Π-Π Stacking Complex Induces Three-Component Coupling Reactions To Synthesize Functionalized Amines.

π-π stacking and ion-pairing interactions induced the generation of α-amino radicals under the irradiation of visible light without the requirement of an expensive photocatalyst. This strategy enabled the construction of functionalized amines via three-component coupling reactions with broad scope (we report >50 examples with an up to 90 % yield). This synthetic pathway also delivered complex functionalized amines with a very high yield. Quantum chemistry Density Functional Theory (DFT) calculations identified π-π stacked ionic complexes; time-dependent DFT was employed to simulate the absorption spectra, and nudged elastic band (NEB) methodology provided a possible interaction/reaction picture of the selected species.

Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation.

The recent advances in nanotechnology are revolutionizing preventive and therapeutic approaches to treating cardiovascular diseases. Controlling the extracellular matrix metalloproteinase (MMP) activation and expression in the failing human left ventricular myocardium represents a significant therapeutic target for heart disease. In this study, we used molecularly imprinting polymers (MIPs) to restore the correct balance between MMPs and their tissue inhibitors (TIMPs), and explored the potential of this technique exhaustively through chemical synthesis, physicochemical and biological characterizations, and computational chemistry methods. By molecular dynamics simulations based on classical force fields, we simulated the early stages of the imprinting process in solution disclosing the pivotal interaction established between the monomers and the MMP9 protein template. The average interaction energies of methacrylic acid (MAA) and poly (ethylene glycol) ethyl ether methacrylate (PEG) units were in the ranges 17-22 and 30-37 kcal/mol, respectively. At low coverage, the PEG monomers seemed firmly anchored to the protein surface and were not displaced by water, while only about 20% of MAA was replaced by water. The synthesis of MIPs was successfully with a monomer conversion higher than 99% and the production of spherical particles with average diameter of 344 ± 33 nm. HPLC analysis showed a specific recognition factor of MMP9 on MIPs of about 1.3. FT-IR Chemical Imaging confirmed the mechanisms necessary to generate a "selective memory" of the MIPs towards the enzyme. HPLC results indicated that the rebound amount of both TIMP1 and MMP2 to MIPs is lower than that of the template, showing a selectivity factor of 2.1 and 2.3, respectively. Preliminary tests on the effect of MIPs on H9C2 cells revealed that this treatment has no cytotoxic effects.

Exploring the mechanisms of drug-delivery by decorated ZnO nanoparticles through predictive ReaxFF molecular dynamics simulations.

Herein, we study the assembling of a drug delivery nanocarrier through reactive molecular dynamics simulations based on an appropriately tuned force field. First, we focus on the combination of the various components (all selected in agreement with experiments), namely nanoparticle (ZnO), functional chains (oleic acid), drug (carfilzomib), and solvent molecules (ethanol), and then on the ability of the assembled nanotool to release its cargo in a physiological environment (water). The simulation results reveal that reactivity is crucial for characterizing the stability of the functionalized ZnONP, its dynamics, and its interactions with lipid chains and drug molecules. The chains are stably chemisorbed on the ZnONP through monodentate or bidentate binding of the carboxyls to the Zn atoms (the hydrogens are released to the surface oxygens). Chains' self-interactions reinforce the lipid cover's stability and distribution on the ZnONP interface. The added drug migrates from the solution to the nano assembly and is captured by the lipids. The molecules are entrapped among the oleic acid chains and adsorbed on the uncoated regions of the nanoparticle surface, partially physisorbed or chemisorbed. The analysis of the simulations confirms that the supramolecular assembly is compact and stable in ethanol. However, upon injection into the water, the size of the aggregate gradually increases, and the lipids start to swell with the aqueous medium. The system evolves towards an unpacked structure where the chains are elongated, separated, and prone to release the cargo depending on local water activity and depth of cargo insertion. All the results agree with the literature confirming the reliability of our predictive computational procedure for disclosing the structure and dynamics of complex materials relevant to the medicinal chemistry field.

Lignin-Supported Heterogeneous Photocatalyst for the Direct Generation of H2O2 from Seawater.

