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Jishkariani D , MacDermaid CM , Timsina YN , Grama S , Gillani SS , Divar M , Yadavalli SS , Moussodia RO , Leowanawat P , Berrios Camacho AM , Walter R , Goulian M , Klein ML , Percec V
Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12) :E2275-e2284
PMID: 28270599    PMCID: PMC5373347   
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2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl)propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent-divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2-bis(aminomethyl)propionate (COOMe) cores. These cores have the same multiplicity but different conformations. A diversity of synthetic methods were used for the synthesis of dendrimers and dendrons. Regardless of the method used, a self-interruption of the synthesis was observed at generation 4 for the dendrimer with an EDA core and at generation 5 for the one with a PPZ core, whereas for the COOMe core, self-interruption was observed at generation 6 dendron, which is equivalent to generation 5 dendrimer. Molecular modeling and molecular-dynamics simulations demonstrated that the observed self-interruption is determined by the backfolding of the azide groups at the periphery of the dendrimer. The latter conformation inhibits completely the heterogeneous hydrogenation of the azide groups catalyzed by 10% Pd/carbon as well as homogeneous hydrogenation by the Staudinger method. These self-terminated polyamide dendrimers are enzymatically and hydrolytically stable and also exhibit antimicrobial activity. Thus, these nanoscale constructs open avenues for biomedical applications.
1091-6490 Jishkariani, Davit MacDermaid, Christopher M ORCID: http://orcid.org/0000-0003-2376-8867 Timsina, Yam N Grama, Silvia Gillani, Syeda S Divar, Masoumeh Yadavalli, Srujana S Moussodia, Ralph-Olivier Leowanawat, Pawaret Berrios Camacho, Angely M Walter, Ricardo Goulian, Mark Klein, Michael L Percec, Virgil R01 GM080279/GM/NIGMS NIH HHS/United States Journal Article United States Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):E2275-E2284. doi: 10.1073/pnas.1700922114. Epub 2017 Mar 7.