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Suppression of Problematic Compound Oligomerization by Cosolubilization of Nondetergent Sulfobetaines
Author(s) -
Mizukoshi Yumiko,
Takeuchi Koh,
Arutaki Misa,
Takizawa Takeshi,
Hanzawa Hiroyuki,
Takahashi Hideo,
Shimada Ichio
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500057
Subject(s) - chemistry , monomer , nuclear magnetic resonance spectroscopy , oligomer , relaxation (psychology) , aqueous solution , two dimensional nuclear magnetic resonance spectroscopy , equilibrium constant , dynamic equilibrium , stereochemistry , polymer , organic chemistry , social psychology , psychology
Numerous small organic compounds exist in equilibrium among monomers, soluble oligomers, and insoluble aggregates in aqueous solution. Compound aggregation is a major reason for false positives in drug screening, and even soluble oligomers can interfere with structural and biochemical analyses. However, an efficient way to manage the equilibrium of aggregation‐prone compounds, especially those involved with soluble oligomers, has not been established. In this study, solution NMR spectroscopy was used as a suitable technique to detect compound oligomers in equilibrium, and it was demonstrated that cosolubilization of nondetergent sulfobetaines (NDSBs) can largely suppress compound oligomerization and aggregation by shifting the equilibrium toward the monomers. The rotational correlation time was obtained from the ratio of the selective and nonselective longitudinal NMR relaxation times, which directly and quantitatively reflected the apparent sizes of the compounds in the equilibrium. The rotational correlation time of the aggregation‐prone compound SKF86002 (1 m M ) was substantially reduced from 0.31 to 0.23 ns by cosolubilization of 100 m M NDSB195. NDSB cosolubilization allowed us to perform successful structural and biochemical experiments with substantially fewer artifacts, which represents a strategy to directly resolve the problematic oligomerization and aggregation of compounds.