Interactions of Functionalized PAMAM Dendrimers with Model Cell Membranes Studied via Spin-Labeling Technique

Polyamidoamine (PAMAM) dendrimers are exploited as drug carriers in various biomedical research fields, especially cancer therapy. The present study analyzes the interactions occurring between differently functionalized PAMAM dendrimers, namely, amine, acetamide, and 3-methoxy-carbonyl-5-pyrrolidonyl (“pyrrolidone”), and model membranes, namely, sodium dodecyl sulfate (SDS), sodium hexadecylsulfate (SHS) micelles, and egg-lecithin liposomes. For this purpose, the dendrimers were spin-labeled with the 3-carbamoyl-PROXYL radical. 1H-NMR spectra allowed the verification not only that labeling was successful but also that acetamide and (even more so) pyrrolidone functions shield the proton signals from the influence of the neighboring nitroxide groups. The computer-aided analysis of the electron paramagnetic resonance (EPR) spectra showed that the dendrimers with the acetamide function largely (60%) entered the SDS–micelles interface, while the amino-dendrimer electrostatically interacted with both the SDS and SHS surface forming dendrimer aggregates in solution. The pyrrolidone-dendrimers showed an intermediate behavior between those with the amino and acetamide functions. The acetamide- and pyrrolidone-dendrimers weakly interacted with the lecithin liposome surface, with a synergy between hydrophilic and hydrophobic interactions. Conversely, liposomes/amino-dendrimers interactions were quite strong and led to dendrimer aggregation at the liposome surface in solution. This information showed that acetamide- and pyrrolidone-dendrimers may be used as good alternatives to amino-dendrimers for drug delivery

Effect of Hydrogenated Cardanol on the Structure of Model Membranes Studied by EPR and NMR

Hydrogenated cardanol (HC) is known to act as an antiobesity, promising antioxidant, and eco-friendly brominating agent. In this respect, it is important to find the way to transport and protect HC into the body; a micellar structure works as the simplest membrane model and may be considered a suitable biocarrier for HC. Therefore, it is useful to analyze the impact of HC in the micellar structure and properties. This study reports a computer aided electron paramagnetic resonance (EPR) and ¹H NMR investigation of structural variations of cetyltrimetylammonium bromide (CTAB) micelles upon insertion of HC at different concentrations and pH variations. Surfactant spin probes inserted in the micelles allowed us to get information on the structure and dynamics of the micelles and the interactions between HC and CTAB. The formation of highly packed HC-CTAB mixed micelles were favored by the occurrence of both hydrophobic (chain–chain) and hydrophilic (between the polar and charged lipid heads) interactions. These interactions were enhanced by neutralization of the acidic HC heads. Different HC localizations into the micelles and micellar structures were identified by changing HC/CTAB relative concentrations and pH. The increase in HC concentration generated mixed micelles characterized by an increased surfactant packing. These results suggested a rod-like shape of the mixed micelles. The increase in pH promoted the insertion of deprotonated HC into less packed micelles, favored by the electrostatic head–head interactions between CTAB and deprotonated-HC surfactants

Effect of Hydrogenated Cardanol on the Structure of Model Membranes Studied by EPR and NMR

Hydrogenated cardanol (HC) is known to act as an antiobesity, promising antioxidant, and eco-friendly brominating agent. In this respect, it is important to find the way to transport and protect HC into the body; a micellar structure works as the simplest membrane model and may be considered a suitable biocarrier for HC. Therefore, it is useful to analyze the impact of HC in the micellar structure and properties. This study reports a computer aided electron paramagnetic resonance (EPR) and ¹H NMR investigation of structural variations of cetyltrimetylammonium bromide (CTAB) micelles upon insertion of HC at different concentrations and pH variations. Surfactant spin probes inserted in the micelles allowed us to get information on the structure and dynamics of the micelles and the interactions between HC and CTAB. The formation of highly packed HC-CTAB mixed micelles were favored by the occurrence of both hydrophobic (chain–chain) and hydrophilic (between the polar and charged lipid heads) interactions. These interactions were enhanced by neutralization of the acidic HC heads. Different HC localizations into the micelles and micellar structures were identified by changing HC/CTAB relative concentrations and pH. The increase in HC concentration generated mixed micelles characterized by an increased surfactant packing. These results suggested a rod-like shape of the mixed micelles. The increase in pH promoted the insertion of deprotonated HC into less packed micelles, favored by the electrostatic head–head interactions between CTAB and deprotonated-HC surfactants

