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The biological activity of proteins is partly due to their secondary structures and conformational states. Peptide chains are rather flexible so that finding ways inducing protein folding in a well-defined state is of great importance. Among the different constraint techniques, the interaction of proteins with inorganic surfaces is a fruitful strategy to stabilize selected folded states. Surface-induced peptide folding can have potential applications in different biomedicine areas, but it can also be of fundamental interest in prebiotic chemistry since the biological activity of a peptide can turn-on when folded in a given state. In this work, periodic quantum mechanical simulations (including implicit solvation effects) at the PBE-D2* level have been carried out to study the adsorption and the stability of the secondary structures (α-helix and β-sheet) of polypeptides with different chemical composition (

Collagen proteins are spread in almost every vertebrate's tissue with mechanical function. The defining feature of this fundamental family of proteins is its well-known collagen triple-helical domain. This helical domain can have different geometries, varying in helical elongation and interstrands contact, as a function of the amino acidic composition. The helical geometrical features play an important role in the interaction of the collagen protein with cell receptors, but for the vast majority of collagen compositions, these geometrical features are unknown. Quantum mechanical (QM) simulations based on the density functional theory (DFT) provide a robust approach to characterize the scenario on the collagen composition-structure relationships. In this work, we analyze the role of the adopted computational method in predicting the collagen structure for two purposes. First, we look for a cost-effective computational approach to apply to a large-scale composition-structure analysis. Second, we attempt to assess the robustness of the predictions by varying the QM methods. Therefore, we have run geometry optimization on periodic models of the collagen protein using a variety of approaches based on the most commonly used DFT functionals (PBE, HSE06, and B3LYP) with and without dispersion correction (D3ABC). We have coupled these methods with several different basis sets, looking for the highest accuracy/cost ratio. Furthermore, we have studied the performance of the composite HF-3c method and the semiempirical GFN1-xTB method. Our results identify a computational recipe that is potentially capable of predicting collagen structural features in line with DFT simulations, with orders of magnitude reduced computational cost, encouraging further investigations on the topic.

The binding energies (BE) of molecules on the interstellar grains are crucial in the chemical evolution of the interstellar medium (ISM). Both temperature programmed desorption (TPD) laboratory experiments and quantum chemistry computations have often provided, so far, only single values of the BE for each molecule. This is a severe limitation, as the ices enveloping the grain mantles are structurally amorphous, giving rise to a manifold of possible adsorption sites, each with different BEs. However, the ice amorphous nature prevents the knowledge of structural details, hindering the development of a common accepted atomistic icy model. In this work, we propose a computational framework that closely mimics the formation of the interstellar grain mantle through a water by water accretion. On that grain, an unbiased random (but well reproducible) positioning of the studied molecule is then carried out. Here we present the test case of NH$_3$, an ubiquitous species in the molecular ISM. We provide the BE distribution computed by a hierarchy approach, using the semiempirical xTB-GFN2 as low-level method to describe the whole icy cluster combined with the B97D3 DFT functional as high-level method on the local zone of the NH$_3$ interaction. The final ZPE corrected BE is computed at ONIOM(DLPNO-CCSD(T)//B97D3:xTB-GFN2) level, ensuring the best cost/accuracy ratio. The main peak of the predicted NH$_3$ BE distribution is in agreement with experimental TPD and literature computed data. A second broad peak at very low BE values is also present, never detected before. It may provide the solution to a long-standing puzzle about the presence of gaseous NH$_3$ observed also in cold ISM objects.

HCN in the gas form is considered as a primary nitrogen source for the synthesis of prebiotic molecules in extraterrestrial environments. Nevertheless, the research mainly focused on the reactivity of HCN and its derivatives in aqueous systems, often using external high-energy supply in the form of cosmic rays or high energy photons. Very few studies have been devoted to the chemistry of HCN in the gas phase or at the gas/solid interphase, although they represent the more common scenarios in the outer space. In this paper we report about the reactivity of highly pure HCN in the 150-300 K range at the surface of amorphous and crystalline Mg

