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Towards Selective Recognition of Sialic Acid Through Simultaneous Binding to Its cis ‐Diol and Carboxylate Functions
Author(s) -
RegueiroFigueroa Martín,
Djanashvili Kristina,
EstebanGómez David,
de Blas Andrés,
PlatasIglesias Carlos,
RodríguezBlas Teresa
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000186
Subject(s) - chemistry , phenylboronic acid , moiety , sialic acid , carboxylate , thiourea , hydrogen bond , stereochemistry , monosaccharide , diol , urea , molecular recognition , organic chemistry , molecule , biochemistry , catalysis
A series of receptors containing phenylboronic acid and urea or thiourea units have been designed for simultaneous recognition of the cis ‐diol and carboxylate functions of sialic acids, which are known to be overexpressed on the surfaces of tumor cells. The interaction of the receptors with 5‐acetylneuraminic acid (Neu5Ac) and 2‐α‐ O ‐methyl Neu5Ac (MeNeu5Ac) in DMSO solution has been investigated bymeans of spectrophotometric titrations and 1 H, 13 C, and 11 B NMR spectroscopy. Additionally, we have also investigated the binding of these receptors with competing monosaccharides such as D ‐(+)‐glucose, D ‐fructose, methyl α‐ D ‐galactoside, and methyl α‐ D ‐mannoside. Our results show that 2‐{[3‐(4‐nitrophenyl)thioureido]methyl}phenylboronic acid ( 3a ) recognizes both Neu5Ac and MeNeu5Ac with good selectivity with regard to the remaining monosaccharides investigated. DFT calculations performed at the B3LYP/6‐31G(d) level show that this selectivity is due to a cooperative two‐site binding of Neu5Ac through 1) ester formation by interaction at the phenylboronic acid function of the receptor and 2) hydrogen‐bond interaction between the thiourea moiety and the carboxylate group of Neu5Ac. Compound 3a can therefore be considered a promising synthon for the design of contrast agents for magnetic resonance imaging of tumors. In contrast, the analogue of 3a containing a urea moiety – compound 3b – displays strong binding to all monosaccharides investigated, due to two‐site binding through interaction on the phenylboronic acid function of the receptor and a hydrogen‐bond interaction between the urea moiety and the sugar hydroxy groups.