(Trimethylsilyl)ethoxyacetylene as a Dehydrating Agent for Polyanhydride Synthesis

Qian, Huanyan; Mathiowitz, Edith

doi:10.1021/ma071188a

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…Bioactive‐based PAEs, are polymer systems in which bioactives are incorporated into the polymer backbone and thus posses high bioactive‐loading, offering a means to overcome low payload associated with traditional drug‐eluting polymers . Similar to polyanhydrides, PAEs are commonly synthesized via melt‐condensation polymerization and triphosgene‐mediated solution polymerization, and with the most recent development established by Qian and Mathiowitz in 2007 using (trimethylsilyl)ethoxyacetylene as a mild dehydrating agent . Thus, to enhance synthetic efficiency, minimize waste, and improve atom economy our group sought to apply the idea of multicomponent reactions, in which multiple sequential reactions are occurring in one‐pot in high convergence, to improve our bioactive‐based PAE syntheses.…”

Section: Introductionmentioning

confidence: 99%

One‐Pot Polymerization Syntheses: Incorporating Bioactives into Poly(anhydride‐esters)

Faig

Smith

Moretti

et al. 2016

Macro Chemistry & Physics

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To reduce raw material consumption and increase synthetic efficiency, bioactive‐based poly(anhydride‐esters) containing aliphatic dicarboxylic acid‐linkages and bioactives, salicylic and p‐hydroxybenzyl acid, are synthesized via one‐pot melt‐condensation polymerizations. One‐pot poly(anhydride‐esters) physicochemical characteristics, molecular weight, and thermal properties are analyzed and compared. One‐pot salicylic acid‐based poly(anhydride‐esters) are further evaluated against analogous polymers synthesized via established methods, possessing statistically similar polymer and thermal properties while drastically reducing reaction time and solvent usage. Interestingly, p‐hydroxybenzyl acid‐based poly(anhydride‐ester) synthesis is temperature‐dependent, as higher reaction temperatures facilitate polyester formation. Compared to their poly(anhydride‐ester) analogs, these are found to possess improved thermal properties and higher molecular weight while. Accelerated hydrolytic degradation studies confirm complete bioactive release and polymer degradation. Furthermore, polymer cytotoxicity studies using 3T3 mouse fibroblasts show all polymers to be cytocompatible above therapeutically relevant concentrations. This method demonstrates that the synthesis of high‐yielding monomers can be followed by melt‐condensation polymerization in situ for the synthesis of polyanhydrides and their derivatives.

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Section: Introductionmentioning

confidence: 99%

One‐Pot Polymerization Syntheses: Incorporating Bioactives into Poly(anhydride‐esters)

Faig

Smith

Moretti

et al. 2016

Macro Chemistry & Physics

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“…Following polymerization methods published by Qian and Mathiowitz, TMSEA was synthesized and subsequently used as a dehydrating reagent under mild conditions to facilitate PAE ( 11 ) synthesis. 26 The formation of anhydride bonds (1825 and 1785 cm −1 ), preservation of the ester stretch (1759 cm −1 ), and absence of 9 ’s carboxylic acid stretch (1715 cm −1 ) in the IR spectra (Figure 2), in addition to the presence of all major proton peaks (Figure 1) indicated successful polymerization. GPC and thermal characterization substantiated the polymer formation, displaying a M w of 32 kDa with a PDI of 1.5, and T g = 34°C.…”

Section: Resultsmentioning

confidence: 97%

“…Poly(bisthymol tartrate succinate) (11) synthesis. Using a previously published procedure to synthesize polyanhydrides, 26 diacid 9 (1 eq) was dissolved in anhydrous DCM (1 mL/mmol diacid) in a 25-mL round-bottomed flask. Trimethylsilylethoxyacetylene (10, TMSEA, 1.1 eq) was added at RT and then the flask was capped and stirred at 40°C for 4 h. Mixture was concentrated in vacuo.…”

