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.

Chemical double mutant cycles have been used in conjunction with new H-bonding motifs for the quantification of chelate cooperativity in multiply H-bonded complexes. The double mutant cycle approach specifically deals with the effects of substituents, secondary interactions, and allosteric cooperativity on the free energy contributions from individual H-bond sites and allows dissection of the free energy contribution due to chelate cooperativity associated with the formation of intramolecular noncovalent interactions. Two different doubly H-bonded motifs were investigated in carbon tetrachloride, chloroform, 1,1,2,2-tetrachloroethane, and cyclohexane, and the results were similar in all cases, with effective molarities of 3-33 M for formation of intramolecular H-bonds. This corresponds to a free energy penalty of 3-9 kJ mol -1 for formation of a bimolecular complex in solution, which is consistent with previous estimates of 6 kJ mol -1 . This result can be used in conjunction with the H-bond parameters, R and β, to make a reasonable estimate of the stability constant for formation of a multiply H-bonded complex between two perfectly complementary partners, or to place an upper limit on the stability constant expected for a less complementary system.

Cooperativity is a general feature of intermolecular interactions in biomolecular systems, but there are many different facets of the phenomenon that are not well understood. Positive cooperativity stabilizes a system as progressively more interactions are added, and the origin of the beneficial free energy may be entropic or enthalpic in origin. An ''enthalpic chelate effect'' has been proposed to operate through structural tightening that improves all of the functional group interactions in a complex, when it is more strongly bound. Here, we present direct calorimetric evidence that no such enthalpic effects exist in the cooperative assembly of supramolecular ladder complexes composed of metalloporphyrin oligomers coordinated to bipyridine ligands. The enthalpic contributions of the individual coordination interactions are 35 kJ⅐mol ؊1 and constant over a range of free energies of self-assembly of ؊35 to ؊111 kJ⅐mol ؊1 . In rigid well defined systems of this type, the enthalpies of individual interactions are additive, and no enthalpic cooperative effects are apparent. The implication is that in more flexible, less well defined systems such as biomolecular assemblies, the enthalpy contributions available from specific functional group interactions are well defined and constant parameters.cooperative phenomena ͉ enthalpy-entropy compensation ͉ supramolecular chemistry ͉ weak interactions C ooperativity is of fundamental importance for understanding molecular recognition processes in chemistry and biology. If two molecules bearing one complementary binding site interact to give a complex of stability ⌬G, then two molecules bearing n complementary binding sites generally interact to give a complex with stability larger than n⌬G. This phenomenon is known as positive cooperativity. The factors that are responsible for cooperative intermolecular interactions can be divided in two groups: entropic factors relating to the loss of motion of the molecules and enthalpic factors due to the reinforcement of the bonds. The simplest formulation of the entropic factors is the chelate effect: an interaction working in isolation must pay the entropic cost of bringing two molecules together, but when multiple interactions are made, this price is paid only once, so additional interactions make a bigger contribution to stability than the first one (1-3). The entropic term also includes any change in the internal rotations and vibrations of the molecules. Enthalpic contributions to cooperative binding can come from secondary functional group interactions, conformational changes, or polarization of the interacting groups. However, enthalpy and entropy are intimately related, so an increase in the enthalpic driving force for complexation has a direct impact on the mobility of the molecules involved in the complex. For weak intermolecular interactions, the entropy lost on formation of the first interaction is only a fraction of the total possible loss, because the molecules retain a good deal of independent mobility. As the number of ...

We describe the thermodynamic characterization of the assembly process of a covalently connected trimeric Zn porphyrin induced by coordination to a bispyridyl functionalized perylene bisimide . The perylene bisimide ligands act as pillars via two axial coordination bonds with the porphyrinic Zn(ii) ions fixing the planes of the porphyrin units in a nearly co-facial orientation and inducing the formation of trigonal prism-like structures. The fully assembled (2).(3) aggregate and the partially assembled one, (2).(2), in which only two zinc porphyrin sites of trimeric are axially coordinated to , are present in solution in equilibrium with freely diffusing species and . The strong quenching observed in the mixture for the luminescence of the components and is ascribed to an efficient photoinduced electron transfer from the Zn porphyrin units of to coordinated occurring upon excitation of both components within the assemblies. In the formed assemblies, the Zn porphyrin units of the trimer behave independently. Thus, the porphyrin units that are not coordinated with in the partially assembled complex, (2).(2), display the same photophysical behaviour registered for freely diffusing . The rate of charge separation within the cage is nearly independent on the polarity of the solvent (ca. 10(10) s(-1)) whereas the charge recombination process, leading to the ground state, has a lifetime of 110 ps in dichloromethane and ca. 6 ns in toluene, in agreement with a Marcus inverted behaviour.