The development of smart and sustainable photocatalysts is in high priority for the synthesis of H2O2 because the global demand for H2O2 is sharply rising. Currently, the global market share for H2O2 is around 4 billion US$ and is expected to grow by about 5.2 billion US$ by 2026. Traditional synthesis of H2O2 via the anthraquinone method is associated with the generation of substantial chemical waste as well as the requirement of a high energy input. In this respect, the oxidative transformation of pure water is a sustainable solution to meet the global demand. In fact, several photocatalysts have been developed to achieve this chemistry. However, 97% of the water on our planet is seawater, and it contains 3.0-5.0% of salts. The presence of salts in water deactivates the existing photocatalysts, and therefore, the existing photocatalysts have rarely shown reactivity toward seawater. Considering this, a sustainable heterogeneous photocatalyst, derived from hydrolysis lignin, has been developed, showing an excellent reactivity toward generating H2O2 directly from seawater under air. In fact, in the presence of this catalyst, we have been able to achieve 4085 µM of H2O2. Expediently, the catalyst has shown longer durability and can be recycled more than five times to generate H2O2 from seawater. Finally, full characterizations of this smart photocatalyst and a detailed mechanism have been proposed on the basis of the experimental evidence and multiscale/level calculations.

Chemo-enzymatic functionalized sustainable cellulosic membranes: Impact of regional selectivity on ions capture and antifouling behavior.

Most of the polymeric membranes synthesized for decentralization of polluted water use fossil-based components. Thus, there is an urgent need to create robust and tunable nano/micro materials for confidently designing efficient and selective polymeric water filters with guaranteed sustainability. We have chosen a robust high-grade microfibrillated cellulose (MFC) as the functional material and selectively tuned it via enzymatic catalysis, which led to the attachment of phosphate group at the C6 position, followed by esterification (fatty acid attachment at C2 and C3 carbon), which led to the increase in its antifouling properties. We have demonstrated the robustness of the functionalization by measuring the separation of various metal ions, and the antifouling properties by adding foulants, such as Bovine Serum Albumin (BSA) and cancerous cells to the test solutions. These prototype affinity MFC membranes represent the most promising type of next-generation high-performance filtration devices for a more sustainable society.

Thermal degradation of optical resonances in plasmonic nanoparticles.

The dependence of plasmon resonance excitations in ultrafine (3-7 nm) gold nanoparticles on heating and melting is investigated. An integrated approach is adopted, where molecular dynamics simulations of the spatial and temporal development of the atoms constituting the nanoparticles generate trajectories out of which system conformations are sampled and extracted for calculations of plasmonic excitation cross sections which then are averaged over the sample configurations for the final result. The calculations of the plasmonic excitations, which take into account the temperature- and size-dependent relaxation of the plasmons, are carried out with a newly developed Extended Discrete Interaction Model (Ex-DIM) and complemented by multilayered Mie theory. The integrated approach clearly demonstrates the conditions for suppression of the plasmons starting at temperatures well below the melting point. We have found a strong inhomogeneous dependence of the atom mobility in the particle crystal lattice increasing from the center to its surface upon the temperature growth. The plasmon resonance suppression is associated with an increase of the mobility and in the amplitude of phonon vibrations of the lattice atoms accompanied by electron-phonon scattering. This leads to an increase in the relaxation constant impeding the plasmon excitation as the major source of the suppression, while the direct contribution from the increase in the lattice constant and its chaotization at melting is found to be minor. Experimental verification of the suppression of surface plasmon resonance is demonstrated for gold nanoparticles on a quartz substrate heated up to the melting temperature and above.

Diverse Phases of Carbonaceous Materials from Stochastic Simulations.