Inhaled crystalline silica causes inflammatory lung diseases, but the mechanism for its unique activity compared to other oxides remains unclear, preventing the development of potential therapeutics. Here, the molecular recognition mechanism between membrane epitopes and "nearly free silanols" (NFS), a specific subgroup of surface silanols, is identified and proposed as a novel broad explanation for particle toxicity in general. Silica samples having different bulk and surface properties, specifically different amounts of NFS, are tested with a set of membrane systems of decreasing molecular complexity and different charge. The results demonstrate that NFS content is the primary determinant of membrane disruption causing red blood cell lysis and changes in lipid order in zwitterionic, but not in negatively charged liposomes. NFS-rich silica strongly and irreversibly adsorbs zwitterionic self-assembled phospholipid structures. This selective interaction is corroborated by density functional theory and supports the hypothesis that NFS recognize membrane epitopes that exhibit a positive quaternary amino and negative phosphate group. These new findings define a new paradigm for deciphering particle-biomembrane interactions that will support safer design of materials and what types of treatments might interrupt particle-biomembrane interactions.

The formation of the interstellar complex organic molecules (iCOMs) is a hot topic in astrochemistry. One of the main paradigms trying to reproduce the observations postulates that iCOMs are formed on the ice mantles covering the interstellar dust grains as a result of radical--radical coupling reactions. We investigate iCOMs formation on the icy surfaces by means of computational quantum mechanical methods. In particular, we study the coupling and direct hydrogen abstraction reactions involving the CH$_3$ + X systems (X = NH$_2$, CH$_3$, HCO, CH$_3$O, CH$_2$OH) and HCO + Y (Y = HCO, CH$_3$O, CH$_2$OH), plus the CH$_2$OH + CH$_2$OH and CH$_3$O + CH$_3$O systems. We computed the activation energy barriers of these reactions as well as the binding energies of all the studied radicals, by means of density functional theory (DFT) calculations on two ice water models, made of 33 and 18 water molecules. Then, we estimated the efficiency of each reaction using the reaction activation, desorption and diffusion energies and derived kinetics with the Eyring equations. We find that radical--radical chemistry on surfaces is not as straightforward as usually assumed. In some cases, direct H abstraction reactions can compete with radical--radical couplings, while in others they may contain large activation energies. Specifically, we found that (i) ethane, methylamine and ethylene glycol are the only possible products of the relevant radical--radical reactions; (ii) glyoxal, methyl formate, glycolaldehyde, formamide, dimethyl ether and ethanol formation is likely in competition with the respective H-abstraction products, and (iii) acetaldehyde and dimethyl peroxide do not seem a likely grain surface products., 46 pages, 15 figures. Accepted for publication in ApJs

Interstellar grains are composed by a rocky core (usually amorphous silicates) covered by an icy mantle, the most abundant molecule being H

The biological activity of proteins is partly due to their secondary structures and conformational states that may change in the presence of mineral surfaces.

Ethanol (CH$_3$CH$_2$OH) is a relatively common molecule, often found in star forming regions. Recent studies suggest that it could be a parent molecule of several so-called interstellar complex organic molecules (iCOMs). Yet, the formation route of this species remains debated. In the present work, we study the formation of ethanol through the reaction of CCH with one H$_2$O molecule belonging to the ice, as a test case to investigate the viability of chemical reactions based on a "radical + ice component" scheme as an alternative mechanism for the synthesis of iCOMs, beyond the usual radical-radical coupling. This has been done by means of DFT calculations adopting two clusters of 18 and 33 water molecules as ice models. Results indicate that CH$_3$CH$_2$OH can potentially be formed by this proposed reaction mechanism. The reaction of CCH with H$_2$O on the water ice clusters can be barrierless (thanks to the help of boundary icy water molecules acting as proton transfer assistants) leading to the formation of vinyl alcohol precursors (H$_2$CCOH and CHCHOH). Subsequent hydrogenation of vinyl alcohol yielding ethanol is the only step presenting a low activation energy barrier. We finally discuss the astrophysical implications of these findings., 30 pages, 6 figures Accepted for publication ACS Earth and Space Chemistry

