlling how MPCs interact with membranes. The native MPC causes a small effect, whereas both Au144OctA and Au144TCG interact significantly with the lipid monolayer and show electroactivity. Whereas Au144OctA penetrates the membrane, Au144TCG pierces the membrane with its peptide appendage while remaining outside of it. Both clusters promote Cd2+ reduction but with apparently different mechanisms. Because of the different way that they interact with the membrane, Au144OctA is more effective in Cd2+ reduction when interacting with the lipid bilayer and Au144TCG performs particularly well when piercing the lipid monolayer

Tuning the Reducing Properties of 1,2-Diaryl-1,2-disodiumethanes

We investigated the reducing properties of a series of 1,2-diaryl-1,2-disodiumethanes by means of equilibration reactions. The electron-donor power of these vic-diorganometals is strongly affected by the nature of substituents present either on the aromatic ring(s) or on the carbanionic centers, and it can be correlated with their ability to delocalize the arylmethyl carbanions. These findings are supported by electrochemical analysis of the reduction behavior of the parent 1,2-diarylalkene. Applications of these results to the reduction of selected substrates are described

Molecular Electron-Transfer Properties of Au₃₈ Clusters

The electron transfer (ET) properties of Au38 clusters protected by a phenylethanethiolate monolayer, Au38(SR)24, were studied in N,N-dimethylformamide and dichloromethane. The kinetic parameters of the first oxidation steps (+1/0 and +2/+1) and the first reduction step (0/−1) were obtained by electrochemical methods. The anion electrogenerated from Au38(SR)24 was employed in homogeneous redox catalysis experiments, using diphenyl disulfide and benzyl bromide as the acceptors. Both the heterogeneous and the homogeneous analyses pointed to the fast ET behavior typical for the formation and reactivity of delocalized ionic species with small intrinsic barriers. The results show that Au38 clusters are in all respects efficient redox molecules

Molecular Modeling Characterization of a Conformationally Constrained Monolayer-Protected Gold Cluster

We present a multilevel molecular modeling study aimed at elucidating physical and chemical properties of gold clusters capped by a monolayer of thiolated oligopeptides. The protecting peptides are based on the α-aminoisobutyric acid unit, form intramolecular CO···H−N bonds, and can form intermolecular hydrogen bonds. This study is motivated by recent breakthroughs into the determination of crystal structures of small gold clusters protected with small thiolated molecules. Such structures are characterized by surface gold atoms in the so-called “staple motifs”, as opposed to the commonly assumed structures in which thiolates bind to a high-symmetry gold cluster. It is unclear, however, whether the staple motif is common to all kinds of protecting layers, especially those made of polypeptides that are largely stabilized by intermolecular hydrogen bonding. Structural and spectroscopic properties are presented to understand the nature of peptide−peptide interactions, their structural arrangements, and their effect on the gold−thiol structural motif

Electroreduction of Dialkyl Peroxides. Activation−Driving Force Relationships and Bond Dissociation Free Energies^1a

The electrochemical reduction of five dialkyl peroxides in DMF was studied by cyclic voltammetry. The electron transfer (ET) to the selected compounds is concerted with the oxygen−oxygen bond cleavage (dissociative ET) and is independent of the electrode material. Such an electrochemical behavior provided the opportunity to study dissociative ETs by using the mercury electrode and therefore to test the dissociative ET theory by using heterogeneous activation−driving force relationships. The convolution voltammetry analysis coupled to the double-layer correction led to reasonable estimates of the standard potential (E°) for the dissociative ET to dialkyl peroxides, as supported, whenever possible, by independent estimates. A thermochemical cycle based on the dissociative ET concept was employed to calculate the bond dissociation free energies (BDFEs) of the five peroxides, using the above E°s together with electrochemical or thermochemical data pertaining to the redox properties of the leaving alkoxide ion. The BDFEs were found to be in the 25−32 kcal/mol range, suggesting a small substituent effect. The dissociative ET E°s were also used together with the experimental quadratic free energy relationships to estimate the heterogeneous reorganization energies

Theoretical and Electrochemical Analysis of Dissociative Electron Transfers Proceeding through Formation of Loose Radical Anion Species: Reduction of Symmetrical and Unsymmetrical Disulfides

The dissociative reduction of a series of symmetrical (RSSR, R = H, Me, t-Bu, Ph) and unsymmetrical disulfides (RSSR‘, R = H, R‘ = Me and R = Ph, R‘ = Me, t-Bu) was studied theoretically, by MO ab initio calculations and, for five of them, also experimentally, by convolution voltammetry in N,N-dimethylformamide. The reduction is dissociative but proceeds by a stepwise mechanism entailing the formation of the radical anion species. The electrochemical data led to estimated large intrinsic barriers, in agreement with an unusually large structural modification undergone by the disulfide molecules upon electron transfer. The theoretical results refer to MP2/3-21G*//MP2/3-21G*, MP2/3-21*G*//MP2/3-21G*, CBS-4M, and G2(MP2), the latter approach being used only for the molecules of small molecular complexity. A loose radical-anion intermediate was localized and the dissociation pattern for the relevant bonds analyzed. For all compounds, the best fragmentation pathway in solution is cleavage of the S−S bond. In addition, S−S bond elongation is the major structural modification undergone by the disulfide molecule on its way to the radical anion and eventually to the fragmentation products. The calculated energy of activation for the initial electron transfer was estimated from the crossing of the energy profiles of the neutral molecule and its radical anion (in the form of Morse-like potentials) as a function of the S−S bond length coordinate. The inner intrinsic barrier obtained in this way is in good agreement with that determined by convolution voltammetry, once the solvent effect is taken into account

