Synthesis of Phosphonated Polyphosphazenes via Two Synthetic Routes

Abstract

Reagents. Tetrahydrofuran and triethylamine (EMD) were dried using solvent purification columns, and the final water content was monitored by Karl Fisher titration. 26 Ethanol and acetonitrile (EMD) were distilled from sodium metal and stored over molecular sieves (4Å) before use. Dichloromethane (EMD), methanol (EMD), hexanes (EMD), ethyl acetate (EMD), alanine ethyl ester hydrochloride (Chem Impex), phenylalanine ethyl ester hydrochloride (Chem Impex), sodium (Sigma), tyramine (TCI), ditert butyl dicarbonate (Sigma), sodium bicarbonate (Sigma), diethyl vinylphosphonate (TCI), ferulic acid (Sigma), trifluoroacetic acid (Sigma), sodium iodide (Aldrich), and trimethylsilyl chloride (Fluka) were used as received. Spectra/Por molecular porous cellulose dialysis membranes with a molecular weight cutoff of 12,000-14,000 were used for purification of the polymers.Equipment. 31 P and 1 H NMR spectra were obtained with a Bruker 360 WM instrument operated at 145 MHz and 360 MHz, respectively. 31 P shifts are reported in ppm relative to 85% H 3 PO 4 at 0 ppm. Glass transition temperatures were measured with a TA Instruments Q10 differential scanning calorimetry apparatus with a heating rate of 10 °C/min and a sample size of ca. 10 mg. Gel permeation chromatography was performed using a Hewlett-Packard 1047A refractive index detector and two Phenomenex Phenogel linear 10 columns. The samples were eluted at 1.0 mL/min with a 10 mM solution of tetra-n-butylammonium nitrate in THF. The elution times were calibrated with polystyrene standards. Mass spectrometric analyses were performed using a Waters LCT Premier time-of-flight (TOF) mass spectrometer in positive or negative ion mode, using electrospray ionization (ESI). Ultraviolet spectra were obtained with a double-beam spectrophotometer (Varian, Cary 500). Measurements were conducted in de-ionized water or in a 10 mM phosphate buffered saline solution (PBS). Synthesis of bis-(diethyl phosphonate)-N,N-diethyltyramine (DPT) and (diethyl phosphonate)-Nethyltyramine (MPT).Tyramine (1.73 g, 12.6 mmol) and diethylvinylphosphonate (3.60 g, 21.9 mmol) were dissolved in de-ionized water (160 mL) and heated at 50 °C for 48 h. The sample was cooled and extracted with DCM. The organic layers were combined and dried over magnesium sulfate. Once dry, the solvent was removed under reduced pressure and dried further under vacuum to afford the product as a crude oil. The

Characterization of hydroxyapatite deposition on biomimetic polyphosphazenes by time-of-flight secondary ion mass spectrometry (ToF-SIMS)

“…40,41 The synthetic exibility of this system has provided access to biocompatible and biodegradable polymers that show good osteocompatibility 42,43 both in vitro 44,45 and in vivo, [44][45][46] with little acute inammatory response 47 and mineral deposition. 27 More recently, a number of phosphonic acid containing polyphosphazenes have been synthesized and characterized 48 in order to generate bioactive polymers capable of inducing in situ hydroxyapatite mineralization. In this work, their ability to mineralize hydroxyapatite from a simulated body uid (SBF) solution was examined.…”

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

“…Polyphosphazenes are commonly synthesized via a two-step reaction process starting from the commercially available cyclic trimer hexachlorocyclotriphosphazene (HCCTP). The first step involves the synthesis of linear PDCP which can be achieved via the controlled thermal ring opening polymerization of cyclic trimer at 250°C under vacuum [4, 10, 15, 21, 32, 37, 39, 40, 42, 44, 49, 56, 58-60]. This reaction is usually carried out under vacuum in a sealed glass tube at high temperatures; typically 250 °C for several hours.…”

Deposition of calcium hydroxyapatite on negatively charged polyphosphazene surfaces

“…Additionally, the hydrolytic breakdown is further facilitated by the hydrolytically labile nature of the PN bond linking the side group to the polymer backbone, which has been shown to be hydrolytically unstable even in the absence of acidic side groups . These hydrolysis rates are also significantly higher than those measured for the previously published phosphonic acid system, and can be explained by the significantly higher loading of acidic side groups in these polymers.…”

“…Previous work has shown that polyphosphazenes with biologically compatible side groups are biocompatible, have highly tunable rates of hydrolytic breakdown and are capable of producing a minimal inflammatory response when implanted in vivo . More recently, we have investigated polyphosphazenes containing phosphonic acid functionalized side groups, in an attempt to generate materials capable of nucleating the growth of hydroxyapatite during exposure to SBF . Although these materials were shown to have hydroxyapatite deposits on their surface, the coatings were sparse, with very little HAp deposited during the 4 week trial.…”