Binding energies (BEs) are one of the most important parameters for astrochemical modeling determining, because they govern whether a species stays in the gas-phase or is frozen on the grain surfaces. It is currently known that, in the denser and colder regions of the interstellar medium, sulphur is severely depleted in the gas phase. It has been suggested that it may be locked into the grain icy mantles. However, which are the main sulphur carriers is still a matter of debate. This work aims at establishing accurate BEs of 17 sulphur-containing species on two validated water ice structural models, the proton-ordered crystalline (010) surface and an amorphous water ice surface. We adopted Density Functional Theory (DFT)-based methods (the hybrid B3LYP-D3(BJ) and the hybrid meta-GGA M06-2X functionals) to predict structures and energetics of the adsorption complexes. London's dispersion interactions are shown to be crucial for an accurate estimate of the BEs due to the presence of the high polarizable sulphur element. While on the crystalline model the adsorption is restricted to a very limited number of binding sites with single valued BEs, on the amorphous model several adsorption structures are predicted, giving a BE distribution for each species. With the exception of few cases, both experimental and other computational data are in agreement with our calculated BE values. A final discussion on how useful the computed BEs are with respect to the snow lines of the same species in protoplanetary disks is provided, Comment: 22 pages, 9 figures, Accepted for publication in The Astrophysical Journal

Computational modeling of protein/surface systems is challenging since the conformational variations of the protein and its interactions with the surface need to be considered at once. Adoption of first-principles methods to this purpose is overwhelming and computationally extremely expensive so that, in many cases, dramatically simplified systems (

Ethanol (CH

THE ''LIfe in Space'' project was funded in the wake of the Italian Space Agency's proposal for the development of a network of institutions and laboratories conceived to implement Italian participation in space astrobiology experiments. Of primary concern for this project is the study of the origin of life in the Universe, a focus that will promote investigation into prebiotic chemistry in various possible scenarios, whether in polar or nonpolar solvents (e.g., Titan's environment). Such results will link with study of the effects of simulated space conditions on possible chemical bio- signatures. The limits of life as we know it will be investigated in ground-based experiments with microorganisms that have already demonstrated their resistance to extreme environments on Earth and to real or simulated space conditions. The potential survival of microorganisms will also be examined with up-to-date molecular methods. The ability of some microorganisms to produce atmospheric and surface biosignatures when exposed to simulated conditions will be tested and compared with the possible existence of bio- signatures on potentially habitable exoplanets. Furthermore, the search for potentially habitable exoplanets, with space- based observational methods, will be optimized by way of dedicated climate models with the capacity to predict the detectability of atmospheric biosignatures for a broad range of planetary conditions. The project embraces the four most important topics in astrobiological research, as listed below, along with relevant contributions from the participating Italian institutions. Origins and evolution of organic compounds of biological significance in space (comets, asteroids, rocky planets, and moons); Prebiotic syntheses, origin of life, and early life; The limits of life and biological habitability: origin, evolution and adaptation of life in extreme environments on Earth and in space; Biomarkers for life detection in the Solar System and on exoplanets.

In this work, we characterize the surface sites of Mg2SiO4, a main constituent of dust grains from the interstellar medium/protoplanetary disks, by using infrared (IR) spectroscopy of adsorbed CO, ...

Collagen is a protein family defined by a triple helix motif, which comprises roughly one-third of the total human protein content. Decoding the reasons underlying the stability of the collagen triple helix is of both fundamental and applicative relevance, for instance, to guide collagen protein engineering. In principle, full quantum mechanical approaches based on density functional theory (DFT) are ideal to study the subtle physicochemical features of collagen. Unfortunately, the huge size of the protein prevents the straightforward application of DFT to realistic collagen protein models. In this paper, we propose a new realistic model of the collagen protein based on a periodic approach. The protein model exploits the intrinsic symmetry of the collagen triple helix, dramatically lowering the cost of the simulations. This allows using accurate hybrid DFT simulations (B3LYP-D/TZP) for systematic studies of the collagen protein features. We have tested the proposed model/level-of-theory combination to analyze the well-known proline-conformation/collagen-stability relationship. For this purpose, we have performed an extensive conformational analysis of the proline ring within the protein, clarifying some of the reasons linking specific ring conformations to helix positions. Throughout our data analysis, we have also obtained "for free" the collagen interstrand binding energy. Simulation results demonstrate that London dispersion interactions play a dominant role in the whole helix stability. The good agreement with the experimental data validates the use of the proposed model/level of theory to assist the active field of collagen-like peptide synthesis.

