Oxazoline amino acid bioconjugates: one-pot synthesis and analysis of supramolecular interactions

Bakija, Marija; Perić, Berislav; Kirin, Srećko I. (2024) Oxazoline amino acid bioconjugates: one-pot synthesis and analysis of supramolecular interactions. New Journal of Chemistry, 48 (19). pp. 8702-8719. ISSN 1144-0546

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Abstract

This publication describes oxazoline-amino acid bioconjugates 1 capable of supramolecular interactions. The bioconjugates contain three main building blocks: an oxazoline ring, a central aromatic unit and an amino acid substituent. Benzene, naphthalene or anthracene with several substitution motifs was used as the central aromatic unit. Two synthetic pathways to beta-amino alcohol precursors 3-5 are presented; one-pot synthesis with various coupling reagents is compared to linearly sequenced synthesis using protecting groups. In the final step, a cyclization of precursors 3-5 to oxazolines 1 is described. Single crystal X-ray diffraction of seven oxazoline bioconjugates is reported (1p, 1m6, 1n2, 1n4, 1n5, 1a and 1t4), with an emphasis on supramolecular interactions in the solid state. The capability of bioconjugates 1 to participate in supramolecular interactions in solution was screened by NMR and CD spectroscopy, varying concentrations, temperatures and solvents. The results obtained by crystallography and spectroscopy were further corroborated by computational results for most interesting bioconjugate 1t1. Computational analysis was performed using a CREST/CENSO protocol. In particular, the free energy of formation, Delta G, as well as mean absolute error (MAE) values and correlations of experimental and GIAO calculated NMR parameters have been compared for 1t1 DFT models of monomers and dimers. These results revealed that for 1t1, the supramolecular dimer ensembles are more stable than monomer ensembles.

Item Type:	Article
Uncontrolled Keywords:	amides; oxazolines; hydrogen bonding; secondary structures
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Materials Chemistry
Projects:	Project title Project leader Project code Project type Inovativna rješenja u katalitičkim proizvodnim procesima za potrebe farmaceutske industrije-CAT PHARMA Srećko Kirin KK.01.1.1.04.0013 EK Supramolekulska asimetrična kataliza: Prijenos kiralnosti u koordinacijskim kavezima UNSPECIFIED UNSPECIFIED UNSPECIFIED
Depositing User:	Marija Bakija
Date Deposited:	25 Jul 2024 12:07
URI:	http://fulir.irb.hr/id/eprint/8969
DOI:	10.1039/d4nj00995a

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