NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

Damjan Makuc,Janez Plavec,Philip A Gale,Jennifer R Hiscock,Mark E Light

doi:10.3762/bjoc.7.140

Damjan Makuc, Janez Plavec + Show 3 more

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https://doi.org/10.3762/bjoc.7.140

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Abstract

The conformational properties of 1,3-diindolylureas and thioureas were studied by a combination of heteronuclear NMR spectroscopy and quantum mechanics calculations. NOE experiments showed that the anti–anti conformer along the C7–N7α bonds was predominant in DMSO-d6 solution in the absence of anions. Anion-induced changes in the 1H and 15N chemical shifts confirm the weak binding of chloride anions with negligible conformational changes. Strong deshielding of ureido protons and moderate deshielding of indole NH was observed upon the addition of acetate, benzoate, bicarbonate and dihydrogen phosphate, which indicated that the predominant hydrogen bond interactions occurred at the urea donor groups. Binding of oxo-anions caused conformational changes along the C7–N7α bonds and the syn–syn conformer was preferred for anion–receptor complexes. The conformational changes upon anion binding are in good agreement with energetic preferences established by ab initio calculations.

Highlights

In the last two decades, remarkable efforts have been made in the field of the development of synthetic anion receptors, motivated by prospective applications in recognition, separation, guest inclusion and catalysis [1,2,3,4,5,6,7,8,9,10,11,12,13]
The bis-indole receptors 1–4 were characterized by heteronuclear NMR spectroscopy
NOE based conformational analysis was supported by quantum mechanics calculations and revealed that diindolylurea 1 exhibited conformational preorganization in DMSO-d6 solution

Summary

Introduction

In the last two decades, remarkable efforts have been made in the field of the development of synthetic anion receptors, motivated by prospective applications in recognition, separation, guest inclusion and catalysis [1,2,3,4,5,6,7,8,9,10,11,12,13]. Indole contains a single hydrogen bond donor group, which is employed in biological systems to bind anions such as chloride [32] and sulfate [14]. Indole and urea groups were strongly involved in hydrogen-bonding interactions with the bound anionic guest, whilst the amide group interacted only weakly with the bound anion. These observations led to the design of diindolylureas and diindolylthioureas [36,37,38]. Whilst the conformational properties of these compounds have been explored by single crystal X-ray diffraction in the solid-state, a detailed analysis of the conformational properties of the these compounds in solution, in the absence and presence of oxo-anions,

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Conclusion