EPR and Rheological Study of Hybrid Interfaces in Gold–Clay–Epoxy Nanocomposites

With the aim to obtain new materials with special properties to be used in various industrial and biomedical applications, ternary “gold–clay–epoxy” nanocomposites and their nanodispersions were prepared using clay decorated with gold nanoparticles (AuNPs), at different gold contents. Nanocomposites structure was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Rheology and electron paramagnetic resonance (EPR) techniques were used in order to evaluate the molecular dynamics in the nanodispersions, as well as dynamics at interfaces in the nanocomposites. The percolation threshold (i.e., the filler content related to the formation of long-range connectivity of particles in the dispersed media) of the gold nanoparticles was determined to be ϕ_p = 0.6 wt % at a fixed clay content of 3 wt %. The flow activation energy and the relaxation time spectrum illustrated the presence of interfacial interactions in the ternary nanodispersions around and above the percolation threshold of AuNPs; these interfacial interactions suppressed the global molecular dynamics. It was found that below ϕ_p the free epoxy polymer chains ratio dominated over the chains attracted on the gold surfaces; thus, the rheological behavior was not significantly changed by the presence of AuNPs. While, around and above ϕ_p, the amount of the bonded epoxy polymer chains on the gold surface was much higher than that of the free chains; thus, a substantial increase in the flow activation energy and shift in the spectra to higher relaxation times appeared. The EPR signals of the nanocomposites depended on the gold nanoparticle contents and the preparation procedure thus providing a fingerprint of the different nanostructures. The EPR results from spin probes indicated that the main effect of the gold nanoparticles above ϕ_p, was to form a more homogeneous, viscous and polar clay–epoxy mixture at the nanoparticle surface. The knowledge obtained from this study is applicable to understand the role of interfaces in ternary nanocomposites with different combinations of nanofiller

Copper(II) Complexes with 4‑Carbomethoxypyrrolidone Functionalized PAMAM-Dendrimers: An EPR Study

The internal flexibility and interacting ability of PAMAM-dendrimers having 4-carbomethoxypyrrolidone-groups as surface groups (termed Gn-Pyr), which may be useful for biomedical purposes, and ion traps were investigated by analyzing the EPR spectra of their copper­(II) complexes. Increasing amounts (with respect to the Pyr groups) of copper­(II) gave rise to different signals constituting the EPR spectra at room and low temperature corresponding to different coordinations of Cu²⁺ inside and outside the dendrimers. At low Cu²⁺ concentrations, CuN₄ coordination involving the DAB core is preferential for G3- and G5-Pyr, while G4-Pyr shows a CuN₃O coordination. CuN₂O₂ coordination into the external dendrimer layer was also contributing to G3- and G4-Pyr spectra. The structures of the proposed copper–dendrimer complexes were also shown. G4-Pyr displays unusual binding ability toward Cu­(II) ions. Mainly the remarkably low toxicity shown by G4-Pyr and its peculiar binding ability leads to a potential use in biomedical fields

Amphiphilic Dendritic Hydrogels with Carbosilane Nanodomains: Preparation and Characterization as Drug Delivery Systems

Carbosilane dendrimers are hyperbranched lipophilic scaffolds widely explored in biomedical applications. This work exploits, for the first time, the ability of these scaffolds to generate functional hydrogels with amphiphilic properties. The monodispersity and multivalency enable a precise synthetic control of the network, while the lipophilicity improves the compatibility with poorly soluble cargo. The first family of cleavable carbosilane dendrimers was designed for this purpose, overcoming one of the main drawbacks of these type of dendrimers. Biodegradable dendritic low-swelling hydrogels with aromatic nanodomains were easily prepared using the highly efficient click thiol–ene chemistry. Our studies through electron-paramagnetic resonance, molecular dynamics simulations, and experimental assays confirmed the impact of the carbosilane dendritic nanodomains in both the encapsulation and the release pattern of model drugs such as ibuprofen and curcumin. Curcumin-loaded hydrogels were further tested in in vitro assays against advanced prostate cancer cells. The dendritic hydrogels not only enabled drugs encapsulation; as proof of concept, ibuprofen was efficiently attached via fluoride-promoted esterification and was enzymatically cleaved, achieving a controlled release over time

Mechanism for Oxygen-Enhanced Photoconductivity in Rubrene: Electron Transfer Doping▽This publication involves research sponsored by the U.S. Department of Energy under grant no. DE FG02-04ER 46118 and Columbia University.