Amorphous carbon systems are emerging to have unparalleled properties at multiple length scales, making them the preferred choice for creating advanced materials in many sectors, but the lack of long-range order makes it difficult to establish structure/property relationships. We propose an original computational approach to predict the morphology of carbonaceous materials for arbitrary densities that we apply here to graphitic phases at low densities from 1.15 to 0.16 g/cm3, including glassy carbon. This approach, dynamic reactive massaging of the potential energy surface (DynReaxMas), uses the ReaxFF reactive force field in a simulation protocol that combines potential energy surface (PES) transformations with global optimization within a multidescriptor representation. DynReaxMas enables the simulation of materials synthesis at temperatures close to experiment to correctly capture the interplay of activated vs entropic processes and the resulting phase morphology. We then show that DynReaxMas efficiently and semiautomatically produces atomistic configurations that span wide relevant regions of the PES at modest computational costs. Indeed, we find a variety of distinct phases at the same density, and we illustrate the evolution of competing phases as a function of density ranging from uniform vs bimodal distributions of pore sizes at higher and intermediate density (1.15 g/cm3 and 0.50 g/cm3) to agglomerated vs sparse morphologies, further partitioned into boxed vs hollow fibrillar morphologies, at lower density (0.16 g/cm3). Our observations of diverse phases at the same density agree with experiment. Some of our identified phases provide descriptors consistent with available experimental data on local density, pore sizes, and HRTEM images, showing that DynReaxMas provides a systematic classification of the complex field of amorphous carbonaceous materials that can provide 3D structures to interpret experimental observations.

New Mechanistic Insights into the Lignin ß-O-4 Linkage Acidolysis with Ethylene Glycol Stabilization Aided by Multilevel Computational Chemistry.

Acidolysis in conjunction with stabilization of reactive intermediates has emerged as one of the most powerful methods of lignin depolymerization that leads to high aromatic monomer yields. In particular, stabilization of reactive aldehydes using ethylene glycol results in the selective formation of the corresponding cyclic acetals (1,3-dioxolane derivatives) from model compounds, lignin, and even from softwood lignocellulose. Given the high practical utility of this method for future biorefineries, a deeper understanding of the method is desired. Here, we aim to elucidate key mechanistic questions utilizing a combination of experimental and multilevel computational approaches. The multiscale computational protocol used, based on ReaxFF molecular dynamics, represents a realistic scenario, where a typical experimental setup can be reproduced confidently given the explicit molecules of the solute, catalyst, and reagent. The nudged elastic band (NEB) approach allowed us to characterize the key intermolecular interactions involved in the reaction paths leading to crucial intermediates and products. The high level of detail obtained clearly revealed for the first time the unique role of sulfuric acid as a proton donor and acceptor in lignin ß-O-4 acidolysis as well as the reaction pathways for ethylene glycol stabilization, and the difference in reactivity between compounds with different methoxy substituents.

Optimization of a New Reactive Force Field for Silver-Based Materials.

A new reactive force field based on the ReaxFF formalism is effectively parametrized against an extended training set of quantum chemistry data (containing more than 120 different structures) to describe accurately silver and silver-thiolate systems. The results obtained with this novel representation demonstrate that the novel ReaxFF paradigm is a powerful methodology to reproduce more appropriately average geometric and energetic properties of metal clusters and slabs when compared to the earlier ReaxFF parametrizations dealing with silver and gold. ReaxFF cannot describe adequately specific geometrical features such as the observed shorter distances between the under-coordinated atoms at the cluster edges. Geometric and energetic properties of thiolates adsorbed on a silver Ag20 pyramid are correctly represented by the new ReaxFF and compared with results for gold. The simulation of self-assembled monolayers of thiolates on a silver (111) surface does not indicate the formation of staples in contrast to the results for gold-thiolate systems.

A close view of the organic linker in a MOF: structural insights from a combined 1H NMR relaxometry and computational investigation.

The organic linker in a metal organic framework (MOF) affects its adsorption behavior and performance, and its structure and dynamics play a role in the modulation of the adsorption properties. In this work, the combination of 1H nuclear magnetic resonance (NMR) longitudinal relaxometry and theoretical calculations allowed details of the structure and dynamics of the organic linker in the NH2-MIL-125 MOF to be obtained. In particular, fast field cycling (FFC) NMR, applied here for the first time on MOFs, was used to disclose the dynamics of the amino group and its electronic environment through the analysis of the 14N quadrupole relaxation peaks, observed in the frequency interval 0.5-5 MHz, at different temperatures from 25 to 110 °C. The line width of the peaks allowed a lower boundary on the rotational correlation time of the N-H bonds to be set, whereas relevant changes in the amplitudes were interpreted in terms of a change in the orientation of the 14N averaged electric field gradient tensor. The experimental findings were complemented by quantum chemistry calculations and classical molecular dynamics simulations.

