Modeling polyzwitterion-based drug delivery platforms: A perspective of the current state-of-the-art and beyond

Drug delivery platforms are anticipated to have biocompatible and bioinert surfaces. PEGylation of drug carriers is the most approved method since it improves water solubility and colloid stability and decreases the drug vehicles’ interactions with blood components. Although this approach extends their biocompatibility, biorecognition mechanisms prevent them from biodistribution and thus efficient drug transfer. Recent studies have shown (poly)zwitterions to be alternatives for PEG with superior biocompatibility. (Poly)zwitterions are super hydrophilic, mainly stimuli-responsive, easy to functionalize and they display an extremely low protein adsorption and long biodistribution time. These unique characteristics make them already promising candidates as drug delivery carriers. Furthermore, since they have highly dense charged groups with opposite signs, (poly)zwitterions are intensely hydrated under physiological conditions. This exceptional hydration potential makes them ideal for the design of therapeutic vehicles with antifouling capability, i.e., preventing undesired sorption of biologics from the human body in the drug delivery vehicle. Therefore, (poly)zwitterionic materials have been broadly applied in stimuli-responsive “intelligent” drug delivery systems as well as tumor-targeting carriers because of their excellent biocompatibility, low cytotoxicity, insignificant immunogenicity, high stability, and long circulation time. To tailor (poly)zwitterionic drug vehicles, an interpretation of the structural and stimuli-responsive behavior of this type of polymer is essential. To this end, a direct study of molecular-level interactions, orientations, configurations, and physicochemical properties of (poly)zwitterions is required, which can be achieved via molecular modeling, which has become an influential tool for discovering new materials and understanding diverse material phenomena. As the essential bridge between science and engineering, molecular simulations enable the fundamental  understanding of the encapsulation and release behavior of intelligent drug-loaded (poly)zwitterion nanoparticles and can help us to systematically design their next generations. When combined with experiments, modeling can make quantitative predictions. This perspective article aims to illustrate key recent developments in (poly)zwitterion-based drug delivery systems. We summarize how to use predictive multiscale molecular modeling techniques to successfully boost the development of intelligent multifunctional (poly)zwitterions-based systems.</p

Oxygen evolution and reduction on Fe-doped NiOOH: influence of solvent, dopant position and reaction mechanism

The oxygen evolution reaction (OER) is the limiting factor in an electrolyzer and the oxygen reduction reaction (ORR) the limiting factor in a fuel cell. In OER, water is converted to O2 and H+/e- pairs, while in ORR the reverse process happens to form water. Both reactions and their efficiency are important enablers of a hydrogen economy where hydrogen will act as a fuel or energy storage medium. OER and ORR can both be described assuming a 4-step electrochemical mechanism with coupled H+/e- transfers between 4 intermediates (M-*, M-OH, M=O, M-OOH, M = active site). Previously, it was shown that an unstable M-OOH species can equilibrate to an MOO species and a hydrogenated acceptor site (M-OOH/eq), enabling a bifunctional mechanism. Within OER, the presence of Fe within an NiOOH acceptor site was found to be beneficial to lower the required overpotential (Vandichel et al. Chemcatchem, 2020, 12 (5), 1436-1442). In this work, we present the first proof-of-concept study of various possible mechanisms (standard and bifunctional ones) for OER and ORR, i.e. we include now the active edge sites and hydrogen acceptor sites in the same model system. Furthermore, we consider water as solvent to describe the equilibration of the M-OOH species to M-OOH/eq, a crucial step that enables a bifunctional route to be operative. Additionally, different single Fe-dopant positions in an exfoliated NiOOH model are considered and four different reaction schemes are studied for OER and the reverse ORR process. The results are relevant in alkaline conditions, where the studied model systems are stable. Certain Fe-dopant positions result in active Ni-edge sites with very low overpotentials provided water is present within the model system

Oxygen evolution on metal‐oxy‐hydroxides: beneficial role of mixing Fe, Co, Ni explained via bifunctional edge/acceptor route

Oxygen evolution (OER) via mixed metal oxy hydroxides [M(O)(OH)] may take place on a large variety of possible active sites on the actual catalyst. A single site computational description assumes a 4-step electrochemical mechanism with coupled H+/e- transfers between 4 intermediates (M-*, M-OH, M=O, M-OOH). We also consider bifunctional routes, in which an unstable M-OOH species converts via a proton shuttling pathway to a thermodynamically more favourable bare M-* site, O2 and a hydrogenated acceptor site; the acceptor site takes up the proton forming a hydrogenated acceptor site after recombination with an electron from the catalyst material. Here, we combine pure metal γM(O)(OH) edge sites (M = Fe, Co, Ni) with as proton-acceptor sites different threefold coordinated oxygens on β-(M,M’)(O)(OH) terraces (M,M’ = Fe, Co, Ni). The acceptor sites on these terraces have of a M’2MO motif. Our combinatorial study results in a ranking of their bifunctional OER activity on a 3D-volcano plot. Via various bi- and tri-metallic oxy hydroxide combinations, we show that their excellent experimental OER activity results from bifunctionality and provide a roadmap to construct innovative low overpotential OER catalyst

