Marta Corno

Ab Initio Modeling of Protein/Biomaterial Interactions : Glycine Adsorption at Hydroxyapatite Surfaces

How does glycine adsorb at hydroxyapatite surfaces? Ab initio simulations based on periodic B3LYP GTO calculations reveal the detailed mechanism of binding to the (001) and (010) surfaces by shedding light on how acid and basic amino acid residues of proteins interact with hydroxyapatite based biomaterials.

The vibrational features of hydroxylapatite and type A carbonated apatite: A first principle contribution

Abstract In this work, the vibrational spectra of hexagonal hydroxylapatite OHAp (space group P63) and type A carbonated apatite [Ca10(PO4)6(CO3), space group P1] have been calculated with an ab initio approach by the density function method using the hybrid B3LYP functional and an all-electron polarized double-ζ quality Gaussian-type basis set using the CRYSTAL09 computer program. The effect on the vibrational properties due to improving the Ca pseudopotential, usually adopted in previous studies on hydroxylapatite, toward the present all-electron basis set has also been briefly addressed. The anharmonic correction for hydroxyl groups in OHAp has also been considered. The results of the modeling are in good agreement with the available FTIR and Raman data presented in the literature and can be useful to experimental researchers to assign unequivocally the bands in infrared and Raman spectra to specific fundamental vibrational modes.

Coordination chemistry of Ca sites at the surface of nanosized hydroxyapatite: interaction with H2O and CO

The affinity towards water of a selection of well-defined, nanostructured hydroxyapatite (HA) samples was investigated by H2O vapour adsorption microcalorimetry and infrared (IR) spectroscopy. A large hydrophilicity of all investigated materials was confirmed. The surface features of hydrated HA were investigated on the as-synthesized samples pre-treated in mild conditions at T=303 K, whereas dehydrated HA features were characterized on samples activated at T=573 K. The relatively large hydrophilicity of the hydrated surface (−ΔadsH∼100–50 kJ mol−1) was due to the interaction of water with the highly polarized H2O molecules strongly coordinated to the surface Ca2+ cations. At the dehydrated surface, exposing coordinatively unsaturated (cus) Ca2+ cations, H2O was still molecularly adsorbed but more strongly (−ΔadsH∼120–90 kJ mol−1). The use of CO adsorption to quantify the Lewis acidic strength of HA surface sites revealed only a moderate strength of cus Ca2+ cations, as confirmed by both microcalorimetric and IR spectroscopic measurements and ab initio calculations. This result implies that the large HA/H2O interaction energy is due to the interplay between cus Ca2+ sites and nearby hydrophilic PO4 groups, not revealed by the CO probe. The lower density of cus Ca2+ cations at the 573 K activated HA surface with respect to the pristine one did not affect the whole hydrophilicity of the surface, as the polarizing effect of Ca sites is so strong to extend up to the fourth hydrated layer, as confirmed by both high-coverage microcalorimetric and IR spectroscopic data. No specific effects due to the investigated specimen preparation method and/or different morphology were observed.

Ab initio modeling of protein/biomaterial interactions: competitive adsorption between glycine and water onto hydroxyapatite surfaces

Both glycine and water exhibit a high affinity towards the hydroxyapatite HA surfaces. What happens when they are co-adsorbed at the HA (001) surface? B3LYP periodic calculations reveal that glycine displaces the pre-adsorbed water interacting directly with the HA surface.

Silica-Based Materials as Drug Adsorbents: First Principle Investigation on the Role of Water Microsolvation on Ibuprofen Adsorption

Silica-based materials find applications as excipients and, particularly for those of mesoporous nature, as drug delivery agents for pharmaceutical formulations. Their performance can be crucially affected by water moisture, as it can modify the behavior of these formulations, by limiting their shelf life. Here we describe the role of water microsolvation on the features of ibuprofen adsorbed on a model of amorphous silica surface by means of density functional theory (DFT) simulations. Starting from the results of the simulation of ibuprofen in interaction with a dry hydrophobic amorphous silica surface, a limited number of water molecules has been added to study the configurational landscape of the microsolvated system. Structural and energetics properties, as well as the role of dispersive forces, have been investigated. Our simulations have revealed that the silica surface exhibits a higher affinity for water than for ibuprofen, even if several structures coexist at room temperature, with an active competition of ibuprofen and water for the exposed surface silanols. Dispersive interactions play a key role in this system, as pure DFT fails to correctly describe its potential energy surface. Indeed, van der Waals forces are the leading contribution to adsorption, independently of whether the drug is hydrogen-bonded directly to the surface or via water molecules.

Periodic B3LYP study of hydroxyapatite (001) surface modelled by thin layer slabs

The (001) surface of the hexagonal hydroxyapatite HA [Ca 10 (PO 4 ) 6 (OH) 2 , layer group P 3] is simulated with the slab approach by fully optimizing (cell size and internal coordinates) two models, respectively 6 A and 14 A thick, in a fully ab initio periodic approach. The B3LYP hybrid functional and a Gaussian basis set of polarized double zeta quality and pseudo potentials for Ca ions only have been adopted, as encoded in the CRYSTAL03 computer program. Both slab models are cut out of the optimized structure of the hexagonal HA bulk phase ( P 6 3 space group). Because the (001) surface derived from the hexagonal HA shows ferroelectricity due to the orientation of the OH groups, the convergence of the E surf with the slab thickness (until a thickness of about 60 A) has been studied at B3LYP level on slabs whose geometry has been optimized using the GULP program with a recently developed shell-ion model potential. Structural and electronic features are addressed and a comparison between results for the considered slabs is carried out with respect to the: i) surface energy, E surf ; ii) geometrical relaxation; iii) band gap, field across the slab and Mulliken analysis; iv) electrostatic features in close proximity of the surface; v) harmonic/anharmonic OH vibrational features. The same procedure has been adopted for non-ferroelectric slabs derived from the HA monoclinic phase (bulk belonging to the P 2 1 / b space group). E surf for hexagonal HA increases slightly, as a function of the slab thickness, from 1.080 J/m 2 (doublelayer) to 1.107 J/m 2 (nonalayer), showing that the OH ferroelectricity imparts an instability of ≈0.003 J/m 2 for each added layer (7 A thick). For the non-ferroelectric HA monoclinic phase, E surf converges to 1.337 J/m 2 within 1.0 −4 J/m 2 already for the doublelayer. It is shown that the OH ferroelectricity does not prevent the formation of a (001) slab of thickness of at least 10 nm, a fact relevant for technological applications. The HA doublelayer slab is suggested as a proper model of the HA (001) face to study adsorption processes relevant to understand the role of hydroxyapatite surface in biological processes.

