title: Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers.
abstract: 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.
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Davit
authors.initials: D
authors.lastname: Jishkariani
authors.affiliation: Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122.
authors.forename: Christopher M
authors.identifier: 0000-0003-2376-8867
authors.initials: CM
authors.lastname: MacDermaid
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Yam N
authors.initials: YN
authors.lastname: Timsina
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Silvia
authors.initials: S
authors.lastname: Grama
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Syeda S
authors.initials: SS
authors.lastname: Gillani
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Divar
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6313.
authors.forename: Srujana S
authors.initials: SS
authors.lastname: Yadavalli
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Ralph-Olivier
authors.initials: RO
authors.lastname: Moussodia
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Pawaret
authors.initials: P
authors.lastname: Leowanawat
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
authors.forename: Angely M
authors.initials: AM
authors.lastname: Berrios Camacho
authors.affiliation: Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Walter
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6313.
authors.forename: Mark
authors.initials: M
authors.lastname: Goulian
authors.affiliation: Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122; percec@sas.upenn.edu mlklein@temple.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323; percec@sas.upenn.edu mlklein@temple.edu.
authors.forename: Virgil
authors.initials: V
authors.lastname: Percec
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005029:Ethylenediamines / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry; D009757:Nylons / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D050091:Dendrimers; D005029:Ethylenediamines; D009757:Nylons; C031234:ethylenediamine
keywords: antimicrobials; dendrons; ethylenediamine core; nanomedicine; piperazine core