Section: Polymer and Polymer Precursor Synthesismentioning

confidence: 99%

Sugar-based poly (anhydride-ester) containing natural antioxidants and antimicrobials: Synthesis and formulation into polymer blends

Stebbins

Moy

Faig

et al. 2016

Journal of Bioactive and Compatible Polymers

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Thymol, a naturally occurring antioxidant and antimicrobial, is commonly researched for active packaging applications to deter food spoilage and bacterial growth. However, the high temperature necessary for processing often volatilizes the thymol, reducing its utility. To overcome this processing limitation, sugar-based poly(anhydride-esters) comprising thymol and compounds generally regarded as safe (succinic and tartaric acid) were successful prepared via mild solution polymerization methods. In vitro release studies demonstrated a sustained thymol release over 3 weeks at therapeutically relevant concentrations. Furthermore, the released thymol displayed antioxidant and antimicrobial activities as indicated by a 2,2-diphenyl-1-picrylhydrazyl radical scavenging and Kirby–Bauer disk diffusion assays, respectively. High-temperature melt blending with low-density polyethylene revealed that the chemical incorporation of thymol into a polymer backbone overcame volatility issues and maintained relevant bioactivity.

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“…Using a previously published procedure to synthesize polyanhydrides, 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 13 Yield: 85% (350 mg light tan foam). 1 …”

Section: Poly(2345-tetraibuprofen Mannitol Succinate (9) Synthesismentioning

confidence: 99%

“…TMSEA was synthesized using the procedure outlined by Qian and Mathiowitz. 37 Briefly, ethoxyacetylene (EA) solution (3.00 g, 1.0 equiv EA) was dissolved in anhydrous diethyl ether (12 mL/g) at 0 °C. Methyllithium (1.6 M in diethyl ether, 1.05 equiv) was added dropwise over 1 h. Solution continued to stir for 30 min before trimethylsilyl chloride (1.05 equiv) was added dropwise over 30 min.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Linear, Mannitol-Based Poly(anhydride-esters) with High Ibuprofen Loading and Anti-Inflammatory Activity

Stebbins

Uhrich

2015

Biomacromolecules

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Sugar alcohols, such as mannitol and xylitol, are biocompatible polyols that have been used to make highly cross-linked polyester elastomers and dendrimers for tissue engineering and drug delivery. However, research that utilizes the secondary hydroxyl groups as sites for pendant bioactive attachment and subsequent polymerization is limited. This work is the first report of a linear, completely biodegradable polymer with a sugar alcohol backbone and chemically incorporated pendant bioactives that exhibits sustained bioactive release and high bioactive loading (∼70%). With four pendant esters per repeat unit, this poly(anhydride-ester) has high loading and biodegrades into three biocompatible products: bioactive, sugar alcohol, and alkyl-based diacid. Ibuprofen serves as a representative bioactive, whereas mannitol is a representative polyol. Polymerization was achieved through reaction with (trimethylsilyl)ethoxyacetylene. Drug release via polymer degradation was quantified by high performance liquid chromatography. Additionally, a cytocompatibility study with fibroblast cells was performed to elucidate the polymer's suitability for in vivo use and a cyclooxygenase-2 (COX-2) assay was performed on the degradation media to ensure that released ibuprofen retained its anti-inflammatory activity. This work enables the future development of novel, biodegradable polymers exhibiting two key features: (i) polymer backbones with easily modified pendant groups, such as targeting moieties, and (ii) high drug loading using a multitude of bioactive classes.

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(Trimethylsilyl)ethoxyacetylene as a Dehydrating Agent for Polyanhydride Synthesis

Cited by 7 publications

References 22 publications

One‐Pot Polymerization Syntheses: Incorporating Bioactives into Poly(anhydride‐esters)

One‐Pot Polymerization Syntheses: Incorporating Bioactives into Poly(anhydride‐esters)

Sugar-based poly (anhydride-ester) containing natural antioxidants and antimicrobials: Synthesis and formulation into polymer blends

Linear, Mannitol-Based Poly(anhydride-esters) with High Ibuprofen Loading and Anti-Inflammatory Activity

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