Ron Scozzafava | Massachusetts Institute of Technology (MIT) (original) (raw)
Papers by Ron Scozzafava
Macromolecules, 1988
Two approaches for one-step solution polymerization of poly(anhydrides) at ambient temperature we... more Two approaches for one-step solution polymerization of poly(anhydrides) at ambient temperature were developed. In the first approach highly pure polymers (>99.7%) were obtained by the use of sebacoyl chloride, phosgene, or diphosgene as coupling agents and poly(4-vinylpyridine) or K&03 as insoluble acid acceptors. In this approach, the polymer is exclusively soluble in the reaction solution and the only byproduct formed is the insoluble acid acceptor-hydrochloric acid salt. Polymerization of sebacic acid with phosgene, either as a gas or in solution, or diphosgene as a coupling agent with triethylamine as an acid acceptor yielded a polyanhydride with a weight average molecular weight up to 16300. This polybhydride) was contaminated with EbN-HCl (up to 80%, mol %). The use of insoluble acid acceptors gave pure polymers (>99.7%) with a weight average molecular weight up to 13 950. The second approach for one-step synthesis of pure poly-(anhydrides) was the use of an appropriate solvent where the polymer is exclusively soluble but the corresponding polymerization byproduct (e.g., Et3N.HC1) is insoluble. Under this condition polymerization of sebacic acid gave the best results in NJV-dimethylformamide and in toluene.
Journal of the American Chemical Society, 1985
Intermolecular kinetic isotope effects with 2,3-dimethyl-2-butene and methylenecyclohexane and in... more Intermolecular kinetic isotope effects with 2,3-dimethyl-2-butene and methylenecyclohexane and intramolecular isotope effects with gem-, trans-, and cis-2,3-dimethyl-2-butene-d6 establish that the Lewis acid catalyzed ene reactions of methyl propiolate, formaldehyde, and diethyl oxomalonate proceed through a stepwise reaction with rate-determining formation of either (1) a three-membered ring intermediate lacking the geometrical rigidity of perepoxides and related intermediates, (2) a pair of rapidly equilibrating zwitterions, or (3) a n-complex between the ene component and enophile-Lewis acid complex. The intermolecular isotope effects are small and the intramolecular isotope effects with 2 and 3 are large, indicating that the reaction is stepwise. The large intramolecular isotope effects with 1 require that the reaction proceeds through an intermediate that can abstract a hydrogen from either end of the ene component, Le., one of the three possibilities mentioned above. The ene reaction traditionally has been thought to proceed through either a concerted pericyclic reaction (eq 1) or a stepwise reaction with a zwitterionic or diradical intermediate (eq 2).2 Each of these mechanisms has been established in specific cases. Recent studies have indicated that the ene reaction is mechanistically more diverse. Stephenson has developed a stereochemical isotope test comparing intermolecular kinetic isotope effects with the intramolecular isotope effects obtained with gem-, trans-, and cis-2,3-dimethyl-2-butene-d6 (1, 2, and 3, re~pectively).~ The use of this isotope test demonstrated that singlet oxygen ene reactions proceed through a third mechanism. The results, in which small isotope effects of m1.05 are obtained with 3 and in intermolecular competitions and larger isotope effects of ~1. 4 are obtained with 1 and 2, indicate not only that the reactions is stepwise but that it proceeds through a perepoxide-like intermediate which only allows competitive hydrogen abstraction from cis groupings of C-H bonds (eq 3). Seymour and Greene have used isotope effects obtained with 1, 2, and 3 to establish that the ene reactions of triazolinediones and pentafluoronitrosobenzene show similar stereochemical effects and therefore proceed through aziridinium imide and aziridine N-oxide intermediates, respect i~e l y .~.~ Kwart and Brechbiel have explored the temperature dependence of kinetic isotope effects in ene reactions and claimed that the
![Research paper thumbnail of Type II intramolecular [2 + 2] cycloadditions of alkenes with alkylvinylketenes. Synthesis of methyl jasmonate](https://attachments.academia-assets.com/95219844/thumbnails/1.jpg)
](The Journal of Organic Chemistry, 1988
The Journal of Organic Chemistry, 1987
Journal of the American Chemical Society, 1990
... Hydrolytically Degradable Amino Acid Containing Polymers ... mation. Higher molecular weights... more ... Hydrolytically Degradable Amino Acid Containing Polymers ... mation. Higher molecular weights in shorter time were generally obtained by addition of catalysts such as earth metal oxides andmetal salts, whereas alkoxy metals caused a decrease in molecular weight. ...
Journal of Controlled Release, 1996
Autografting is the most common treatment to correct osseous defects, with donor sites of calvari... more Autografting is the most common treatment to correct osseous defects, with donor sites of calvarium, iliac crest, and rib used most often [1]. While varying degrees of 'success' have been reported with this therapy, a universal concern is donor site morbidity. Allogeneic bank bone is an alternative to the autograft and while donor site morbidity is not an issue, bank bone has liabilities that make it less effective than the autograft. Therefore, an off-the-shelf product to replace these therapies would improve the quality of care for patients. Towards the development of such a product, we report on two studies that assessed a combination of recombinant human bone morphogenetic protein-2 delivered to osseous wound sites with a poly(c~-hydroxy acid) carrier: poly(lactide-co-glycolide). Results from these studies indicate bone repair can be accomplished with this combination. However, despite a rich therapeutic promise, clinical utility must be amplified. Therefore, the focus of our attention in the future will be the delivery system.
