Isothermal calorimetric titrations on charge-assisted halogen bonds: role of entropy, counterions, solvent, and temperature.

We have conducted isothermal calorimetric titrations to investigate the halogen-bond strength of cationic bidentate halogen-bond donors toward halides, using bis(iodoimidazolium) compounds as probes. These data are intended to aid the rational design of halogen-bond donors as well as the development of halogen-bond-based applications in solution. In all cases examined, the entropic contribution to the overall free energy of binding was found to be very important.

Nanomechanical recognition of N-methylammonium salts.

Turning molecular recognition into an effective mechanical response is critical for many applications ranging from molecular motors and responsive materials to sensors. Herein, we demonstrate how the energy of the molecular recognition between a supramolecular host and small alkylammonium salts can be harnessed to perform a nanomechanical task in a univocal way. Nanomechanical Si microcantilevers (MCs) functionalized by a film of tetra-phosphonate cavitands were employed to screen as guests the compounds of the butylammonium chloride series 1-4, which comprises a range of low molecular weight (LMW) molecules (molecular mass < 150 Da) that differ from each other by one or a few N-methyl groups (molecular mass 15 Da).

Hosting anions. The energetic perspective.

Hosting anions addresses the widely spread molecular recognition event of negatively charged species by dedicated organic compounds in condensed phases at equilibrium. The experimentally accessible energetic features comprise the entire system including the solvent, any buffers, background electrolytes or other components introduced for e.g.

Calix[4]pyrrole-based anion transporters with tuneable transport properties.

Three new bis-1,2,3-triazole strapped calix[4]pyrroles have been prepared via'click' chemistry and their anion complexation and lipid bilayer transport properties studied by a combination of single crystal X-ray diffraction studies, (1)H NMR titration techniques, isothermal titration calorimetry and lipid bilayer anion transport studies in POPC vesicles. Bilayer transport efficiency for transmembrane chloride transport was found to directly depend on the length of the alkyl chain present in the bis-triazole strap.

1,2,3-triazole-strapped calix[4]pyrrole: a new membrane transporter for chloride.

A new triazole-strapped calix[4]pyrrole synthesised via'click' chemistry shows high affinity for chloride and lipid bilayer chloride transport properties.

Cooperative binding of calix[4]pyrrole-anion complexes and alkylammonium cations in halogenated solvents.

Calix[4]pyrrole-chloride interactions are affected not only by the choice of countercation in halogenated solvents, but show a specific dependence on the way in which these cations are bound within the electron rich, bowl-like calix[4]pyrrole cavity formed upon chloride anion complexation. In dichloromethane, the affinities of simple meso-octamethylcalix[4]pyrrole (1) for methyl-, ethyl-, and n-butylammonium chlorides are on the order of 10(5), 10(4), and 10(2) M(-1), respectively, as determined from isothermal titration calorimetry (ITC) analyses. These cation-dependent anion affinity effects, while clearly evident, are less pronounced in other halogenated solvents, such as 1,2-dichloroethane.

Addressing association entropy by reconstructing guanidinium anchor groups for anion binding: design, synthesis, and host-guest binding studies in polar and protic solutions.

The bicyclic hexahydropyrimidino[1,2a]pyrimidine cationic scaffold has a well-known capacity to bind a variety of oxoanions (phosphates, carboxylates, squarates, phosphinates). Based on this feature, the parent host was supplemented with sec-carboxamido substituents to generate compounds 1-3 in an effort to improve the anion-binding affinity and selectivity and to learn about the role and magnitude of entropic factors. Bicyclic guanidinium compounds were prepared by a convergent strategy via the corresponding tetraester 22 followed by catalytic amidation.

A novel synthesis of chiral guanidinium receptors and their use in unfolding the energetics of enantiorecognition of chiral carboxylates.

A novel synthetic route to the versatile chiral bicyclic guanidinium building block is described making use of l-methionine as a starting material from the natural chiral pool. Furthermore, the synthetic elaboration of this building block is shown in the construction of macrocyclic and open chain hosts, respectively. The host design employs urea functions as the connecting units and supplementary anchor groups for the complexation of anions.

Calix[4]pyrrole as a chloride anion receptor: solvent and countercation effects.

The interaction of calixpyrrole with several chloride salts has been studied in the solid state by X-ray crystallography as well as in solution by isothermal titration calorimetry (ITC) and (1)H NMR spectroscopic titrations. The titration results in dimethylsulfoxide, acetonitrile, nitromethane, 1,2-dichloroethane, and dichloromethane, carried out using various chloride salts, specifically tetraethylammonium (TEA), tetrapropylammonium (TPA), tetrabutylammonium (TBA), tetraethylphosphonium (TEP), tetrabutylphosphonium (TBP), and tetraphenylphosphonium (TPhP), showed no dependence on method of measurement. The resulting affinity constants (K(a)), on the other hand, were found to be highly dependent on the choice of solvent with K(a)'s ranging from 10(2)-10(5) M(-1) being recorded in the test solvents used for this study.

Judging on host-guest binding mode uniqueness: association entropy as an indicator in enantioselection.

