A general treatment of macrocyclization reactions occurring under thermodynamic control is presented. The fundamental quantities on which the treatment is based are the effective molarities of the cyclic oligomers and the equilibrium constant for the intermolecular model reaction between monofunctional reactants (Kinter). Four typical cases have been considered, namely, addition and condensation of a monomer of the type A-B, addition of A-A, and addition of A-A + B-B. A critical comparison with the classical theory of Jacobson and Stockmayer is presented.It is shown that the phenomenon characterized by the critical monomer concentration (cut-off point) is a limiting phenomenon which would occur only for infinitely large values of Kin,,,. The treatment has been successfully applied to the DOS/DTC-induced cyclooligomerization of /3-propiolactone in CDC13 solution that yields well-behaved ringchain equilibrates closely adhering to the theoretical model. Best fit of the experimental product distributions to the general equations gave the equilibrium constant (Kinter) of the intermolecular model reaction, as well as the effective molarities (EMi) for the cyclic oligomers from trimer to octamer. The EMi values decrease in proportion of the -2.5 power of the oligomerization degree, thus providing a strong indication that the oligomeric polylactones are essentially strainless. The extremely low value of Kin,,, (2.5) is responsible for the absence of a cut-off point, which is usually present in ring-chain polymeric equilibrates.

A new tripodal receptor for the recognition of monosaccharides is described. The prototypical host 1 features a 1,3,5-substituted 2,4,6-triethylbenzene scaffold bearing three convergent H-bonding units. The binding ability of the t-octyl derivative 1a toward a set of octylglycosides of biologically relevant monosaccharides, including Glc, Gal, Man, and GlcNAc, was investigated by 1H NMR in CDCl3. A protocol for the correct evaluation of binding affinities was established, which can be generally applied for the recognition of monosaccharides by 1H NMR spectroscopy. A three-constant equilibrium model, including 1:1 and 2:1 host-guest association and dimerization of the receptor, was ascertained for the interaction of 1a with all the investigated glycosides. An affinity index, which we defined median binding concentration BC50 in analogy to the IC50 parameter, intended to address the general issue of comparing dimensionally heterogeneous binding data, and a limiting BC0(50)quantity describing intrinsic binding affinities were developed for evaluating the results. BC0(50) values for 1a range from 1 to 6 mM, indicating an intrinsic binding affinity in the millimolar range and a selectivity factor of 5 toward the investigated glycosides. The treatment has been extended to include any generic host-guest system involved in single or multiple binding equilibria.

The interaction of the lipophilic cyclophane 1 with several acetylcholine (ACh) and tetramethylammonium (TMA) salts has been investigated in deuteriochloroform to ascertain the influence of the counterion on the cation-pi interaction. Reliable association constants have been measured for 17 salts of commonly used anions; corresponding binding free energies -DeltaG degrees ranged from over 8 kJ mol(-1) down to the limit of detection. The dramatic dependence of the binding energy on the anion showed that the latter takes part in the process with a passive and adverse contribution, which inhibits cation binding even to complete suppression in unfavorable cases. Thermodynamic parameters for the association of 1 with TMA picrate demonstrate that binding is enthalpic in origin, showing a substantial enthalpy gain (DeltaH degrees = -16.7 kJ mol(-1)) and an adverse entropic contribution (DeltaS degrees = -27.9 J mol(-1) K(-1)). A correlation has been found between the "goodness" of anions as binding partners and the solubility of their salts. Conversion of the anion into a more charge-dispersed species, for example, conversion of chloride into dialkyltrichlorostannate, improves cation binding substantially, indicating that charge dispersion is a main factor determining the influence of the anion on the cation-pi interaction. DFT computational studies show that the variation of the binding free energy of TMA with the counterion is closely accounted for by the electrostatic potential (EP) of the ion pair: guest binding appears to respond to the cation's charge density exposed to the receptor, which is determined by the anion's charge density through a polarization mechanism. A value of -DeltaG degrees = 38.6 kJ mol(-1) has been extrapolated for the free energy of binding of TMA to 1 in chloroform but in the absence of a counterion. The transmission of electrostatic effects from the ion pair to the cation-pi interaction demonstrates that host-guest association is governed by Coulombic attraction, as long as factors (steric, entropic, solvation, etc.) other than pure electrostatics are not prevalent.

Pyrrolic and imino (3) or amino (4) H-bonding ligands were incorporated into a benzene-based tripodal scaffold to develop a new generation of receptors for molecular recognition of carbohydrates. Receptors 3 and 4 effectively bound a set of octylglycosides of biologically relevant monosaccharides, including glucose (Glc), galactose (Gal), mannose (Man), and N-acetyl-glucosamine (GlcNAc), showing micromolar affinities in CDCl3 and millimolar affinities in CD3CN by NMR titrations. Both receptors selectively recognized Glc among the investigated monosaccharides, with 3 generally less effective than 4 but showing selectivities for the all-equatorial beta-glycosides of Glc and GlcNAc among the largest reported for H-bonding synthetic receptors. Selectivities in CDCl3 spanned a range of nearly 250-fold for 3 and over 30-fold for 4. Affinities and selectivities were univocally assessed through the BC50 descriptor, for which a generalized treatment is described that extends the scope of the descriptor to include any two-reagent host-guest system featuring any number of binding constants. ITC titrations of betaGlc in acetonitrile evidenced, for both receptors, a strong enthalpic contribution to the binding interaction, suggesting multiple H bonding. Selectivity trends toward alphaGlc and betaGlc analogous to those obtained in solution were also observed in the gas phase for 3 and 4 by collision-induced dissociation experiments. From comparison with appropriate reference compounds, a substantial contribution to carbohydrate binding emerged for both the imino/amino and the pyrrolic H-bonding groups but not for the amidic group. This previously undocumented behavior, supported by crystallographic evidence, has been discussed in terms of geometric, functional, and coordinative complementarity between H-bonding groups and glycosidic hydroxyls and opens the way to a new designer strategy of H-bonding receptors for carbohydrates.