In this paper, we have studied the vibrational spectral features for the collagen triple helix using a dispersion corrected hybrid density functional theory (DFT-D) approach. The protein is simulated by an infinite extended polymer both in the gas phase and in a water micro-solvated environment. We have adopted proline-rich collagen models in line with the high content of proline in natural collagens. Our scaled harmonic vibrational spectra are in very good agreement with the experiments and allow for the peak assignment of the collagen amide I and III bands, supporting or questioning the experimental interpretation by means of vibrational normal modes analysis. Furthermore, we demonstrated that IR spectroscopy in the THz region can detect the small variations inherent to the triple helix helicity (10/3 over 7/2), thus elucidating the packing state of the collagen. So far, identifying the collagen helicity is only possible by means of crystal x-ray diffraction.

Positive ions play a fundamental role in the interstellar chemistry, especially in cold environments where chemistry is believed to be mainly ion-driven. However, in contrast with neutral species, most of the cations present in the astrochemical reaction networks are not fully characterized in the astrochemical literature. To fill up this gap, we have carried out new accurate quantum chemical calculations to identify the structures and energies of 262 cations with up to 14 atoms that are postulated to have a role in the interstellar chemistry. Optimised structures and rotational constants were obtained at M06-2X/cc-pVTZ level, while electric dipoles and total electronic energies were computed with CCSD(T)/aug-cc-pVTZ//M06-2X/cc-pVTZ single point energy calculations. The present work complements the study by Woon & Herbst (2009), who characterised the structure and energies of 200 neutral species involved as well in the interstellar chemistry. Taken together, the two datasets can be used to estimate whether a reaction, postulated in present astrochemical reaction networks, is feasible from a thermochemistry point of view and, consequently, to improve the reliability of the present networks used to simulate the interstellar chemistry. We provide an actual example of the potential use of the cations plus neutral datasets. It shows that two reactions, involving Si-bearing ions and present in the widely used reaction networks KIDA and UMIST, cannot occur in cold ISM because endothermic.

Interstellar grains are known to be important actors in the formation of interstellar molecules such as H$_2$, water, ammonia, and methanol. It has been suggested that the so-called interstellar complex organic molecules (iCOMs) are also formed on the interstellar grain icy surfaces by the combination of radicals via reactions assumed to have an efficiency equal to unity. In this work, we aim to investigate the robustness or weakness of this assumption by considering the case of acetaldehyde (CH$_3$CHO) as a starting study case. In the literature, it has been postulated that acetaldehyde is formed on the icy surfaces via the combination of HCO and CH$_3$. Here we report new theoretical computations on the efficiency of its formation. To this end, we coupled quantum chemical calculations of the energetics and kinetics of the reaction CH$_3$ + HCO, which can lead to the formation of CH$_3$CHO or CO + CH$_4$. Specifically, we combined reaction kinetics computed with the Rice-Ramsperger-Kassel-Marcus (RRKM) theory (tunneling included) method with diffusion and desorption competitive channels. We provide the results of our computations in the format used by astrochemical models to facilitate their exploitation. Our new computations indicate that the efficiency of acetaldehyde formation on the icy surfaces is a complex function of the temperature and, more importantly, of the assumed diffusion over binding energy ratio $f$ of the CH$_3$ radical. If the ratio $f$ is $\geq$0.4, the efficiency is equal to unity in the range where the reaction can occur, namely between 12 and 30 K. However, if $f$ is smaller, the efficiency dramatically crashes: with $f$=0.3, it is at most 0.01. In addition, the formation of acetaldehyde is always in competition with that of CO + CH$_4$., Comment: 14 pages, 12 figures, 11 tables, accepted in A&A

