AAA−DDD Triple Hydrogen Bond Complexes

Abstract

Experiment and theory both suggest that the AAA-DDD pattern of hydrogen bond acceptors (A) and donors (D) is the arrangement of three contiguous hydrogen bonding centers that results in the strongest association between two species. Murray and Zimmerman prepared the first example of such a system (complex 3*2) and determined the lower limit of its association constant (K(a)) in CDCl(3) to be 10(5) M(-1) by (1)H NMR spectroscopy (Murray, T. J. and Zimmerman, S. C. J. Am. Chem. Soc. 1992, 114, 4010-4011). The first cationic AAA-DDD pair (3*4(+)) was described by Bell and Anslyn (Bell, D. A. and Anslyn, E. A. Tetrahedron 1995, 51, 7161-7172), with a K(a) > 5 x 10(5) M(-1) in CH(2)Cl(2) as determined by UV-vis spectroscopy. We were recently able to quantify the strength of a neutral AAA-DDD arrangement using a more chemically stable AAA-DDD system, 6*2, which has an association constant of 2 x 10(7) M(-1) in CH(2)Cl(2) (Djurdjevic, S., Leigh, D. A., McNab, H., Parsons, S., Teobaldi, G. and Zerbetto, F. J. Am. Chem. Soc. 2007, 129, 476-477). Here we report on further AA(A) and DDD partners, together with the first precise measurement of the association constant of a cationic AAA-DDD species. Complex 6*10(+)[B(3,5-(CF(3))(2)C(6)H(3))(4)(-)] has a K(a) = 3 x 10(10) M(-1) at RT in CH(2)Cl(2), by far the most strongly bound triple hydrogen bonded system measured to date. The X-ray crystal structure of 6*10(+) with a BPh(4)(-) counteranion shows a planar array of three short (NH...N distances 1.95-2.15 A), parallel (but staggered rather than strictly linear; N-H...N angles 165.4-168.8 degrees), primary hydrogen bonds. These are apparently reinforced, as theory predicts, by close electrostatic interactions (NH-*-N distances 2.78-3.29 A) between each proton and the acceptor atoms of the adjacent primary hydrogen bonds.

A Review of Polymeric Refabrication Techniques to Modify Polymer Properties for Biomedical and Drug Delivery Applications

“…Such polymers that are capable of self-assembling into contemporaneously integrated complexes considering multiple hydrogen bonds possess strength, orientation, and specificity (91)(92)(93)(94). As the number of hydrogen bonds increases in a given complex, the magnitude of favorable properties could possibly increase proportionally (93,95). One such example is the polymer network formed from the polymerization of acrylic acid in aqueous sodium hydroxide with acrylamide which occurs via hydrogen bonding (10).…”

“…The triple hydrogen bonding system exhibits stronger networks over the double hydrogen bonding systems, correspondingly offering more possibilities for the formation of new polymers (90,93,95). However, the greater the number of possible hydrogen bonds that can be formed, the greater the influence on complex stability since this relies on the arrangement of donor and acceptor groups (90,95).…”

“…However, the greater the number of possible hydrogen bonds that can be formed, the greater the influence on complex stability since this relies on the arrangement of donor and acceptor groups (90,95). In the case where two donor or two acceptor groups are situated adjacent to one another (even if on different molecules), there is approximately 7 kJ/mol causing secondary electrostatic repulsion (92)(93)(94)(95).…”

“…However, the greater the number of possible hydrogen bonds that can be formed, the greater the influence on complex stability since this relies on the arrangement of donor and acceptor groups (90,95). In the case where two donor or two acceptor groups are situated adjacent to one another (even if on different molecules), there is approximately 7 kJ/mol causing secondary electrostatic repulsion (92)(93)(94)(95). This interaction causes a destabilizing effect consequently effectuating variances in the dimerization strength and subsequently variances in the complexation strength of triple HBCs (92)(93)(94)(95).…”

“…In the case where two donor or two acceptor groups are situated adjacent to one another (even if on different molecules), there is approximately 7 kJ/mol causing secondary electrostatic repulsion (92)(93)(94)(95). This interaction causes a destabilizing effect consequently effectuating variances in the dimerization strength and subsequently variances in the complexation strength of triple HBCs (92)(93)(94)(95). A worse situation arises when the groups accountable for the secondary interaction do not participate in hydrogen bonding.…”