Computational unravelling of cathodic hydride formation on palladium surfaces

Palladium (Pd) is well-known for its role in catalyzing hydrogen-based reduction reactions, owing to its excellent catalytic activity and hydrogen storage ability. Its surface and subsurface structures under electrochemical conditions are vital in understanding the hydrogen evolution reaction (HER) mechanism at the Pd cathodes where the most active sites are located on ‘in situ’ formed Pd-hydride layers. In this work, we investigate the process of Pd-hydride formation as well as the step-by-step formation and stability of Pd-hydride/Pd interfaces under electrochemical conditions using first-principles calculations. Our results reveal that among the low-indexed surfaces (111), (110) and (100), the (111) surface is expected to be the most dominant surface in a Pd nanostructure in addition to being the most preferred surface for hydrogen adsorption. Based on calculated Pourbaix diagrams, we can identify the relevant regions close to the equilibrium electrode potential and pH for proton electroreduction and hydrogen evolution, where the Pd surfaces start to be covered by hydrogen adatoms, and when the electrode potential is decreased, there are clear thermodynamic indications for more and more subsurface hydride layers. Overall, the results provide insights into the stability and formation of hydrogen containing Pd surfaces, forming PdH/Pd type interfaces. Our idealized model systems are a first step towards elucidation of relevant active sites on Pd.</p

Enhancing magnesium-ion storage in a Bi−Sn anode through dual - phase engineering

Magnesium-ion batteries (MIBs) are a “beyond Li-ion” technology that are hampered by Mg metal reactivity, which motivates the development of anode materials such as tin (Sn) with high theoretical capacity (903 mAh g−1 ). However, pure Sn is inactive for Mg2+ storage. Herein, Mg alloying with Sn is enabled within dual-phase Bi−Sn anodes, where the optimal composition (Bi66.5Sn33.5) outperformed single-phase Bi and Sn electrodes to deliver high specific capacity (462 mAh g−1 at 100 mA g−1 ), good cycle life (84% after 200 cycles), and significantly improved rate capability (403 mAh g−1 at 1000 mA g−1 ). Density functional theory (DFT) calculations revealed that Mg alloys first with Bi and the subsequent formation of the Mg3Bi2//Sn interfaces is energetically more favorable compared to the individual Mg3Bi2 and Sn phases. Mg insertion into Sn is facilitated when Mg3Bi2 is present. Moreover, dealloying Mg from Mg3Bi2:Mg2Sn systems requires the creation of Mg vacancies and subsequent Mg diffusion. Mg vacancy creation is easier for Mg2Sn compared to Mg3Bi2, while the latter has slightly lower activated Mg-diffusion pathways. The computational findings point toward easier magnesiation/demagnesiation for BiSn alloys over pure Bi or pure Sn, corroborating the superior Mg storage performance of Bi−Sn electrodes over the corresponding single-phase electrodes.</p

Peripherally "tertiary butyl ester" functionalized bipyridine cored dendrons: From synthesis, characterization to molecular dynamic simulation study

In this research, we have designed and synthesized a series of novel bipyridine cored poly (benzyl-ether) dendrons containing tertiary butyl esters at their periphery. The molecular structures of the synthesized dendrons were characterized via NMR and mass spectrometry. We investigated the solvent dependent hydrodynamic size of the synthesized dendrons in dimethyl sulfoxide (DMSO) and water using dynamic light scattering (DLS) experiments and the water contact angle of the dendrons were also analyzed. To understand the structure and solvation behaviour of these novel dendrons at the atomistic level, we performed all-atom molecular dynamics (MD) simulations. The behaviour, configuration, and size of the dendrons in DMSO and water were studied through the calculation of the radius of gyration (Rg), radial distribution function g(r), and solvent accessible surface area (SASA). The modelling results confirmed the experimental observations that DMSO is a better solvent than water for the dendrons as it results in a more unfolded molecular structure. Based on the above experimental results, these dendritic polymer can be an excellent candidate for multifunctional theranostics platforms.</p

Computational surface pourbaix diagrams to unravel cathodic hydride formation on defective palladium surfaces

Defects, both intrinsic and hydrogen-induced, are commonplace in electrochemical processes, particularly in catalysis where hydrogen can penetrate the catalysts and influence chemical reactions. Palladium (Pd), renowned for its high hydrogen permeability, forms defects upon exposure to hydrogen. Herein, we investigate various defective Pd-surfaces containing missing row, vacancy, and adatom defects, and their interplay with hydrogen atoms to enhance our understanding of Pd-based catalysts during hydrogenation reactions or with Pd as a cathode. Low-index defective surfaces and various hydrogen (H) coverages are explored to construct surface Pourbaix diagrams (SPD) and study their H-termination at specific pH and potential. The SPDs show increased hydrogen adsorption upon lowering the electrode potential. The stability of defective surfaces follows Pd’(110) > Pd’(100) > Pd’(111), in contrast to the stability trend observed for pristine surfaces, Pd(111) > Pd(100) > Pd (110). This reversal is attributed to the tendency of ‘less stable’ open surfaces, such as Pd(110), to reconstruct, or be stabilized by hydrogen. Our study emphasizes the importance of hydrogen sublayers in stabilizing H-covered defective surfaces, which facilitates the formation of Pd vacancies in the sublayers. Our work is essential to advance catalysis and surface science, as it provides valuable insights into material restructuring under elec?trocatalytic environments.</p

