Synthesis, experimental and in silico studies of N-fluorenylmethoxycarbonyl-O-tert-butyl-Nmethyltyrosine, coupled with CSD data: A survey of interactions in the crystal structures of Fmoc amino acids

Joanna Bojarska , Milan Remko , Izabela Madura , Krzysztof Kaczmarek , Janusz Zabrocki , Wojciech M. Wolf

Abstract

Recently, fluorenylmethoxycarbonyl (Fmoc) amino acids (e.g. Fmoc tyrosine or Fmoc phenylalanine) have attracted growing interest in biomedical research and industry, with special emphasis directed towards the design and development of novel effective hydrogelators, biomaterials or therapeutics. With this in mind, a systematic knowledge of the structural and supramolecular features in recognition of those properties is essential. This work is the first comprehensive summary of noncovalent interactions combined with a library of supramolecular synthon patterns in all crystal structures of amino acids with the Fmoc moiety reported so far. Moreover, a new Fmoc-protected amino acid, namely, 2-{[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino}-3-{4-[(2-hydroxypropan- 2-yl)oxy]phenyl}propanoic acid or N-fluorenylmethoxycarbonyl-O-tertbutyl-N-methyltyrosine, Fmoc-N-Me-Tyr(t-Bu)-OH, C29H31NO5, was successfully synthesized and the structure of its unsolvated form was determined by single-crystal X-ray diffraction. The structural, conformational and energy landscape was investigated in detail by combined experimental and in silico approaches, and further compared to N-Fmoc-phenylalanine [Draper et al. (2015). CrystEngComm, 42, 8047 8057]. Geometries were optimized by the density functional theory (DFT) method either in vacuo or in solutio. The polarizable conductor calculation model was exploited for the evaluation of the hydration effect. Hirshfeld surface analysis revealed that H H, C H/H C and O H/H O interactions constitute the major contributions to the total Hirshfeld surface area in all the investigated systems. The molecular electrostatic potentials mapped over the surfaces identified the electrostatic complementarities in the crystal packing. The prediction of weak hydrogenbonded patterns via Full Interaction Maps was computed. Supramolecular motifs formed via C H O, C H , (fluorenyl)C H Cl(I), C Br (fluorenyl) and C I (fluorenyl) interactions are observed. Basic synthons, in combination with the Long-Range Synthon Aufbau Modules, further supported by energy-framework calculations, are discussed. Furthermore, the relevance of Fmoc-based supramolecular hydrogen-bonding patterns in biocomplexes are emphasized, for the first time.

Author Joanna Bojarska - [Lodz University of Technology]
Joanna Bojarska,,
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, Milan Remko - [Remedika]
Milan Remko,,
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, Izabela Madura (FC / CofIC)
Izabela Madura,,
- Chair Of Inorganic Chemistry
, Krzysztof Kaczmarek - [Lodz University of Technology]
Krzysztof Kaczmarek,,
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, Janusz Zabrocki - [Lodz University of Technology]
Janusz Zabrocki,,
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, Wojciech M. Wolf - [Lodz University of Technology]
Wojciech M. Wolf,,
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Journal seriesActa Crystallographica Section C-Structural Chemistry, [Acta crystallographica. Section C, Structural chemistry], ISSN 2053-2296
Issue year2020
Vol76
Pages328-345
ASJC Classification1604 Inorganic Chemistry; 1606 Physical and Theoretical Chemistry; 2505 Materials Chemistry; 3104 Condensed Matter Physics
DOIDOI:10.1107/S2053229620003009
Languageen angielski
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 03-09-2020, ArticleFromJournal
Publication indicators Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.855; WoS Impact Factor: 2018 = 0.93 (2) - 2018=4.36 (5)
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