Computational modeling of protein/surface systems is challenging since the conformational variations of the protein and its interactions with the surface need to be considered at once. Adoption of first-principles methods to this purpose is overwhelming and computationally extremely expensive so that, in many cases, dramatically simplified systems (e.g., small peptides or amino acids) are used at the expenses of modeling nonrealistic systems. In this work, we propose a cost-effective strategy for the modeling of peptide/surface interactions at a full quantum mechanical level, taking the adsorption of polyglycine on the TiO2 (101) anatase surface as a test case. Our approach is based on applying the periodic boundary conditions for both the surface model and the polyglycine peptide, giving rise to full periodic polyglycine/TiO2 surface systems. By proceeding this way, the considered complexes are modeled with a drastically reduced number of atoms compared with the finite-analogous systems, modeling the polypeptide structures at the same time in a realistic way. Within our modeling approach, full periodic density functional theory calculations (including implicit solvation effects) and ab initio molecular dynamics (AIMD) simulations at the PBE-D2* theory level have been carried out to investigate the adsorption and relative stability of the different polyglycine structures (i.e., extended primary, β-sheet, and α-helix) on the TiO2 surface. It has been found that, upon adsorption, secondary structures become partially denatured because the peptide C═O groups form Ti-O═C dative bonds. AIMD simulations have been fundamental to identify these phenomena because thermal and entropic effects are of paramount importance. Irrespective of the simulated environments (gas phase and implicit solvent), adsorption of the α-helix is more favorable than that of the β-sheet because in the former, more Ti-O═C bonds are formed and the adsorbed secondary structure results less distorted with respect to the isolated state. Under the implicit water solvent, additionally, adsorbed β-sheet structures weaken with respect to their isolated states as the H-bonds between the strands are longer due to solvation effects. Accordingly, the results indicate that the preferred conformation upon adsorption is the α-helix over the β-sheet.

There are different environments in the interstellar medium (ISM), depending on the density, temperature and chemical composition. Among them, molecular clouds, often referred to as the cradle of stars, are paradigmatic environments relative to the chemical diversity and complexity in space. Indeed, there, radio to far-infrared observations revealed the presence of several molecules in the gas phase, while near-infrared spectroscopy detected the existence of submicron sized dust grains covered by H2O -dominated ice mantles. The interaction between gas-phase species and the surfaces of water ices is measured by the binding energy (BE), a crucial parameter in astrochemical modelling. In this work, the BEs of a set of sulphur-containing species on water ice mantles have been computed by adopting a periodic ab initio approach using a crystalline surface model. The Density Functional Theory (DFT)-based B3LYP-D3(BJ) functional was used for the prediction of the structures and energetics. DFT BEs were refined by adopting an ONIOM-like procedure to estimate them at CCSD(T) level toward complete basis set extrapolation, in which a very good correlation between values has been found. Moreover, we show that geometry optimization with the computationally cheaper HF-3c method followed by single point energy calculations at DFT to compute the BEs is a suitable cost-effective recipe to arrive at BE values of the same quality as those computed at full DFT level. Finally, computed data were compared with the available literature data., Proceedings of the 21st International Conference on Computational Science and Its Applications, ICCSA 2021

Molecular hydrogen is the most abundant molecular species in the Universe. While no doubts exist that it is mainly formed on the interstellar dust grain surfaces, many details of this process remain poorly known. In this work, we focus on the fate of the energy released by the H$_2$ formation on the dust icy mantles, how it is partitioned between the substrate and the newly formed H$_2$, a process that has a profound impact on the interstellar medium. We carried out state-of-art \textit{ab-initio} molecular dynamics simulations of H$_2$ formation on periodic crystalline and amorphous ice surface models. Our calculations show that up to two thirds of the energy liberated in the reaction ($\sim$300 kJ/mol $\sim$3.1 eV) is absorbed by the ice in less than 1 ps. The remaining energy ($\sim$140 kJ/mol $\sim$1.5 eV) is kept by the newly born H$_2$. Since it is ten times larger than the H$_2$ binding energy on the ice, the new H$_2$ molecule will eventually be released into the gas-phase. The ice water molecules within $\sim$4 \AA ~from the reaction site acquire enough energy, between 3 and 14 kJ/mol (360--1560 K), to potentially liberate other frozen H$_2$ and, perhaps, frozen CO molecules. If confirmed, the latter process would solve the long standing conundrum of the presence of gaseous CO in molecular clouds. Finally, the vibrational state of the newly formed H$_2$ drops from highly excited states ($\nu = 6$) to low ($\nu \leq 2$) vibrational levels in a timescale of the order of ps., Comment: 13 pages, 7 figures Submitted to ApJ (in press)