Evidence Against the Hopping Mechanism as an Important Electron Transfer Pathway for Conformationally Constrained Oligopeptides

The rate constant of intramolecular electron transfer through oligopeptides based on the α-aminoisobutyric acid residue was determined as a function of the peptide length and found to depend weakly on the donor−acceptor separation. By measuring the electron-transfer activation energy and estimating the energy gap between donor and bridge, we were able to discard the electron hopping mechanism

Electrocrystallization of Monolayer-Protected Gold Clusters: Opening the Door to Quality, Quantity, and New Structures

Thiolate-protected metal clusters are materials of ever-growing importance in fundamental and applied research. Knowledge of their single-crystal X-ray structures has been instrumental to enable advanced molecular understanding of their intriguing properties. So far, however, a general, reliable, chemically clean approach to prepare single crystals suitable for accurate crystallographic analysis was missing. Here we show that single crystals of thiolate-protected clusters can be grown in large quantity and very high quality by electrocrystallization. This method relies on the fact that charged clusters display a higher solubility in polar solvents than their neutral counterparts. Nucleation of the electrogenerated insoluble clusters directly onto the electrode surface eventually leads to the formation of a dense forest of millimeter-long single crystals. Electrocrystallization of three known Au25(SR)180 clusters is described. A new cluster, Au25(S-nC5H11)18, was also prepared and found to crystallize by forming bundles of millimeter-long Au25 polymers

Formation and Cleavage of Aromatic Disulfide Radical Anions

The electron transfer (ET) to a series of para-substituted diaryl disulfides, having the general formula (X−C6H4S−)2, has been studied. The X groups were selected as to have a comprehensive variation of the substituent effect, being X = NH2, MeO, H, F, Cl, CO2Et, CN, and NO2. The reduction was carried out experimentally, using N,N-dimethylformamide as the solvent, and by molecular orbital (MO) ab initio calculations. The ET was studied heterogeneously, by voltammetric reduction and convolution analysis, and homogeneously, by using electrogenerated radical anions as the solution electron donors. The reduction is dissociative, leading to the cleavage of the S−S bond in a stepwise manner. Both experimental approaches led us to estimate the E° and the intrinsic barrier values for the formation of the radical anions. Comparison of the independently obtained results allowed obtaining, for the first time, a quantitative description of the correlation between heterogeneous and homogeneous rate constants of ETs associated with significant inner reorganization energy. The experimental outcome was fully supported by the theoretical calculations, which provided information about the disulfide lowest unoccupied MOs (LUMOs) and singly occupied MO (SOMO), the bond dissociation energies, and the most significant structural modifications associated with radical anion formation. With disulfides bearing electron-donating or mildly electron-withdrawing groups, the inner reorganization is particularly large, which reflects the significant stretching of the S−S bond experienced by the molecule upon ET. The process entails formation of loose radical anion species in which the SOMO is heavily localized, as the LUMO, onto the frangible bond. As a consequence of the formation of these σ*-radical anions, the S−S bond energy of the latter is rather small and the cleavage rate constant is very large. With electron-withdrawing groups, the extent of delocalization of the SOMO onto the aryl system increases, leading to a decrease of the reorganization energy for radical anion formation. Interestingly, while the LUMO now has π* character, the actual reduction intermediate (and thus the SOMO) is still a σ*-type radical anion. With the nitro-substituted disulfide, very limited inner reorganization is required and a π*-radical anion initially forms. A nondissociative type intramolecular ET then ensues, leading to the formation of a new radical anion whose antibonding orbital has similar features as those of the SOMO of the other diaryl disulfides. Therefore, independently of the substituent, the actual S−S bond cleavage occurs in a quite similar way along the series investigated. The S−S bond cleavage rate, however, tends to decrease as the Hammett σ increases, which would be in keeping with an increase of both the electronic and solvent reorganization energies

Influence of Surface Structure on Single or Mixed Component Self-Assembled Monolayers via in Situ Spectroelectrochemical Fluorescence Imaging of the Complete Stereographic Triangle on a Single Crystal Au Bead Electrode

The use of a single crystal gold bead electrode is demonstrated for characterization of self-assembled monolayers (SAM)­s formed on the bead surface expressing a complete set of face centered cubic (fcc) surface structures represented by a stereographic projection. Simultaneous analysis of many crystallographic orientations was accomplished through the use of an in situ fluorescence microscopic imaging technique coupled with electrochemical measurements. SAMs were prepared from different classes of molecules, which were modified with a fluorescent tag enabling characterization of the influence of electrical potential and a direct comparison of the influence of surface structure on SAMs adsorbed onto low index, vicinal and chiral surfaces. The assembly of alkylthiol, Aib peptide and DNA SAMs are studied as a function of the electrical potential of the interface revealing how the organization of these SAMs depend on the surface crystallographic orientation, all in one measurement. This approach allows for a simultaneous determination of SAMs assembled onto an electrode surface onto which the whole fcc stereographic triangle can be mapped, revealing the influence of intermolecular interactions as well as the atomic arrangement of the substrate. Moreover, this method enables study of the influence of the Au surface atom arrangement on SAMs that were created and analyzed, both under identical conditions, something that can be challenging for the typical studies of this kind using individual gold single crystal electrodes. Also demonstrated is the analysis of a SAM containing two components prepared using thiol exchange. The two component SAM shows remarkable differences in the surface coverage, which strongly depends on the surface crystallography enabling estimates of the thiol exchange energetics. In addition, these electrode surfaces enable studies of molecular adsorption onto the symmetry related chiral surfaces since more than one stereographic triangle can be imaged at the same time. The ability to observe a SAM modified surface that contains many complete fcc stereographic triangles will facilitate the study of the single and multicomponent SAMs, identifying interesting surfaces for further analysis