Polyphosphazenes For Biomedical Applications

Author : Jessica Kroger
Publisher :
ISBN 13 :
Total Pages : 153 pages
Book Rating : 4.:/5 (816 download)

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Download or read book Computational Chemistry and Molecular Modeling of Polyphosphazenes for Biomedical Applications written by Jessica Kroger and published by . This book was released on 2012 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polyphosphazenes are a unique class of polymers whose properties are attractive for a variety of biomedical applications. Consisting of a backbone of alternating phosphorus and nitrogen atoms with organic side groups attached to the phosphorus, polyphosphazenes are specifically advantageous for drug delivery which can exploit the backbone's sensitivity to hydrolytic degradation. Unfortunately, characteristic data of these polymers and the mechanisms driving hydrolysis are limited in the literature. In this study, computational chemistry and molecular modeling were used to investigate polyphosphazenes from a theoretical perspective. Properties of four biomedically relevant polyphosphazenes poly(dichlorophosphazene) (PDCP), poly(glycineethylesterphosphazene) (PGEEP), poly[bis(carboxylatophenoxy)phosphazene] (PCPP) and poly[di(imidazole)phosphazene] (PDIP) were investigated by molecular dynamics simulations. The densities obtained for these polymers ranged from 1.269 (PGEEP) to 2.174 (crystalline PDCP) g/cm3. As validation of the simulation results, the glass transition temperature of PGEEP was estimated to be 255 K, in agreement with experimental results. Radial distribution functions showed evidence of hydrogen bonding in amorphous PCPP, but little or no hydrogen bonding was observed in the remaining polymers. Hydrogen bonding leads to increased electrostatic interactions in amorphous PCPP, as evidenced by the largersolubility parameter of 19.082 (J/cm3)1/2 obtained for PCPP compared to 14.437, 13.928, and 14.647 (J/cm3)1/2 for amorphous PDCP, PGEEP and PDIP, respectively. Time-correlation functions were calculated for each polymer to determine the relative flexibility of the backbones and side-groups of each polyphosphazene. The backbones and side-groups of both amorphous PDCP and PGEEP show significant flexibility while those of amorphous PCPP and PDIP show more limited motions. Density functional theory (DFT) calculations, including the ab initio molecular dynamics method, atom-centered density matrix propagation (ADMP), were used to investigate the hydrolysis reaction of a dichlorophosphazene (DCP) trimer. The model trimer, intermediate structures and the product of the first step of hydrolysis, were optimized using density functional theory (DFT) with the B3LYP density functional, followed by a 600 fs ADMP simulation. Natural bond order analysis (NBO) was used to determine atomic charges and electron occupancy of the bond orbitals and the lone pair orbitals of the molecule at various points along the simulation pathway. The simulation successfully shows dissociation of the trimer backbone into two distinct product molecules, shown through both increasing separation of the product units and through the more thorough NBO analysis of the bond orbitals.