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  • Unexpected Intermolecular C-H···O Hydrogen Bonds and 1 H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs
Title: Unexpected Intermolecular C-H···O Hydrogen Bonds and 1 H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs
The compound 2-(((trifluoromethyl)sulfonyl)oxy)propane-1,3-diyl bis(4-methylben-zenesulfonate) (TPB) is a crucial intermediate in the synthesis of 18F radiolabeled cromolyn derivatives. In this work, we combine 1H NMR spectroscopy, X-ray crystallography, ab initio molecular dynamics and NMR calculations to examine the structure, interactions and solvation dynamics of the TPB molecule. In CDCl3, the -CH2 groups within its glyceryl-derived linker exhibit a single set of proton signals in the 1H NMR measurements. However, when TPB is dissolved in DMSO-d6, distinct splitting patterns emerge despite its seemingly symmetric chemical structure. Crystallographic analysis further unveils the absence of overall symmetry in its three-dimensional arrangement. To elucidate these unique NMR features, we carry out ab initio molecular dynamics simulations and characterize the solvation structures and dynamics of TPB in CHCl3 and DMSO solutions. In contrast to the predominantly non-polar nature of the CHCl3 solvents, DMSO directly participates in C-H···O hydrogen bonding interactions with the solute molecule, leading to the splitting of its -CH2 chemical shifts into two distinct distributions. The comprehensive understanding of the structure and solvation interactions of TPB provides essential insights for its application in the radiofluorination reactions of cromolyn derivatives and holds promise for the future development of radiolabeled dimeric drugs.  more » « less
Award ID(s):
1904800
PAR ID:
10532813
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
American Chemical Society
Date Published:
Journal Name:
The Journal of Physical Chemistry B
Volume:
128
Issue:
22
ISSN:
1520-6106
Page Range / eLocation ID:
5454 to 5462
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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