Forsterite is a nesosilicate with Mg2SiO4 composition, representing the iron-free endmember of the family of olivines. Interestingly, aside its finding as mineral component of the Earth’s crust and mantle, it has been observed in extraterrestrial environments where have been found as principal inorganic constituents of meteorites, comets and in the core of dust grains found in the interstellar medium and in protoplanetary disks [1]. It has often been indicated that these grains could be possible sites for the occurrence of astrochemical reactions involving simple prebiotic molecules (SPM, e.g. CO, CO2, H2O, HCN, etc.). In order to assess the role of Mg2SiO4 in this prebiotic scenario, the understanding of the surface properties of grain-core phases is of primary importance. We thoroughly characterized two Mg2SiO4 model samples, namely an amorphous magnesium silicate (AMS) and a crystalline forsterite (Forst), and we compared their surface acid-base properties as a function of their structure (amorphous vs crystalline) [2]. The AMS sample was synthesized via thermal plasma route, as proposed by Koike et al. [3], whereas Forst was obtained by thermal annealing of the former at 1073 K. The acid-base properties of the two systems were investigated by monitoring the adsorption of selected probe molecules (CO, CO2 and CD3CN) by IR spectroscopy and then by studying the perturbation of their vibrational fingerprints upon interaction with specific surface functionalities. As an example, the IR spectra of CD3CN adsorbed on AMS and Forst in the υ(CN) frequency range are shown in Figure 1. The spectra for both materials are characterized by three main bands at 2300, 2266 and 2215 cm-1. The 2300 cm-1 component is assigned to CD3CN interacting with Lewis acid sites, i.e. surface Mg2+ cations, whereas the 2266 cm-1 band is assigned to the features of CD3CN interacting with weak Bronsted acid sites (surface silanols) and of not interacting CD3CN forming multilayers. These components are closely similar among both samples. Instead, they remarkably differ with respect to the 2215 cm-1 band, which is much more intense in AMS than in Forst. We assigned this signal to anionic species formed by deprotonation of acetonitrile in presence of strong surface basic sites. These results, confirmed also by the adsorption of other probe molecules, showed as AMS and Forst have a similar population of surface acid sites, whereas only the former shows a significant surface basicity. Finally, we investigated HCN adsorption on both samples. HCN is a molecule of particular interest since its adsorption and reactivity on silicates in interstellar media is supposed to play a role in the synthesis of biomolecules contributing to the development of life [4]. The HCN reaction leads to the formation of a variety of oligomers (at least up to 12 terms) and the surface basicity, already highlighted by the other probe molecules, seems to play a key role in the process. Figure 1. IR spectra of AMS and Forst outgassed for 2 hours at 673 K in vacuum and contacted with 40 mbar of CD3CN at r.t. (curves a) and outgassed for 30 min at r.t. after CD3CN contact (curves b). Spectra collected at decreasing CD3CN pressures are reported as thin lines for both materials. The contribution from the bare activated material has been subtracted. The spectra have been normalized to the specific surface area of the samples. References [1] T. Henning, Cosmic Silicates. Annu. Rev. Astron. Astrophys. 2010, 48, 21–46. [2] M. Signorile, L. Zamirri, A. Tsuchiyama, P. Ugliengo, F. Bonino, G. Martra, ACS Earth Sp. Chem. 2020, 4, 345–354. [3] C. Koike, Y. Imai, H. Chihara, H. Suto, K. Murata, A. Tsuchiyama, S. Tachibana, S. Ohara, Astrophys. J. 2010, 709, 983–992 [4] J. P. Ferris, and W. J. Hagan Jr, Tetrahedron. 1984, 40, 1093-1120.