Macromolecules, 1988
Two approaches for one-step solution polymerization of poly(anhydrides) at ambient temperature we... more Two approaches for one-step solution polymerization of poly(anhydrides) at ambient temperature were developed. In the first approach highly pure polymers (>99.7%) were obtained by the use of sebacoyl chloride, phosgene, or diphosgene as coupling agents and poly(4-vinylpyridine) or K&03 as insoluble acid acceptors. In this approach, the polymer is exclusively soluble in the reaction solution and the only byproduct formed is the insoluble acid acceptor-hydrochloric acid salt. Polymerization of sebacic acid with phosgene, either as a gas or in solution, or diphosgene as a coupling agent with triethylamine as an acid acceptor yielded a polyanhydride with a weight average molecular weight up to 16300. This polybhydride) was contaminated with EbN-HCl (up to 80%, mol %). The use of insoluble acid acceptors gave pure polymers (>99.7%) with a weight average molecular weight up to 13 950. The second approach for one-step synthesis of pure poly-(anhydrides) was the use of an appropriate solvent where the polymer is exclusively soluble but the corresponding polymerization byproduct (e.g., Et3N.HC1) is insoluble. Under this condition polymerization of sebacic acid gave the best results in NJV-dimethylformamide and in toluene.
Journal of the American Chemical Society, 1985
Intermolecular kinetic isotope effects with 2,3-dimethyl-2-butene and methylenecyclohexane and in... more Intermolecular kinetic isotope effects with 2,3-dimethyl-2-butene and methylenecyclohexane and intramolecular isotope effects with gem-, trans-, and cis-2,3-dimethyl-2-butene-d6 establish that the Lewis acid catalyzed ene reactions of methyl propiolate, formaldehyde, and diethyl oxomalonate proceed through a stepwise reaction with rate-determining formation of either (1) a three-membered ring intermediate lacking the geometrical rigidity of perepoxides and related intermediates, (2) a pair of rapidly equilibrating zwitterions, or (3) a n-complex between the ene component and enophile-Lewis acid complex. The intermolecular isotope effects are small and the intramolecular isotope effects with 2 and 3 are large, indicating that the reaction is stepwise. The large intramolecular isotope effects with 1 require that the reaction proceeds through an intermediate that can abstract a hydrogen from either end of the ene component, Le., one of the three possibilities mentioned above. The ene reaction traditionally has been thought to proceed through either a concerted pericyclic reaction (eq 1) or a stepwise reaction with a zwitterionic or diradical intermediate (eq 2).2 Each of these mechanisms has been established in specific cases. Recent studies have indicated that the ene reaction is mechanistically more diverse. Stephenson has developed a stereochemical isotope test comparing intermolecular kinetic isotope effects with the intramolecular isotope effects obtained with gem-, trans-, and cis-2,3-dimethyl-2-butene-d6 (1, 2, and 3, re~pectively).~ The use of this isotope test demonstrated that singlet oxygen ene reactions proceed through a third mechanism. The results, in which small isotope effects of m1.05 are obtained with 3 and in intermolecular competitions and larger isotope effects of ~1. 4 are obtained with 1 and 2, indicate not only that the reactions is stepwise but that it proceeds through a perepoxide-like intermediate which only allows competitive hydrogen abstraction from cis groupings of C-H bonds (eq 3). Seymour and Greene have used isotope effects obtained with 1, 2, and 3 to establish that the ene reactions of triazolinediones and pentafluoronitrosobenzene show similar stereochemical effects and therefore proceed through aziridinium imide and aziridine N-oxide intermediates, respect i~e l y .~.~ Kwart and Brechbiel have explored the temperature dependence of kinetic isotope effects in ene reactions and claimed that the
The Journal of Organic Chemistry, 1988
The Journal of Organic Chemistry, 1987
Journal of the American Chemical Society, 1990
... Hydrolytically Degradable Amino Acid Containing Polymers ... mation. Higher molecular weights... more ... Hydrolytically Degradable Amino Acid Containing Polymers ... mation. Higher molecular weights in shorter time were generally obtained by addition of catalysts such as earth metal oxides andmetal salts, whereas alkoxy metals caused a decrease in molecular weight. ...
Journal of Controlled Release, 1996
Autografting is the most common treatment to correct osseous defects, with donor sites of calvari... more Autografting is the most common treatment to correct osseous defects, with donor sites of calvarium, iliac crest, and rib used most often [1]. While varying degrees of 'success' have been reported with this therapy, a universal concern is donor site morbidity. Allogeneic bank bone is an alternative to the autograft and while donor site morbidity is not an issue, bank bone has liabilities that make it less effective than the autograft. Therefore, an off-the-shelf product to replace these therapies would improve the quality of care for patients. Towards the development of such a product, we report on two studies that assessed a combination of recombinant human bone morphogenetic protein-2 delivered to osseous wound sites with a poly(c~-hydroxy acid) carrier: poly(lactide-co-glycolide). Results from these studies indicate bone repair can be accomplished with this combination. However, despite a rich therapeutic promise, clinical utility must be amplified. Therefore, the focus of our attention in the future will be the delivery system.