European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Bystrov V., Paramonova E., Bystrova N., Sapronova A., Filippov S. Institute of Mathematical Problems of Biology RAS, Pushchino, , Moscow region, Russia Hydroxyapatite

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Bystrov V., Paramonova E., Bystrova N., Sapronova A., Filippov S. Institute of Mathematical Problems of Biology RAS, Pushchino, , Moscow region, Russia

PERCERAMICS Project NMP3-CT of FP6 ( EC ) on years. Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatite The project will develop a percolated nanostructured electrically polarized ceramics (CER) fabricated from hydroxylapatite (HAP) to improve quality of bone eligible bioimplants, work out new material for immobilization of microorganisms for their further use to product of various biologically active compounds (BAC) and purify the environment. A surface of CER will provide a relevant biological – non-biological interface to adhere cells/microorganisms. A surface morphology of CER will be supplied at a nano scale eligible for a cell receptor “tail” size and will be “packed” from HAP nanoparticles. The CER surface will be charged and supplied with a web of the canals. Engineering support employing knowledge acquired from computational physics research on charging and adhesion/cohesion by HAP nanoparticles will be provided. To meet CER applications the project is focused to: investigation of yeast cell physiology in biofilms immobilised in novel matrices; immobilization of bacterial cells and yeasts for the purification of the environment, bioremediation and industrial biotechnological processes; working out of active dry preparations of immobilized microorganisms; fabrication of bone eligible implants. The results are planned to implement in industry, medicine, environment and biotechnologies. New benefits in safety of environment, health and biotechnologies will be challenged. Professionals from computational and material physics, chemistry, engineering of materials and their characterization, microbiology, biotechnology, wastewater treatment, orthopaedics and industries will be involved on a multidisciplinary approach and a critical mass of the project. A sustainable development at relevant industries and research will spurt. The project partners’ cooperation will become stronger and reach European networking scale to strengthen and integrate the European Research Area.х

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Hydroxyapatite [Ca 5 (PO 4 ) 3 OH; (HAP)] corresponds to structure of mineral bone’s component leads to the new bone formation generated by osteoblasts on its surface if charged and polarized has specific surface characteristics improves adhesion properties provide additional stimulation of the interaction with living cells Processes of a charge transfer in the HAP structure cause the arising of the polarization and have electrets-like character Mechanism of polarization and surface electrical / mechanical (adhesion) properties changes are not clear

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Purpose: Investigation of the HAP structural changes and analyse mechanisms of charge transfer using the computer simulation of HAP crystal nanostructures Software: Voxel; HyperChem; Crystals; Babel; Gaussian-98

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Used experimental data on HAP structure from ftp://ftp.geo.arizona.edu/pub/xtal/data/AMCfiles/01209.amcftp://ftp.geo.arizona.edu/pub/xtal/data/AMCfiles/01209.amc In the program Crystals are received the *.pdb file with coordinates of all atoms (for one and several channels) and qualitative images of HAP structure.

Parameters of the elementary crystal cell unit: a = b = 9,4166 Angstrem = 0,94166 nm, c = 6,8745 Angstrem = 0,68745 nm. European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite xyz нм Ca10,62780,31390,0010 Ca2-0,00620,23260,1719 P0,34710,37540,1719 O10,45670,30970,1719 O20,43780,55280,1719 O30,24290,32350,0483 O(H)000,1360 H000,0275

abc 9,4166 6,8745 x yz Å atom Ca16,27773,13890,0099 Ca2-0,06192,32651,7186 P3,47103,75401,7186 O14,56713,09711,7186 O24,37785,52851,7186 O32,42953,23460,4833 O(H)001,3605 H000,2750 Parameters of cell unit:

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite HAP structure channels (parallel with c axes )

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite H + ion rotation model H+ ion transportation polarization / depolarization are attributed to rotation of a proton around OH - in the colon-like channels proton turns around O 2 2- ion, then moves to the next vacancy O - proton transfer on the large distances in the channels

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Proton transfer as possible mechanism of HAP polarization Mathematical description of the system 1. Model of a discrete medium m - proton mass, u n - proton displacement (1) Varying (1) yields the Euler–Lagrange equations of motion (2)  1 - damping in the system, F = qE - external field (q – charge, E - electric field),

Quantum-chemical calculations of proton transport between two methylamine molecules with and without external electric field, carried out with the GAUSSIAN-98 code (as example) European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Change of spacing Change of electric field

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite 2.Continuous medium model (N   and l 0 = c 0 /  0  0 N   and l 0 = c 0 /  0  0 (3) Potential energy (4) (5) equation of motion

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite proton subsystem ion subsystem

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Sofware for computational visualization and animation of Hydroxyapatite structure 1.The CRYSTALS software package for single crystal X-ray structure refinement and analysis consists of CRYSTALS, Cameron and specially recompiled versions of SIR92 and SHELXS. 2. The CINEMA 4D XL Bundle includes advanced tools for professional users, including character animation utilities and advanced rendering and particle features. To visualize molecular structures we have used a plug-in for Cinema 4D developed in the Institute of Mathematical Problems of Biology RAS.

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite Cinema 4D equipped with the plug-in can build molecular models from PDB-files and has enabled us to employ in the visualization the following technologies of professional computer 3D-graphics: 1.. Use of character animation (forward and inverse kinematics) for modeling conformational changes. 2.. Use of expressions for modeling the behavior of molecular groups. 3.. Use of particle systems for special effects to visualize objects without clearly defined shape.

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computation of Molecular Nanostructure and Mechanical Properties of Hydroxyapatite P 6/m Explored initial HAP structure (group of symmetry are: P6/m and P6 3 /m.)

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite P 6 3 /m Са OH P O

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite P 6 3 /m Са only OH Ca P O

Fig.4.(a, b). Tree-dimensional HAP structures (one channel), P 6/m symmetry P 6/m

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite

European Commission PROJECT NMP3-CT “Multifunctional percolated nanostructured ceramics fabricated from hydroxylapatyte” Computational Molecular Nanostructures and Mechanical Properties of Hydroxyapatite As results were obtained detailed computational structural models (quantum-chemical, soliton and continual) and calculated parameters of HAP nanoparticles for different symmetry groups. These results were obtained by using and adaptation of HyperChem, Crystals, Gaussian-98 and several special elaborated software of Dr. Bystrov group from IMPB. The calculated structural HAP properties and peculiarities allow us to understand (to clarify) the mechanism of charge (proton) transport (transfer) and surface charging of HAP nanoparticles. The estimated values of surface charge is ~ 0.1 C/m 2 which is corresponded to known experimental data. CONCLUSION