Formamide is abundant in the interstellar medium and was also present during the formation of the Solar system through the accretion process of interstellar dust. Under the physicochemical conditions of primordial Earth, formamide could have undergone decomposition, either via dehydration (HCN + H2O) or via decarbonylation (CO + NH3). The first reactive channel provides HCN, which is an essential molecular building block for the formation of RNA/DNA bases, crucial for the emergence of life on Earth. In this work, we studied, at the CCSD(T)/cc-pVTZ level, the two competitive routes of formamide decomposition, i.e. dehydration and decarbonylation, either in liquid formamide (by using the polarization continuum model technique) or at the interface between liquid formamide and amorphous silica. Amorphous silica was adopted as a convenient model of the crystalline silica phases ubiquitously present in the primordial (and actual) Earth's crust, and also due to its relevance in catalysis, adsorption and chromatography. Results show that: (i) silica surface sites catalyse both decomposition channels by reducing the activation barriers by about 100 kJ mol−1 with respect to the reactions in homogeneous medium, and (ii) the dehydration channel, giving rise to HCN, is strongly favoured from a kinetic standpoint over decarbonylation, the latter being, instead, slightly favoured from a thermodynamic point of view.

The mechanism of the peptide-bond formation between two glycine (Gly) molecules has been investigated by means of PBE-D2* and PBE0-D2* periodic simulations on the TiO2 (101) anatase surface. This is a process of great relevance both in fundamental prebiotic chemistry, as the reaction univocally belongs to one of the different organizational events that ultimately led to the emergence of life on Earth, as well as from an industrial perspective, since formation of amides is a key reaction for pharmaceutical companies. The efficiency of the surface catalytic sites is demonstrated by comparing the reactions in the gas phase and on the surface. At variance with the uncatalyzed gas-phase reaction, which involves a concerted nucleophilic attack and dehydration step, on the surface these two steps occur along a stepwise mechanism. The presence of surface Lewis and Bronsted sites exerts some catalytic effect by lowering the free energy barrier for the peptide-bond formation by about 6 kcal mol-1 compared to the gas-phase reaction. Moreover, the co-presence of molecules acting as proton-transfer assistants (i.e., H2 O and Gly) provide a more significant kinetic energy barrier decrease. The reaction on the surface is also favorable from a thermodynamic standpoint, involving very large and negative reaction energies. This is due to the fact that the anatase surface also acts as a dehydration agent during the condensation reaction, since the outermost coordinatively unsaturated Ti atoms strongly anchor the released water molecules. Our theoretical results provide a comprehensive atomistic interpretation of the experimental results of Martra et al. (Angew. Chem. Int. Ed. 2014, 53, 4671), in which polyglycine formation was obtained by successive feedings of Gly vapor on TiO2 surfaces in dry conditions and are, therefore, relevant in a prebiotic context envisaging dry and wet cycles occurring, at mineral surfaces, in a small pool.

The mechanism of the amide bond formation between nonactivated carboxylic acids and amines catalyzed by the surface of amorphous silica under dry conditions is elucidated by combining spectroscopic measurements and quantum chemical simulations. The results suggest a plausible explanation of the catalytic role of silica in the reaction. Both experiment and theory identify very weakly interacting SiOH surface group pairs (ca. 5 A apart) as key specific sites for simultaneously hosting, in the proper orientation, ionic and canonical pairs of the reactants. An atomistic interpretation of the experiments indicates that this coexistence is crucial for the occurrence of the reaction, since the components of the canonical pair are those undergoing the amidation reaction while the ionic pair directly participates in the final dehydration step. Transition state theory based on quantum mechanical free energy potential energy shows the silica-catalyzed amide formation as being relatively fast. The work also points ou...

Bone has a hierarchical structure based on the mineralized fibril, an organic matrix envisaging collagen protein in tight interaction with hydroxyapatite mineral (HAP) and stabilized by water molecules. The tremendous complexity of this natural composite material hides the extraordinary features in terms of high compressive strength and elasticity imparted by the collagen protein. Clearly, understanding the nanoscale interface and mechanics of bone at atomistic level can dramatically improve the development of biocomposite and the understanding of bone related diseases. In this work, we aim at elucidating the features of the interaction between a model of a single-collagen-strand (COL) with the most common dried P-rich (010) HAP surface. The methods of choice are static and dynamic simulations based on density functional theory at PBE-D2, PBE-D3 and B3LYP-D3 levels. Collagen is made to a large extent by proline (PRO) and derivatives, and PRO’s side chain is known to affect the collagen triple helix stabil...