The oxygen-enhanced photoconductivity observed in crystalline rubrene is investigated using electron paramagnetic resonance (EPR) spectroscopy and steady-state and time dependent photoconductivity (PC) measurements. The EPR data indicate the presence of rubrene radical cation and oxygen radical anion pairs formed within the crystalline structure when rubrene is irradiated in the presence of oxygen. Radical lifetimes determined using EPR spectroscopy correlate well with transient PC data and provide strong evidence that the rubrene radical cation is the charge carrier responsible for enhanced conduction. This process is reversible, although photodegradation is also observed. The oxygen-enhanced PC of rubrene is thus explained by an electron transfer mechanism that generates radical cation “hole” carriers within the crystal via the oxygen acceptor

Endohedrally Functionalized Metal–Organic Cage-Cross-Linked Polymer Gels as Modular Heterogeneous Catalysts

The immobilization of homogeneous catalysts onto supports to improve recyclability while maintaining catalytic efficiency is often a trial-and-error process limited by poor control of the local catalyst environment and few strategies to append catalysts to support materials. Here, we introduce a modular heterogenous catalysis platform that addresses these challenges. Our approach leverages the well-defined interiors of self-assembled Pd12L24 metal–organic cages/polyhedra (MOCs): simple mixing of a catalyst-ligand of choice with a polymeric ligand, spacer ligands, and a Pd salt induces self-assembly of Pd12L24-cross-linked polymer gels featuring endohedrally catalyst-functionalized junctions. Semi-empirical calculations show that catalyst incorporation into the MOC junctions of these materials has minimal affect on the MOC geometry, giving rise to well-defined nanoconfined catalyst domains as confirmed experimentally using several techniques. Given the unique network topology of these freestanding gels, they are mechanically robust regardless of their endohedral catalyst composition, allowing them to be physically manipulated and transferred from one reaction to another to achieve multiple rounds of catalysis. Moreover, by decoupling the catalyst environment (interior of MOC junctions) from the physical properties of the support (the polymer matrix), this strategy enables catalysis in environments where homogeneous catalyst analogues are not viable, as demonstrated for the Au­(I)-catalyzed cyclization of 4-pentynoic acid in aqueous media

Endohedrally Functionalized Metal–Organic Cage-Cross-Linked Polymer Gels as Modular Heterogeneous Catalysts

The immobilization of homogeneous catalysts onto supports to improve recyclability while maintaining catalytic efficiency is often a trial-and-error process limited by poor control of the local catalyst environment and few strategies to append catalysts to support materials. Here, we introduce a modular heterogenous catalysis platform that addresses these challenges. Our approach leverages the well-defined interiors of self-assembled Pd12L24 metal–organic cages/polyhedra (MOCs): simple mixing of a catalyst-ligand of choice with a polymeric ligand, spacer ligands, and a Pd salt induces self-assembly of Pd12L24-cross-linked polymer gels featuring endohedrally catalyst-functionalized junctions. Semi-empirical calculations show that catalyst incorporation into the MOC junctions of these materials has minimal affect on the MOC geometry, giving rise to well-defined nanoconfined catalyst domains as confirmed experimentally using several techniques. Given the unique network topology of these freestanding gels, they are mechanically robust regardless of their endohedral catalyst composition, allowing them to be physically manipulated and transferred from one reaction to another to achieve multiple rounds of catalysis. Moreover, by decoupling the catalyst environment (interior of MOC junctions) from the physical properties of the support (the polymer matrix), this strategy enables catalysis in environments where homogeneous catalyst analogues are not viable, as demonstrated for the Au­(I)-catalyzed cyclization of 4-pentynoic acid in aqueous media