Complexation of Anions Including Nucleotide Anions by Open‐Chain Host Compounds with Amide,Urea, and Aryl Functions

A systematical evaluation of association constants between halide, phosphate, and carboxylate anions with N‐methylformamide ( 1 ) and the related bidentate receptors 2 – 6 (derived from, e.g., phthalic acid or ethylenediamine) in CDCl₃ as solvent yielded increments of complexation free‐energy ΔΔG for each single H‐bond, which varied like, e.g., 5.1 kJ/mol (for Cl⁻), 4.0 kJ/mol (for Br⁻), 4.0 kJ/mol (for I⁻) (with values taken from Tables 1 and 2), in line with expected H‐bond strength. The observed complexation induced NH‐NMR shift (CIS) values also showed a regular change, in the case of 1 , e.g., from 5.0 to 2.8 to 2.1 ppm (Table 1), with about half of these values with the bidentate ligands (Tables 2 and 3). Tridentate hosts led to a substantial binding increase, if strain‐free convergence of all NH donor functions towards the anion was possible. The trisurea] ligand 10 yielded, even in the polar solvent DMSO, with Cl⁻ a ΔG of −21.5 kJ/mol and with Br⁻ of −10⋅5 kJ/mol, whereas with I⁻, no association was detectable. The results demonstrated that small, inexpensive, and conformationally mobile host compounds can exhibit high affinities as well as descrimination with anions, as much as more preorganized receptors do which require multistep synthesis. The corresponding adamantyl derivative 13 allowed measurements also in CDCl₃, with K=4.3⋅10⁴ M ⁻¹ for chloride (Table 7). Complexes with nucleotide anions were again particularly strong with the tridentate urea‐based ligands, the latter being optimal ligands for chloride complexation. For the association of 10 with AMP²⁻ and GMP²⁻in (D₆)DMSO, the association constants were 3⋅10⁴ M ⁻¹ (Table 8) and almost the same as with Cl⁻. In the case of the urea derivatives 17 , 18 , and 21 , containing only one phenyl or pyrenyl substituent, however, the ΔG values decreased in the order A>C>T>G (e.g. −13.6, −11.6, −7.6, −10.5 kJ/mol in the case of 17 , resp.; Table 8). In H₂O, the pyrenyl‐substituted urea derivatives allow measurements with fluorescence, and, unexpectedly, show only smaller nucleobase discrimination, with constants around 3⋅10³ M ⁻¹.