Multivalent ion-induced re-entrant transition of carboxylated cellulose nanofibrils and its influence on nanomaterials' properties.

In this work, we identify and characterize a new intriguing capability of carboxylated cellulose nanofibrils that could be exploited to design smart nanomaterials with tuned response properties for specific applications. Cellulose nanofibrils undergo a multivalent counter-ion induced re-entrant behavior at a specific multivalent metal salt concentration. This effect is manifested as an abrupt increase in the strength of the hydrogel that returns upon a further increment of salt concentration. We systematically study this phenomenon using dynamic light scattering, small-angle X-ray scattering, and molecular dynamics simulations based on a reactive force field. We find that the transitions in the nanofibril microstructure are mainly because of the perturbing actions of multivalent metal ions that induce conformational changes of the nanocellulosic chains and thus new packing arrangements. These new aggregation states also cause changes in the thermal and mechanical properties as well as wettability of the resulting films, upon water evaporation. Our results provide guidelines for the fabrication of cellulose-based films with variable properties by the simple addition of multivalent ions.

Modeling generation and growth of iron oxide nanoparticles from representative precursors through ReaxFF molecular dynamics.

Detailed dynamical characterization of the mechanisms responsible for the formation and growth of iron oxide nanoparticles remains a significant challenge not only for experimental techniques but also for theoretical methodologies due to the nanoparticle size, long simulation times, and complexity of the environments. In this work, we have designed a fast computational protocol based on atomistic reactive molecular dynamics, which is capable of simulating the whole synthetic and proliferation process of the nanoparticles (greater than 10 nm) in a homogeneous medium from organometallic precursors. We have defined appropriate growth accelerating strategies based on the observed reactions, which consisted of the formation of Fe-O-Fe bridges, linking separate precursors, and Fe˙ and FeO˙ radicals. This reduced drastically the computational time allowing the simulation of NPs made of thousands of atoms (full nanometric range). We have identified the most probable reaction environments and summarized them under two distinct conditions: reductive and oxidative. The first one leads to the formation of nanoparticles with FeO stoichiometry typical of wustite, whereas the second one stabilizes stoichiometries between Fe3O4 (magnetite), and Fe2O3 (maghemite). In the latter case, the obtained NPs adopted, from the very early stages of the growth process, a cubic crystalline structure, typical of the oxidized FeOx bulk phases. The excellent agreement of our results with the experimental data demonstrates that the proposed protocol can provide a powerful predictive tool to describe structural features developed by the metal oxide nanoparticles and establish clear structure-property relationships.

Evaluation of nanocellulose interaction with water pollutants using nanocellulose colloidal probes and molecular dynamic simulations.

Atomic Force Microscope (AFM) probes were successfully functionalized with two types of nanocellulose, namely 2,2,6,6-tetramethylpiperidine-1-oxylradical (TEMPO)-mediated oxidized cellulose nanofibers (TOCNF) and cellulose nanocrystals (CNC) and used to study interfacial interactions of nanocellulose with Cu(II) ions and the Victoria blue B dye in liquid medium. TOCNF modified tip showed higher adhesion force due to adsorption of Cu(II) ions and dye molecules compared to CNC ones. Exploring the adsorption properties through classical reactive molecular dynamics simulations (ReaxFF) at the atomic scale confirmed that the Cu(II) ions promptly migrated and adsorbed onto the nanocelluloses through the co-operative chelating action of carboxyl and hydroxyl species. The adsorbed Cu(II) ions showed the tendency to self-organize by forming nano-clusters of variable size, whereas the dye adopted a flat orientation to maximize its adsorption. The satisfactory agreement between the two techniques suggests that functionalized AFM probes can be successfully used to study nanocellulose surface interactions in dry or aqueous environment.

