Molecular modeling based on empirical force fields as a tool for the characterization of nanostructures Jonáš Tokarský Conference IT4Innovations,

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1 Molecular modeling based on empirical force fields as a tool for the characterization of nanostructures

2 Outline TiO 2 nanoparticles on SiO 2 substrate

3 Outline TiO 2 nanoparticles on SiO 2 substrate Zr tetrameric cations intercalated into vermiculite

4 Outline TiO 2 nanoparticles on SiO 2 substrate Zr tetrameric cations intercalated into vermiculite vermiculite filler in polyethylene blend

5 Outline TiO 2 nanoparticles on SiO 2 substrate Zr tetrameric cations intercalated into vermiculite vermiculite filler in polyethylene blend biodegradable polymers as a drug carriers

6 TiO 2 nanoparticles on SiO 2 substrate J. Tokarský, V. Matějka, L. Neuwirthová, J. Vontorová, K. Mamulová Kutláková, J. Kukutschová, P. Čapková: A low-cost photoactive composite quartz/tio 2. Chemical Engineering Journal 222 (2013)

7 TiO 2 nanoparticles on SiO 2 substrate

8 TiO 2 nanoparticles on SiO 2 substrate

9 TiO 2 nanoparticles on SiO 2 substrate Si-O-Si SiO rings Si-O

10 TiO 2 nanoparticles on SiO 2 substrate Si-O-Si SiO rings Si-O-Ti Si-O

11 TiO 2 nanoparticles on SiO 2 substrate The fact that covalent bonds are only formed (during the DFT computation) in the models exhibiting the highest adhesion energies and minimum distances between atoms (when treated by empirical force field) shows that these two approaches are in good agreement.

12 TiO 2 nanoparticles on SiO 2 substrate SiO 2 (100) SiO 2 (110) SiO 2 (111) TiO 2 (100) TiO 2 (001) TiO 2 (110)

13 TiO 2 nanoparticles on SiO 2 substrate d Ti O = Å, 1930 Å C.J. Howard, et al. Acta Crystallogr.B 47 (1991) d Si O = Å J.D.H. Donnay, Y. Le Page, Acta Crystallogr. A 34 (1978)

14 TiO 2 nanoparticles on SiO 2 substrate J. Tokarský, P. Čapková: Structure compatibility of TiO 2 and SiO 2 surfaces. Applied Surface Science 284 (2013)

15 TiO 2 nanoparticles on SiO 2 substrate adhesion energy - number of Ti/O atomic pairs

16 TiO 2 nanoparticles on SiO 2 substrate TiO 2 (001) TiO 2 (100) TiO 2 (103) TiO 2 (110) TiO 2 (112) SiO 2 (001) SiO 2 (100) SiO 2 (101) SiO 2 (110) SiO 2 (111)

17 TiO 2 nanoparticles on SiO 2 substrate adhesion energy

18 TiO 2 nanoparticles on SiO 2 substrate number of Ti/O atomic pairs

19 TiO 2 nanoparticles on SiO 2 substrate TiO 2 (001)/SiO 2 (001)

20 TiO 2 nanoparticles on SiO 2 substrate TiO 2 (001)/SiO 2 (001)

21 TiO 2 nanoparticles on SiO 2 substrate TiO 2 (112)/SiO 2 (101)

22 TiO 2 nanoparticles on SiO 2 substrate TiO 2 (112)/SiO 2 (111)

23 TiO 2 nanoparticles on SiO 2 substrate

24 TiO 2 nanoparticles on SiO 2 substrate overlapping planes treated by MATLAB

25 Zr tetrameric cations intercalated into vermiculite M. Valášková, J. Tokarský, M. Hundáková, J. Zdrálková, B. Smetana: Role of vermiculite and zirconium-vermiculite on the formation of zirconiumcordierite nanocomposites. Applied Clay Science (2013)

26 Zr tetrameric cations intercalated into vermiculite The Zr 4+ vermiculites were studied in their new role of the zircon precursor for the zircon cordierite nanocomposites. [Zr 4 (OH) 14 (H 2 O) 10 ] 2+ [Zr 4 (OH) 8 (H 2 O) 16 ] 8+ [Zr 4 (OH) 20 (H 2 O) 24 ] 12+

27 Zr tetrameric cations intercalated into vermiculite Zr-tetrameric complex [Zr 4 (OH) 8 (H2O) 16 ] 8+ coordinated with 8 water molecules in the interlayer space of vermiculite.

28 Zr tetrameric cations intercalated into vermiculite Two [Zr 4 (OH) 14 (H2O) 10 ] 2+ tetrameric cations, two Mg 2+ cations and ten water molecules in the interlayer space of vermiculite.

29 Zr tetrameric cations intercalated into vermiculite

30 Zr tetrameric cations intercalated into vermiculite The basal spacing d(002), the length c and the angle β of optimized models are similar to the characteristics obtained from the XRD measurement of the real sample.

31 Zr tetrameric cations intercalated into vermiculite Amount of water predicted by molecular modeling is lower than the amount calculated from the TG mass loss of the real Zr 4+ vermiculite sample.

32 Zr tetrameric cations intercalated into vermiculite While the 8.6 wt.% of water per unit cell in the real sample is an average value, the wt.% of water in models per supercell represents the amount of water in the vicinity of Zr-tetrameric cations. Taking into account the non-uniform distribution of the interlayer material it is probable that the amount of water at the sites with the lack of the Zr-tetrameric cations can be significantly higher.

