Chemical Double Mutant Cycles for the Quantification of Cooperativity in H-Bonded Complexes

Abstract

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.

Nanorings with copper(ii) and zinc(ii) centers: forcing copper porphyrins to bind axial ligands in heterometallated oligomers

“…41,56 This approach allows one to disentangle the free energy contribution due to chelate cooperativity associated with the formation of intramolecular non-covalent interactions. We envisioned that we could utilize the cooperative binding effect of the four zinc porphyrins in P5 Cu to force the copper center to interact with the template and determine its contribution to the binding strength.…”

“…The DMC approach overcomes these problems by cancelling the secondary free energy effects of the mutations in a pairwise fashion in the thermodynamic cycle. 41 The cycle is completed by probing the stability of complex D ( P5 2H ·T4 ), in which both the copper center and the central binding leg are removed.…”

“…Here we demonstrate that heterometallated linear porphyrin oligomers can be used to measure the weak interaction of a copper center with axial nitrogen ligands, without requiring high concentrations of the pyridine ligand, by utilizing the cooperative effect of neighboring zinc centers in a chemical double-mutant cycle. 41 …”

Oxidation effect on double H-bonded imidazole–adenine–imidazole trimer

“…The C 6 -N 6 bond reduces to 1.335 Å as compared with that in IAI1 and IAI2 due to the cooperativity of N 6 -H 11 ÁÁÁN and N 6 -H 12 ÁÁÁN H bonds. The H-bond cooperativity has been discussed experimentally and theoretically [35][36][37][38][39].…”

Cooperative Binding of Divalent Diamides by N‐Alkyl Ammonium Resorcinarene Chlorides

“…Cooperativity arises from the interplay of two or more interactions behaving differently from expectationsbased on the properties of the individual interactions acting in isolation. [2][3][4] This phenomenoni s usually observed in multivalent processes in which the coupling of interactions can lead to positive or negative cooperativity,d epending on whether one process favors or disfavors another.C ooperativity is vital in systems chemistryb ecause it can lead to collective properties that are absent in the individual molecular components, and this phenomenon constitutes one of the most important properties of molecular systems in biology. [2,3,5] Positive cooperativity occurs when the binding of one substrate leads to highera ffinity of subsequent substrates, and is ac ommon phenomenon in substrate recognition by enzymes.…”