Periodic ab initio bulk investigation of hydroxylapatite and type A carbonated apatite with both pseudopotential and all-electron basis sets for calcium atoms

Abstract Apatite minerals draw the attention of many researchers not only in mineralogy, but also in biology, biochemistry, and medicine because hydroxylapatite [Ca10(PO4)6(OH)2] is the main component of the mineral phase of mammalian bones. However, in nature this mineral is mostly present with various stoichiometric defects. The carbonate ion is found commonly in its structure where it can occupy different crystallographic sites; however, its configurational energy and relative orientation in the apatite lattice is still debated. In this work, bulk structural features of hexagonal hydroxylapatite (space group P63) and type A carbonated apatite [Ca10(PO4)6(CO3), space group P1] have been modeled by density function method using the hybrid B3LYP functional and an all-electron polarized double-ζ quality Gaussian-type basis set using the CRYSTAL09 computer program. The effect on the structural parameters due to the adoption of the present all-electron basis set for the Ca ion compared to the pseuodpotential adopted in previous work has also been discussed. Different orientations of the carbonate ion in the apatite unit cell have been considered. The B3LYP functional and Gaussian-type basis set with polarization have been adopted. The geometry of the model (lattice parameters and internal coordinates) has been fully optimized and resulted in very good agreement with XRD data reported in literature that suggest a “close” configuration (type A1) of the carbonate ion, i.e., with a C-O bond perpendicular to the c-axis of the apatite cell.

An ab initio parameterized interatomic force field for hydroxyapatite

A classical interatomic force field for hydroxyapatite has been parameterized from periodic ab initio calculations carried out on the hexagonal structure (space group P63). The GULP program has been used for fitting geometry and phonon frequencies computed with the CRYSTAL06 program using the B3LYP hybrid functional and Gaussian-type basis set of polarized double zeta quality. Polarization effects and covalent bonding have been included through the shell-ion model potential. Excellent agreement has been found in reproducing structural features, lattice dynamics, the OH stretching vibrations and relative phase stabilities between the monoclinic structure (space group P21/b) and the hexagonal one. Transferability from hydroxyapatite to other calcium phosphates has also been demonstrated.

Ab initio modelling of protein-biomaterial interactions: influence of amino acid polar side chains on adsorption at hydroxyapatite surfaces

The adsorption from the gas phase of five different amino acids (AAs), namely Gly, Ser, Lys, Gln and Glu, on three surface models of hexagonal hydroxyapatite (HA) has been studied at B3LYP level with Gaussian type basis set within a periodic approach. The AA adsorption was simulated on the (001) and (010) stoichiometric surfaces, the latter both in its pristine and water-reacted form. Low/high AA coverage has been studied by doubling the HA unit cell size. The AAs have been docked to the HA surfaces following the electrostatic complementarity between the electrostatic potentials of AA and the bare HA. Gly adsorbs as a zwitterion at the (001) surface, whereas at the (010) ones, the proton of the COOH group is transferred to the surface resulting in an HA+/Gly− ion pair. For the other AAs, the common COOH−CH−NH2 moiety behaves like in Gly, while the specific side-chain functionalities adsorb at the HA surfaces by maximizing electrostatic and H-bond interactions. The interactions between the side chains and the HA surface impart a higher stability compared with the Gly case, with Glu being the strongest adsorbate owing to its high Ca affinity and H-bond donor propensity. For AAs of large size, the adsorption is more favourable in conditions of low coverage as repulsion between adjacent AAs is avoided. For all considered AAs, the strongest interaction is always established on the (010) faces rather than on the (001) one, therefore suggesting an easier growth along the c-direction of HA crystals from AA solutions.

Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations

Confinement in mesoporous silica can greatly increase the solubility of pharmaceutical compounds. Propionic acid derivatives (a very popular class of drugs that include ibuprofen and ketoprofen) would greatly benefit from such technology, given their common apolar character. However, it is still debated whether, after confinement, these drugs are adsorbed on the pore walls as individual molecules or they keep the H-bonded dimeric structure that exists in their crystalline form. Their physical state inside the mesopores could have important consequences on the final performances of the drug delivery system. We employed accurate periodic density functional theory simulations, both static and dynamic, to investigate the issue. We simulated ibuprofen, as a model for all propionic acid derivatives, adsorbed both as a monomer and as a dimer inside a realistic model for the MCM-41 mesoporous silica. We found that adsorption is energetically favored in both cases, driven by both vdW and H-bond interactions. However, through ab initio molecular dynamics, we observed a continuous forming, breaking and reforming of these interactions. In the end, by comparing computed energetics, vibrational spectra and mobility, we were able to provide some important clues on the physical state of this class of drugs inside mesoporous silica, helping to define which drug family (monomer or dimer) is more probable after confinement.