Aromatase catalyses the biosynthesis of estrogens from androgens. Due to the physiological importance of this conversion of lipophilic substrates, the interaction with the lipid bilayer for this cytochrome P450 is crucial for its dynamics that must allow an easy access to substrates and inhibitors. Here, aromatase-anastrozole interaction is studied combining computational methods to identify possible access/egress routes with the protein inserted in the membrane and experimental tools aimed at the investigation of the effect of the inhibitor on the protein conformation. By means of MD simulations of the protein inserted in the membrane, two channels, not detected in the starting crystal structure, are found after a 20 ns simulation. Trypsin digestion on the recombinant protein shows that the enzyme is strongly protected by the presence of the substrate and even more by the inhibitor. DSC experiments show an increase in the melting temperature of the protein in complex with the substrate (49.3°C) and the inhibitor (58.7°C) compared to the ligand-free enzyme (45.9°C), consistent with a decrease of flexibility of the protein. The inhibitor anastrozole enters the active site of the protein through a channel different from that used from the substrate and promotes a conformational change that stiffen the protein conformation and decrease protein-protein interaction between different aromatase molecules. This article is protected by copyright. All rights reserved

Formation of interstellar complex organic molecules is currently thought to be dominated by the barrierless coupling between radicals on the interstellar icy grain surfaces. Previous standard DFT results on the reactivity between CH$_3$ and HCO on amorphous water surfaces, showed that formation of CH$_4$ + CO by H transfer from HCO to CH$_3$ assisted by water molecules of the ice was the dominant channel. However, the adopted description of the electronic structure of the biradical (i.e., CH$_3$/HCO) system was inadequate (without the broken-symmetry (BS) approach). In this work, we revisit the original results by means of BS-DFT both in gas phase and with one water molecule simulating the role of the ice. Results indicate that adoption of BS-DFT is mandatory to describe properly biradical systems. In the presence of the single water molecule, the water-assisted H transfer exhibits a high energy barrier. In contrast, CH$_3$CHO formation is found to be barrierless. However, direct H transfer from HCO to CH$_3$ to give CO and CH$_4$ presents a very low energy barrier, hence being a potential competitive channel to the radical coupling and indicating, moreover, that the physical insights ofthe original work remain valid., Comment: Submitted to MNRAS main journal. For associated supporting material refer to the publication in MNRAS. Accepted 2020 February 14. Received 2020 February 14

In this work, we have computed the exfoliation energy (the energy required to separate a single layer from the bulk structure), the interlayer distance, and the thermodynamic state functions for representative layered inorganic minerals such as Brucite, Portlandite, and Kaolinite, while leaving the more classical 2D transition-metal dichalcogenides (like MoS2) for future work. Such materials are interesting for several applications in the field of adsorption and in prebiotic chemistry. Their peculiar features are directly controlled by the exfoliation energy. In materials without cations/anions linking different layers, the interactions keeping the layers together are of weak nature, mainly dispersion London interactions and hydrogen bonds, somehow challenging to deal with computationally. We used Hartree-Fock (HF) and density functional theory (DFT) approaches focusing on the role of dispersion forces using the popular and widespread Grimme's pairwise dispersion schemes (-D2 and -D3) and, as a reference method, the periodic MP2 approach based on localized orbitals (LMP2). The results are highly dependent on the choice of the scheme adopted to account for dispersion interactions. D2 and D3 schemes combined with either HF or DFT lead to overestimated exfoliation energies (about 2.5 and 1.7 times higher than LMP2 data for Brucite/Portlandite and Kaolinite) and underestimated interlayer distances (by about 3.5% for Brucite/Portlandite). The reason is that D2 and D3 corrections are based on neutral atomic parameters for each chemical element which, instead, behave as cations in the considered layered material (Mg, Ca, and Al), causing overattractive interaction between layers. More sophisticated dispersion corrections methods, like those based on nonlocal vdW functionals, many body dispersion model, and exchange-hole dipole moment not relying on atom-typing, are, in principle, better suited to describe the London interaction of ionic species. Nonetheless, we demonstrate that good results can be achieved also within the simpler D2 and D3 schemes, in agreement with previous literature suggestions, by adopting the dispersion coefficients of the preceding noble gas for the ionic species, leading to energetics in good agreement with LMP2 and structures closer to the experiments.