33 vermiculite filler in polyethylene blend M. Valášková, J. Tokarský, K. Čech Barabaszová, V. Matějka, M. Hundáková, E. Pazdziora, D. Kimmer: New aspects on vermiculite filler in polyethylene. Applied Clay Science 72 (2013)

34 vermiculite filler in polyethylene blend XRD patterns of real vermiculite (VER) and vermiculite/polyethylene (VER/PE) samples.

35 vermiculite filler in polyethylene blend Results of molecular modeling. XRD patterns of real vermiculite (VER) and vermiculite/polyethylene (VER/PE) samples.

36 vermiculite filler in polyethylene blend Results of molecular modeling. XRD patterns of real vermiculite (VER) and vermiculite/polyethylene (VER/PE) samples.

37 vermiculite filler in polyethylene blend

38 vermiculite filler in polyethylene blend When C=C bond is present in the end of PE chain, the H atom tends to get close to the OH groups in the vermiculite structure. The mutual C=CH 2 HO distance was found to be nm and the angle was very close to 170. This attractive interaction is similar to a weak carbon-donor hydrogen bond described in He et al. Prog. Polym. Sci. 29 (2004)

39 biodegradable polymers as a drug carriers M. Macháčková, J. Tokarský, P. Čapková: A simple molecular modeling method for the characterization of polymeric drug carriers. European Journal of Pharmaceutical Sciences 48 (2013)

40 biodegradable polymers as a drug carriers Six biodegradable polymers have been investigated as a drug carriers using molecular simulations in Materials Studio modeling environment. L-polylactide (L-PLA) D-polylactide (D-PLA) chitosan (Ch) polyglycolic acid (PGA) polyethylene glycol (PEG) cellulose (Ce) Pristine polymer chains and drug-polymer systems were studied and compared In order to characterize the suitability of a given polymer chain for non-bond anchoring of drug molecule.

41 biodegradable polymers as a drug carriers model drug Cyclosporine A

42 biodegradable polymers as a drug carriers model drug Cyclosporine A (CsA)

43 biodegradable polymers as a drug carriers model drug Cyclosporine A fungus Tolypocladium inflatum

44 biodegradable polymers as a drug carriers energy characteristics 1) mutual drug/polymer miscibility ( parameter) 2) non-bond interaction energy between CsA and polymer structural parameters 3) flexibility change of the gyration radius (R g /R g0 ) 4) number of H-bonds between CsA and polymer

45 biodegradable polymers as a drug carriers Miscibility described by parameter is in the 1 st column. The 2 nd column shows the flexibility of polymer in presence of CsA (R g /R g0 ). Polymer-CsA non-bond interaction energies E int and the numbers of H bonds between the polymer and CsA are in the 3 rd and 4 th column, respectively.

46 biodegradable polymers as a drug carriers Miscibility described by parameter is in the 1 st column. The 2 nd column shows the flexibility of polymer in presence of CsA (R g /R g0 ). Polymer-CsA non-bond interaction energies E int and the numbers of H bonds between the polymer and CsA are in the 3 rd and 4 th column, respectively.

47 biodegradable polymers as a drug carriers The lowest interaction energy frame (left) and optimized structure (right) for each polymer/csa system. Because of clarity the polymer chains are green and CsA molecules are blue in optimized models (right).

48 biodegradable polymers as a drug carriers The best miscibility is strongly correlated with the polymer-csa interaction energy and with the number of H-bonds. Ce and Ch with the best miscibility and highest polymer-drug adhesion exhibit high rigidity (i.e. high value of R g /R g0 ratio). Molecular modeling results are in good agreement with experimental data found in literature.

49 biodegradable polymers as a drug carriers Our characterization method revealed Ch and Ce to be very promising drug carriers and there are many experimental confirmations of this fact. Ch and Ce are frequently used polymeric drug carriers H.S. Kas, et al., J. Microencapsul. 14 (1997) L. Illum, Pharm. Res. 15 (1998) C. Remuňán-López, et al. Eur. J.Pharm. Biopharm. 45 (1998) A.M. De Campos, et al. Int. J. Pharm. 224 (2001) H.C. Yang, and M.H. Hon, Microchem. J. 92 (2009) B. Wilson, et al. Nanomed.-Nanotechnol. 6 (2010) W.E. Rudzinski, and T.M. Aminabhavi, Int. J. Pharm. 399 (2010) and many others

50 biodegradable polymers as a drug carriers Our characterization method revealed that PEG exhibits low interaction with drug molecule and bad miscibility. experimental confirmation T. Tajiri, et al. Int. J. Pharm. 395 (2010) The release mechanism from polymer matrices containing PEO and PEG in various weight ratios was studied. The higher the concentration of PEG, the faster release. J. Matsumoto, et al. Int. J. Pharm. 185 (1999) The amount released from PLA-PEG-PLA copolymer was greater with the higher PEG content. R. Gref, et al. Eur. J. Pharm. Biopharm. 51 (2001) PLA-PEG copolymer enables easier release than PLA homopolymer.

51 biodegradable polymers as a drug carriers Our characterization method shows that PLA and PGA exhibit very similar characteristics. M.L. Hans, A.M. Lowman. Curr. Opin. Solid State Mater Sci. 6 (2002) S. Fredenberg, et al. Int. J. Pharm. 415 (2011) PLA and PGA are commonly used as their co-polymer poly(lactide-co-glycolide). W. Lee, et al. J. Controlled Release 84 (2002) In case of PGA/PLGA nanoparticles the CsA release rates are not dependent on the ratio of PLA and PGA in the PLGA copolymer.

52 Thank You for Your attention.