Nanocellulose/graphene oxide layered membranes: elucidating their behaviour during filtration of water and metal ions in real time.

The deposition of a thin layer of graphene oxide onto cellulose nanofibril membranes, to form CNF-GO layered-composite membranes, dramatically enhances their wet-mechanical stability, water flux and capacity to adsorb water pollutants (P. Liu, C. Zhu and A. P. Mathew, J. Hazard. Mater., 2019, 371, 484-493). In this work, we studied in real time the behavior of these layered membranes during filtration of water and metal ion solutions by means of in situ SAXS and reactive molecular dynamics (ReaxFF) computational simulations. SAXS confirms that the GO layers limit the swelling and structural deformations of CNFs during filtration of aqueous solutions. Moreover, during filtration of metal ion solutions, the connection of the CNF-GO network becomes highly complex mass-fractal like, with an increment in the correlation length. In addition, after ion adsorption, the SAXS data revealed apparent formation of nanoparticles during the drying stage and particle size increase as a function of time during drying. The molecular dynamics simulations, on the other hand, provide a deep insight into the assembly of both components, as well as elucidating the motion of the metal ions that potentially lead to the formation of metal clusters during adsorption, confirming the synergistic behavior of GO and CNFs for water purification applications.

Structure and dynamics of gold nanoparticles decorated with chitosan-gentamicin conjugates: ReaxFF molecular dynamics simulations to disclose drug delivery.

With the aim of designing an efficient procedure for producing biocompatible drug delivery systems based on nanoparticle carriers for in situ controlled antibiotic release, we have defined a novel computational approach resorting to a reactive force field capable of realistically describing hybrid systems. The modeling procedure was focused on well-known components, namely gold nanoparticles, citrate, chitosan and gentamicin, and the experiments tuned on purpose. On the one hand, gold nanoparticles were synthesized, fuctionalized with chitosan, loaded with gentamicin and characterized by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), UV-visible (UV-vis) spectroscopy, and Fourier transform infrared spectroscopy (FTIR). On the other hand, an effective model of a functionalized gold nanoparticle was created and its structure and dynamics were explored by classical reactive molecular dynamics simulations in solution based on the ReaxFF atomistic description. The structure, dynamics and drug release were reproduced realistically disclosing the motion of all the molecular components, their adsorption on the metal support, desorption, intermolecular interactions and self-assembly. The system size was very close to the experimental conditions and all the calculations could efficiently identify the most probable binding modes, the locations of the adsorbed molecules, the characteristic arrangements of the chains and the effects due to the surrounding environment. The role played by the substrate and water molecules in the releasing process was described in detail. In line with the literature it was found that the antibiotic activity was preserved and the drug release from the carrier could be tuned by changing the chitosan/getamicin weight ratio and the deposition pattern of the adsorbed layers.

Core Shell Investigation of 2-nitroimidazole.

Tunability and selectivity of synchrotron radiation have been used to study the excitation and ionization of 2-nitroimidazole at the C, N, and O K-edges. The combination of a set of different measurements (X-ray photoelectron spectroscopy, near-edge photoabsorption spectroscopy, Resonant Auger electron spectroscopy, and mass spectrometry) and computational modeling have successfully disclosed local effects due to the chemical environment on both excitation/ionization and fragmentation of the molecule.

pH-dependent X-ray Photoelectron Chemical Shifts and Surface Distribution of Cysteine in Aqueous Solution.

The distribution and protonation states of amino acids in water droplets are of considerable concern in studies on the formation of clouds in the atmosphere as well as in many biological contexts. In the present work we use the amino acid cysteine as a prototypical example and explore the protonation states of this molecule in aqueous solution, which are strongly affected by the acidity of the environment and also can show different distributions between surface and bulk. We use a combination of X-ray photoelectron chemical shift measurements, density functional theory calculations of the shifts, and reactive force field molecular dynamics simulations of the underlying structural dynamics. We explore how the photoelectron spectra distinctly reflect the different protonation states that are generated by variation of the solution acidity and how the distribution of these protonation states can differ between bulk and surface regions. At specific pH values, we find that the distribution of the cysteine species at the surface is quite different from that in bulk, in particular, for the appearance in the surface region of species which do not exist in bulk. Some ramifications of this finding are discussed.

