Computer simulations on oxidative stress-induced reactions in SARS-CoV-2 spike glycoprotein: a multi-scale approach

Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in a misbalance of antioxidant and pro-oxidants species, is the common denominator of diseases considered as a risk factor for SARS-CoV-2 lethality. Indeed, reactive oxygen species caused by oxidative stress have been related to many virus pathogenicity. In this work, simulations have been performed on the receptor binding domain of SARS-CoV-2 spike glycoprotein to study what residues are more susceptible to be attacked by ·OH, which is one of the most reactive radicals associated to oxidative stress. The results indicate that isoleucine (ILE) probably plays a crucial role in modification processes driven by radicals. Accordingly, QM/MM-MD simulations have been conducted to study both the ·OH-mediated hydrogen abstraction of ILE residues and the induced modification of the resulting ILE radical through hydroxylation or nitrosylation reactions. All in all, in silico studies show the importance of the chemical environment triggered by oxidative stress on the modifications of the virus, which is expected to help for foreseeing the identification or development of antioxidants as therapeutic drugs. Graphic abstrac

Surviving mass extinctions through biomineralized DNA

Even in the worst of conditions, such as those which occurred during mass extinction events, life on Earth never totally stopped. Aggressive chemical and physical attacks able to sterilize or poison living organisms occurred repeatedly. Surprisingly, DNA was not degraded, denatured or modified to the point of losing the capability of transferring the genetic information to the next generations. After the events of mass extinction life was able to survive and thrive. DNA was passed on despite being an extremely fragile biomolecule. The potential implications of hydroxyapatite protection of DNA are discussed in this Concept article including how DNA acts as a template for hydroxyapatite (HAp) formation, how cell death can trigger biomineralization, and how DNA can be successfully released from HAp when the conditions are favorable for life.Peer ReviewedPostprint (published version

Aromatic ionene topology and counterion-tuned gelation of acidic aqueous solutions

Unusual gelation of acidic solutions was achieved using polycations bearing quaternary ammonium moieties. These ionene polymers are based on a disubstituted phenylene dibenzamide core, which allows the construction of different topomers (i.e. ortho-1, meta-2 and para-3). The topology of the polymers was found to play a key role on their aggregation behaviour both in pure water and in a variety of aqueous acidic solutions leading to the formation of stable acidic gels. Specifically, ortho-1 showed superior gelation ability than the analogues meta-2 and para-3 in numerous solutions of different pH and ionic strengths. Lower critical gelation concentrations, higher gel-to-sol transition temperatures and faster gelation were usually observed for ortho-1 regardless the solvent system. Detailed computational molecular dynamic simulations revealed a major role of the counterion (Cl-) and specific polymer¿polymer interactions. In particular, hydrogen bonds, N–H¿p interactions and intramolecular p–p stacking networks are distinctive in ortho-1. In addition, counterions located at internal hydration regions also affect to such polymer¿polymer interactions, acting as binders and, therefore, providing additional stability.Peer ReviewedPostprint (published version

Modeling nanosized single molecule objects: dendronized polymers adsorbed onto mica

We attempt to provide direct evidence for the suggested behavior of dendronized polymers as molecular objects (i.e., single shape persistent macromolecules). For this purpose, the microscopic structure of dendronized polymers adsorbed onto mica has been investigated using atomistic molecular dynamics simulations. We find that the shape of the second to fourth generation dendronized polymers is basically kept upon adsorption due to substantial backfolding within their interior. The fluctuation strength of the polymer backbones, which is seen to decrease with increasing generation, also indicates that these individual macromolecules exhibit molecular object behavior in the nanosize rangePostprint (published version

Effects of hydroxyapatite (0001) Ca2+/Mg2+ substitution on adsorbed D-ribose ring puckering

Advanced Molecular Dynamics (MD) simulation protocols have been used to assess the ring puckering of cyclic D-ribose when the sugar is adsorbed on the most stable (0001) facet of calcium hydroxyapatite (HAp). In addition, sugar¿mineral interactions, which are crucial for transfection processes and prebiotic chemistry, have been studied for systems in which the Ca2+ ions of the above mentioned HAp facet were totally or partially replaced by Mg2+. The latter replacement is spatially and quantitatively limited and has been found to cause important alterations in the conformational behavior of D-ribose that are similar to those suffered in hairpin RNA from A to B helical structures. Accordingly, replacement of Ca2+ by Mg2+ has a dramatic effect on the functionality of the nucleic acid. These changes have been related to both the substitution site on the surface and the amount of ions. Our results show that when replacement by Mg2+ occurs in OH--coordinated Ca2+ ions, Mg2+¿D-ribose interactions are strong enough to prevent the interactions between the hydroxyl groups of the sugar and the remaining Ca2+ ions.Peer ReviewedPostprint (published version