[reaction: see text] Supramolecular enantiodifferentiation was studied by isothermal titration calorimetry in an effort to address the order-disorder distinction in the diastereomeric complexes formed from a chiral macrocyclic host and enantiomeric carboxylates. As a result, the association entropy component TDeltaS emerged as an indicator in the enantioselection of tartrate 14 and aspartate 15 by the macrocycle 13 containing two guanidinium anchor groups connected to each other by four urea units. The parent monotopic guanidinium compounds 1 or 2 did not show any enantioselection for chiral carboxylates.

Surprises in the design of anion receptors: calorimetry prevents false reasoning.

Supplementing bicyclic guanidinium anion receptors with four sec-carboxamido groups leads to enhanced affinity for oxoanions, however, for a different reason than originally planned. Calorimetric analysis reveals that better binding is due to higher association entropies rather than more negative enthalpies. Thus, molecular design following geometric and functional complementarity principles may misguide supramolecular constructions aimed at a unique host-guest binding mode, as required, e.

Probing binding-mode diversity in guanidinium-oxoanion host-guest systems.

An attempt to experimentally estimate the role of binding-mode diversity (structural fuzziness) on the molecular recognition seen in the prominent guanidinium-oxoanion host-guest pair is described. The global heat response as measured by isothermal titration calorimetry in acetonitrile, which was obtained from the interaction of five different but structurally closely related guanidinium hosts with three rigid phosphinate guests of decreasing accessibility of their binding sites, is correlated to provide a trend analysis. All host-guest associations of 1:1 stoichiometry in this series are strongly enthalpy-driven.

A novel method for the N-terminal modification of native proteins.

The formation of structurally defined bioconjugates of proteins hinges on their regioselective modification. Toward this goal a novel method is described here using the commercial IgA protease to attach a nonnatural peptidic moiety to the N-terminus of predisposed proteins by means of a kinetically controlled reverse proteolysis in water. The process requires an H-Ala-Pro N-terminal sequence and then furnishes a selectively modified conjugate under nondenaturing and nondestructive conditions in acceptable yield.

The anatomy of the energetics of molecular recognition by calorimetry: chiral discrimination of camphor by alpha-cyclodextrin.

The molecular recognition of both camphor enantiomers 2 with the chiral alpha-cyclodextrin (alpha-CD) 1 in water and D(2)O was examined by calorimetry. On the basis of statistically supported determinations the thermodynamics of 2:1 host-guest binding and chiral discrimination was evaluated. The energetic signature strongly supports hydrophobic interaction as the dominant driving force for camphor encapsulation by alpha-CD in water.

Surprises in the energetics of host-guest anion binding to calix[4]pyrrole.

Contrary to common expectation, calorimetric measurements do not corroborate the preference of calix[4]pyrrole for fluoride over chloride in acetonitrile solution.

Anion-controlled assembly of porphyrin-bicyclic guanidine conjugates.

[reaction: see text] Cationic porphyrins 1-3 bearing one, two, and four bicyclic guanidines form highly ordered chiral assemblies in aqueous solutions. The chirality is controlled by the type of the anionic counterpart and results from a spontaneous process. The chiral assemblies of 1-3 relate structurally to the complexes of achiral porphyrins with helical DNA.

The Binding of Sulfate Anions by Guanidinium Receptors is Entropy-Driven.

Clear trends in the molecular recognition of guest species by artificial hosts in solution are often observed by intrinsic enthalpy-entropy compensation, which requires the dissection of these free-energy components. Contrary to common belief, it is not the enthalpic electrostatic attraction that makes guanidinium hosts such as 1 strong binders for sulfate anions. Isothermal titration calorimetry has now allowed this molecular recognition to be characterized as an entropy-driven association.

Bioconjugation of Peptides by Palladium-Catalyzed C-C Cross-Coupling in Water.

The abiotic, regioselective conjugation of peptides and proteins with non-proteinogenic structural elements requires mild and fast coupling reactions which are compatible with an aqueous reaction medium and orthogonal in their reactivity with all other functional groups in the protein. Sonogashira coupling with a palladium-guanidinophosphane catalyst that is prepared in situ (see reaction on the right) complies with these demands.

Water Soluble Cationic Phosphine Ligands Containing m-Guanidinium Phenyl Moieties. Syntheses and Applications in Aqueous Heck Type Reactions.

Cationic phosphine ligands containing m-guanidinium phenyl substituents {Ph(3-n)P[C(6)H(4)-m-NHC(NH(2))(NMe(2))](n)}(n+) nCl(-) (n = 1-3) (17a-c) have been obtained by addition of dimethylcyanamide to the amino groups of tertiary (m-aminophenyl)phosphines in acidic medium. The tertiary (m-aminophenyl)phosphines Ph(3-n)P(C(6)H(4)-m-NH(2))(n) (4a-c) were prepared by reaction of (3-[N,N-bis(trimethylsilyl)amino]phenyl)magnesium chloride (1) with chlorophosphines Ph(3-n)PCl(n) followed by deprotection of the bis(trimethylsilyl)amino groups with methanol. Using a similar protected group synthesis as above, the secondary (m-aminophenyl)phosphine Ph(H)PC(6)H(4)-m-NH(2) (7) could be prepared as well.