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We present a new class of compounds that enable fast and controlled Ring\u2010Opening Polymerization (ROP) of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010carboxyanhydrides (NCAs) under ambient, open\u2010vessel conditions.\n                    <jats:italic>N<\/jats:italic>\n                    \u2010heterocyclic azamacrocycles allow for polymerization of \u03b3\u2010benzyl\u2010\n                    <jats:italic>L<\/jats:italic>\n                    \u2010glutamate (BLG), sarcosine (SAR), and\n                    <jats:italic>\u03b5<\/jats:italic>\n                    \u2010benzyloxycarbonyl\u2010\n                    <jats:italic>L<\/jats:italic>\n                    \u2010lysine\n                    <jats:italic>N<\/jats:italic>\n                    \u2010carboxyanhydride (ZLYS) with dispersities as low as\n                    <jats:italic>\u0110<\/jats:italic>\n                    \u22481.1 for both low and high targeted degrees of polymerization (DP\n                    <jats:sub>T<\/jats:sub>\n                    \u223c20 to 1000). Degree of methylation of the macrocycle modulates their final role in ROP\u2010NCA: the fully\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methylated azamacrocycle N\n                    <jats:sub>14<\/jats:sub>\n                    Me\n                    <jats:sub>3<\/jats:sub>\n                    acts predominantly as an external rate\u2010enhancing catalyst under the tested external nucleophile conditions, while partially methylated N\n                    <jats:sub>14<\/jats:sub>\n                    Me\n                    <jats:sub>1<\/jats:sub>\n                    analogue exhibits dual initiator\u2010catalyst (IniCat) behavior. Kinetic studies and DFT calculations support cooperative participation of the azamacrocyclic scaffold and identify plausible accelerated amine mechanism via monomer activation (AAMMA)\u2010related pathways involving secondary\u2010sphere stabilization of reactive species. The combined results indicate a dynamically evolving system in which the relative contributions of individual interactions may depend on monomer structure, reaction environment and chain growth, highlighting azamacrocycles as tunable platforms for facile precision polypeptide synthesis.\n                  <\/jats:p>","DOI":"10.1002\/anie.1221444","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:08:41Z","timestamp":1792663721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing Reaction Kinetics and Structural Control in\n                    <i>N<\/i>\n                    \u2010Carboxyanhydride (NCA) Polypeptide Synthesis by Structurally Tuned Azamacrocyclic Ligands"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8506-7102","authenticated-orcid":false,"given":"Paulina","family":"Maksym","sequence":"first","affiliation":[{"name":"Department of Chemistry RCSI University of Medicine and Health Sciences  Dublin 2 Ireland"},{"name":"Institute of Physics University of Silesia in Katowice Chorz\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3930-8489","authenticated-orcid":false,"given":"Adam","family":"Gorczynski","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Adam Mickiewicz University Pozna\u0144 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3147-3196","authenticated-orcid":false,"given":"Robert D.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Chemistry RCSI University of Medicine and Health Sciences  Dublin 2 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca Bartolini","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Chemistry RCSI University of Medicine and Health Sciences  Dublin 2 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