Electrochemical activation for sensing of three-dimensional-printed poly(lactic acid) using low-pressure plasma

Integrated electrochemical sensors in which plasma-treated poly(lactic acid) (PLA) single material acts as both selective coating layer and electrochemical transductor (electrode) are prepared. Thus, three-dimensional-printed PLA specimens are transformed into electroresponsive material by applying a low-pressure gas plasma treatment with three different gases: N2, O2, and air (79% N2¿+¿21% O2). Although all treated samples are able to electrochemically detect dopamine, the one derived from the treatment of low-pressure O2 plasma exhibits the best performance as a sensor. Finally, cell adhesion assays demonstrate that the cell viability is higher for plasma-treated PLA modified than for pristine PLA, making the former a promising, versatile, and powerful electroresponsive platform for diverse applications in biomedicine.Peer ReviewedPostprint (published version

On the modeling of aggregates of an optically active regioregular polythiophene

The conformational properties of the optically active regioregular poly[(R)-3-(4-(4-ethyl-2-oxazolin-2-yl) phenyl) thiophene] (PEOPT) were explored by molecular dynamics on a single chain using several solvents of increasing polarity. Furthermore, their aggregate formation was studied over a wide range of temperatures using a replica exchange molecular dynamics simulation providing simulation data representative of the equilibrium behaviour of their aggregates. Results show a clear tendency of PEOPT to keep a syn–gauche conformation between continuous backbone thiophene rings favouring a bent chain structure in solvent. After studying their aggregation behaviour in acetonitrile, a strong tendency to pack stabilizing structures that reinforce the chirality of the polymer, in concordance with experimental data, was found. Two different aggregated structures were observed depending on oligomer length, a self-assembled helical aggregate based on stacked octamers and a bent double helix aggregate in large oligomers.Postprint (published version

Analysis of nitrogen fixation by a catalyst capable of transforming N2, CO2 and CH4 into amino acids under mild reactions conditions

The processes related to the fixation of nitrogen ina catalyst able to produce glycine and alanine from a N2, CO2and CH4gas mixture at mild reaction conditions have been studied by combining experimental and theoretical investigations.Results have allowed to understand the role of different elements of the catalyst, which is constituted by permanently polarized hydroxyapatite (p-HAp), zirconia, and aminotris(methylenephosphonic acid)(ATMP). ATMP attractsN2moleculestowards the surface,maintainingthem close to the zirconiaand p-HAp componentsthatare the most active from a catalytic point of view. On the other hand, the associative mechanismisthermodynamicallyfavouredunder mild reaction conditionswith respect to the dissociative one,whichis limited by the barrier associated to the N–Nbondcleavage. Because this reaction mechanism is similar to that employed in the nitrogen fixation bynitrogenase enzymes, thesefindingsprovide an opportunity to designnew bioinspired catalystsPostprint (author's final draft

Dissolving hydroxyolite: a DNA molecule into its hydroxyapatite mold

In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that controls its dissolution in acidic environments remains unclear. Knowledge of such a process is highly desirable to provide better understanding of different pathologies, as for example osteoporosis, and of the HAp potential as vehicle for gene delivery to replace damaged DNA. In this work, the mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has been investigated at the atomistic level using computer simulations. For this purpose, four consecutive (multi-step) molecular dynamics simulations, involving different temperatures and proton transfer processes, have been carried out. Results are consistent with a polynuclear decalcification mechanism in which proton transfer processes, from the surface to the internal regions of the particle, play a crucial role. In addition, the DNA remains protected by the mineral mold and transferred proton from both temperature and chemicals. These results, which indicate that biomineralization imparts very effective protection to DNA, also have important implications in other biomedical fields, as for example in the design of artificial bones or in the fight against osteoporosis by promoting the fixation of Ca2+ ions.Peer ReviewedPostprint (published version

Hydroxyapatite with permanent electrical polarization: preparation, characterization, and response against inorganic adsorbates

Permanently polarized hydroxyapatite (HAp) particles have been prepared by applying a constant DC of 500 V at 1000¿°C for 1 h to the sintered mineral. This process causes important chemical changes, as the formation of OH- defects (vacancies), the disappearance of hydrogenophosphate ions at the mineral surface layer, and structural variations reflected by the increment of the crystallinity. As a consequence, the electrochemical properties and electrical conductivity of the polarized mineral increase noticeably compared with as-prepared and sintered samples. Moreover, these increments remain practically unaltered after several months. In addition, permanent polarization favours significantly the ability of HAp to adsorb inorganic bioadsorbates in comparison with as-prepared and sintered samples. The adsorbates cause a significant increment of the electrochemical stability and electrical conductivity with respect to bare polarized HAp, which may have many implications for biomedical applications of permanently polarized HAp.Peer ReviewedPostprint (author's final draft