Surprisingly low reactivity of manganese oxide toward water oxidation in an ultra-pure electrolyte under alkaline conditions

So far, many studies on the oxygen-evolution reaction (OER) by Mn oxides have been focused on activity; however, the identification of the best performing active site and corresponding catalytic cycles is also of critical importance. Herein, the real intrinsic activity of layered Mn oxide toward OER in Fe/Ni-free KOH is studied for the first time. At pH ≈ 14, the onset of OER for layered Mn oxide in the presence of Fe/Ni-free KOH happens at 1.72 V (vs reversible hydrogen electrode (RHE)). In the presence of Fe ions, a 190 mV decrease in the overpotential of OER was recorded for layered Mn oxide as well as a significant decrease (from 172.8 to 49 mV/decade) in the Tafel slope. Furthermore, we find that both Ni and Fe ions increase OER remarkably in the presence of layered Mn oxide, but that pure layered Mn oxide is not an efficient catalyst for OER without Ni and Fe under alkaline conditions. Thus, pure layered Mn oxide and electrolytes are critical factors in finding the real intrinsic activity of layered Mn oxide for OER. Our results call into question the high efficiency of layered Mn oxides toward OER under alkaline conditions and also elucidate the significant role of Ni and Fe impurities in the electrolyte in the presence of layered Mn oxide toward OER under alkaline conditions. Overall, a computational model supports the conclusions from the experimental structural and electrochemical characterizations. In particular, substitutional doping with Fe decreases the thermodynamic OER overpotential up to 310 mV. Besides, the thermodynamic OER onset potential calculated for the Fe-free structures is higher than 1.7 V (vs RHE) and, thus, not in the stability range of Mn oxides.</p

Anticancer potential of dendritic poly(aryl ether) substituted polypyridyl ligands based ruthenium(II)- coordination entities

1. Synthesis and characterizations 1.1. Synthesis of Ruthenium(II)-cored metallodendrimers The synthesis of [Ru(bpy)2Gn-bpy]Cl2 complexes RuG0, RuG1 and RuG2 involves the reaction of [Ru(bpy)2Cl2.2H2O]Cl2 and corresponding Gn-bpy ligands under inert atmosphere. The obtained residue was purified by column chromatography to obtain the complexes [Ru(bpy)2G0-bpy]Cl2 (RuG0), [Ru(bpy)2G1-bpy]Cl2 (RuG1) and [Ru(bpy)2G2-bpy]Cl2 (RuG2). 1.1.2. Synthesis of 4,4'-bis[3'',5''-bis(2-(tert-butoxy)-2-oxoethoxy) benzyloxy]2,2'- bipyridine-bis(2,2’-bipyridine) Ruthenium (II) (RuG0) The complex RuG0 was obtained by the reaction of [Ru(bpy)2Cl2] and G0-bpy in 1:1.05 ratio. The crude product was purified by column chromatography (SiO2/dichloromethane: methanol 20:1 mixture); the product was obtained as red solid, Yield 70%.</p

Synthesis of colloidal WSe2 nanocrystals: polymorphism control by precursor-ligand chemistry

Syntheses of transition-metal dichalcogenides (TMDs) using colloidal-chemistry approaches are gaining signifi cant interest in recent years, as these methods enable the morphology and properties of the nanocrystals to be tuned for targeted applications. In this work, by only varying the ligand used during synthesis, we synthesized nanoflowers with oleic acid (OA) and 1T′ phase dominated WSe2 nanosheets with oleylamine (OLA). WSe2 nanocrystals show slower rate of formation for the metastable 1T′ phase. Surface chemistry analyses of the synthesized nanocryst als by solution NMR establish that neither of the ligands bind strongly to the surface of nanocrystals but are in a dynamic coordination with the WSe2 surface. A further examination of the coordination of tungsten hexacarbonyl (W(CO)6) with the respective ligands confirms that W(CO)6 decomposes in OA, losing its octahedral symmetry, which leads to fast reactivity in the flask. In contrast to this, W(CO)6 reacts with OLA to form a new complex, which leads to slower reactivity and crystallization of the synthesized nanocrystals in the octahedral 1T′ phase. These insights into the influence of precursor-ligand chemistry on reaction outcome and the peculiar surface chemistry of colloidal TMD nanocrystals will be instrumental in developing future colloidal TMD nanocrystals