Modeling Nucleation and Growth of ZnO Nanoparticles in a Low Temperature Plasma by Reactive Dynamics.

The very first stages of nucleation and growth of ZnO nanoparticles in a plasma reactor are studied by means of a multiscale computational paradigm where the DFT-GGA approach is used to evaluate structure and electronic energy of small (ZnO) N clusters ( N ≤ 24) that are employed as a training set (TS) for the optimization of a Reactive Force Field (ReaxFF). Reactive Molecular Dynamics (RMD) simulations based on this tuned ReaxFF are carried out to reproduce nucleation and growth in a realistic environment. Inside the reaction chamber the temperature is around 1200 K, and the zinc atoms are oxidized in an oxygen-rich atmosphere at high pressure (about 20 atm), whereas in the quenching chamber where the temperature is lower (about 800 K) the ZnO embryo-nanoclusters are grown. The main processes ruling gas-phase nucleation and growth of ZnO nanoclusters are identified and discussed together with the dependence of the inception time and average stoichiometry of nanoclusters of different size on the composition of precursor material and physical parameters.

Experimental and theoretical elucidation of catalytic pathways in TiO2-initiated prebiotic polymerization.

The tendency of glycine to form polymer chains on a rutile(110) surface under wet/dry conditions (dry-wet cycles at high temperature) is studied through a conjunction of surface sensitive experimental techniques and sequential periodic multilevel calculations that mimics the experimental procedures with models of decreasing complexity and increasing accuracy. X-ray photoemission spectroscopy (XPS) and thermal desorption spectroscopy (TDS) experimentally confirmed that the dry-wet cycles lead to Gly polymerization on the oxide support. This was supported by all the theoretical characterizations. First, classical reactive molecular dynamics (MD) simulations based on the ReaxFF approach were used to reproduce the adsorption of the experimental glycine solution droplets sprayed onto an oxide support and to identify the most probable arrangement of the molecules that triggered the polymerization mechanisms. Then, quantum chemistry density functional tight binding (DF-TB) MDs and static density functional theory (DFT) calculations were carried out to further explore favorable configurations and to evaluate the energy barriers of the most promising reaction pathways for the peptide bond-formation reactions. The results confirmed the fundamental role played by the substrate to thermodynamically and kinetically favor the process and disclosed its main function as an immobilizing agent: the molecules accommodated in the surface channels close to each other were the ones starting the key events of the dimerization process and the most favorable mechanism was the one where a water molecule acted as a proton exchange mediator in the condensation process.

Design of ultrathin hybrid membranes with improved retention efficiency of molecular dyes.

Ultrathin layers of 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) Oxidized Cellulose Nanofibers (TOCNF) embedded with Graphene Oxide nanosheets (GOs) in different ratios were built, via the blade coating technique, on a polyvinylidene difluoride (PVDF) substrate to obtain superior membranes for separating water pollutants from aqueous media. Cellulose nanofiber-graphene oxide hybrid materials have shown a great potential for water purification due to their active microporous structure with extended areas rich in negatively charged carboxyl functional groups capable of adsorbing positively charged contaminants efficiently. In contrast to the pristine free-standing TOCNF films, which are completely impermeable, the ultrathin (68 nm thick) hybrid coating with a 100 : 1 TOCNF : GO ratio showed a stable water permeability (816 ± 3.4 L m-2 h-1 bar-1) higher than that of common polymeric membranes, and a very efficient size selectivity during filtration of water contaminated by various types of dyes. The membranes had high retention efficiency (82-99%) for dyes with hydrated radii greater than ≈0.5 nm due to the favorable combination of electrostatic/hydrophobic interactions with the hybrid matrices and steric entrapment controlled by the pore size. This was confirmed by theoretical calculations that revealed both the structure and dynamic behavior of the dyes in the complex environment of the membranes.