Hydrogen-Bonded Complexes of Diaminopyridines and Diaminotriazines:  Opposite Effect of Acylation on Complex Stabilities

Abstract

The association behavior of several 2,4-diamino-s-triazines, 2,6-diaminopyridines, and their acylated derivatives with uracil derivatives was studied. In solution 1H-NMR and IR spectroscopy were used, and in the solid state as (co)crystals X-ray diffraction was used. Acylation of 2,6-diaminopyridine leads to an increase of the association constant in CDCl3 of the complexes with N-propylthymine from 84 to 440−920 M-1, whereas acylation of diamino-s-triazines leads to a dramatic fall in the association constant of the complexes with N-propylthymine from 890 to ca. 6 M-1. This phenomenon is related to different conformational preferences of these compounds. The amide groups in bis(acylamino)pyridines prefer a trans conformation, with the carbonyl group anti with respect to the ring nitrogen and coplanar with the aromatic ring. The amides of bis(acylamino)triazines, however, reside predominantly in a cis conformation. Repulsive secondary electrostatic interactions between the cis-amide and uracil carbonyl groups are thought to be responsible for the low association constant of complexes of bis(acylamino)triazines with uracils. The relatively high dimerization constants of bis(acylamino)triazines have been rationalized by the strong tendency to dimerize via quadruple hydrogen bonding.

Self-Assembling of cytosine nucleoside into triply-bound dimers in acid Media. A comprehensive evaluation of proton-bound pyrimidine nucleosides by electrospray tandem mass spectrometry, X-rays diffractometry, and theoretical calculations

“…On the contrary, evidence has been previously presented (vide infra) that hydrogen bondings between two homologous nucleosides is deeply affected, at least in the case of C-nucleosides, by the substituent present in the sugar moiety. Similarly, the interaction between N-1-propylthymine and acylated triazine derivatives is affected by conformational equilibria [43].…”

Synthesis of 5‐/8‐Halogenated or Ethynylated Lipophilic Nucleobases as Potential Synthetic Intermediates for Supramolec­ular Chemistry

“…The yields of U2Alk10 and U2Alk6 were not very satisfactory, although they are in the same range of those reported on similar alkylation reactions with uridine derivatives. [18] One of the reasons for these relatively low yields is the additional formation of N-3-substituted products and the corresponding dialkylated products, identified by 1 H NMR and MS, which compete with alkylation at N-1. Finally, 1-Alkyl-5-iodouracils were then converted to the corresponding 5-ethynyl derivatives via cross-coupling reaction with TMSA.…”

Tuning the hydrogen-bonding strength in 2,6-bis(cycloalkylcarbonylamino)pyridine assemblies by variable flexibility. Association constants measured by hydrogen-bonded vs. non-hydrogen-bonded protons

“…One of the most frequently used methods is the 1 H NMR titration. This is due to the very high sensitivity of chemical shifts of hydrogen-bonded nuclei (usually protons of OH and/or NH groups) to concentration, water content [6] and quite often to many coexisting hydrogen-bonding processes [7][8][9]. Thus monitoring several nuclei is the method of choice to improve the reliability of obtained results.…”

“…Triple hydrogen-bonded associates are met in many structures as in DNA [14,15], amides [16,17], artificial sensors [18][19][20][21][22], materials [23], non-covalent polymers [4,[24][25][26][27][28] and in recently observed associates of orotic acid [29,30]. Triple hydrogen-bonded assemblies carrying 2,6-diaminopyridine DAD-hydrogen bonding moiety were studied by some groups with the use of various methods [4,6,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] and also by us [48,49]. We noticed that the use of NH and CH proton shifts as probes in Previously [48] we confirmed results from other group [50] reporting that the 2,6-bis(acylamino)pyridine do not dimerize.…”