External and Internal Guest Binding of a Highly Charged Supramolecular Host in Water: Deconvoluting the Very Different Thermodynamics

Sgarlata, Carmelo; Mugridge, Jeffrey S.; Pluth, Michael D.; Tiedemann, Bryan E. F.; Zito, Valeria; Arena, Giuseppe; Raymond, Kenneth N.

doi:10.1021/ja9056739

Cited by 88 publications

(76 citation statements)

References 59 publications

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“…Based on this analysis, HDX proceeds up to 30× faster in B than A. We propose that encapsulated solvent provides a contribution to this difference (8-10 solvent molecules are expected to be encapsulated, based on thermogravimetric analysis) (42). It is also possible that HDX in the presence of excess G occurs simultaneously with guest exchange, as relevant guest self-exchange processes likely involve ligand distortion and occur 10-1,000× faster than the observed rates of HDX (43).…”

Section: Significancementioning

confidence: 91%

Protein-like proton exchange in a synthetic host cavity

Hart‐Cooper

Sgarlata

Perrin

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The mechanism of proton exchange in a metal-ligand enzyme active site mimic (compound 1) is described through amide hydrogendeuterium exchange kinetics. The type and ratio of cationic guest to host in solution affect the rate of isotope exchange, suggesting that the rate of exchange is driven by a host whose cavity is occupied by water. Rate constants for acid-, base-, and watermediated proton exchange vary by orders of magnitude depending on the guest, and differ by up to 200 million-fold relative to an alanine polypeptide. These results suggest that the unusual microenvironment of the cavity of 1 can dramatically alter the reactivity of associated water by magnitudes comparable to that of enzymes.W ater-mediated proton transfer in molecular cavities plays an essential role in the function of nature's remarkable metabolic machinery (1, 2). Of the broad diversity of enzymecatalyzed reactions, those involving transfer of hydrogen are ubiquitous and of high fundamental importance (3). For instance, ATP synthase employs an internal chain of water molecules to mediate proton transfer across an electrochemical gradient (4, 5). This process drives ATP synthesis, which allows organisms to broadly meet their basic energy needs. Recent studies of tunneling in enzymatic hydron transfer reactions have other far-reaching and broad implications, namely the importance of the dynamic enzyme motions in driving catalysis (6, 7).Of the methods used to study hydron transfer, kinetic studies of the mechanisms of amide hydrogen-deuterium exchange (HDX) have helped to elucidate the dynamic interactions between water and protein surfaces that are central to the unique capabilities of enzymes (8-13). Noncovalent interactions, such as electrostatic effects and hydrogen bonding, have also been shown to exert a significant influence on amide HDX rates. These properties are manifest in amide HDX rate constants that can vary by a factor of a billion for residues on the same protein (8). How these variations arise, and how such a property could be harnessed to drive enzyme-like reactivity, remain challenging questions.In a growing effort to emulate the efficacy of biological receptors and enzymes, studies of the preparative, guest-binding, and catalytic properties of synthetic assemblies have been pursued (14-21). Whereas guest encapsulation has been reported in a variety of media, association processes of organic guests are generally more thermodynamically favorable in water (22, 23). Central to these studies is the notion that the displacement of a high-energy water cluster from a receptor drives guest association, and in some cases, subsequent catalysis. However, despite the abundance of structural data documenting diverse water clusters encapsulated in various host cavities, mechanistic descriptions of the dynamic processes between water and host are rare (24-32).As part of the broader field of synthetic hosts previously mentioned, our group has developed a class of biologically inspired, anionic K 12 Ga 4 L 6 assemblies that exhibit cat...

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Section: Significancementioning

confidence: 91%

Protein-like proton exchange in a synthetic host cavity

Hart‐Cooper

Sgarlata

Perrin

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…[41,42] The DG8, DH8, and DS8 values for the formation of the main species for the two diastereoisomers are given in Table 3.…”

Section: à3mentioning

confidence: 99%

Intramolecular Weak Interactions in the Thermodynamic Stereoselectivity of Copper(II) Complexes with Carnosine–Trehalose Conjugates

Grasso

Arena

Bellia

et al. 2011

Chemistry A European J

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The interactions of metal ions with chiral molecules are of particular interest for relevant biochemical processes, as many of them are made possible only with a selected chirality of the stereocenters. In this work we report a study of the stereoselectivity of copper(II) complexes with D-trehalose-L-carnosine and D-trehalose-D-carnosine as a prototypical case of natural chirality selection. The interest in L-carnosine dipeptide is compounded by its antioxidant and antitumor properties, which are further enhanced when combined with D-trehalose. Potentiometric, calorimetric, and UV/circular dichroism (CD) spectroscopic measurements show that the copper(II) dimer of D-trehalose-L-carnosine is more stable than the D-trehalose-D-carnosine diastereoisomeric copper(II) dimer (log β(L)(22-2) - log β(D)(22-2) = 3.6). Free-energy calculations highlight that the cause of this different behavior lies with different intramolecular weak interactions between the diastereoisomers. The different pattern of hydrogen bonds and the different CH-π interactions between the π-electron-rich imidazole and the α-glucose rings are more favorable by 5 kcal mol(-1) in the L dimer.

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“…We have previously reported on the deconvolution of the very different driving forces for internal and external binding of Et 4 N + by host 1 in water. 24 This was achieved analyzing data obtained from three complementary techniques (NMR, ITC, and UV−vis) using suitable commercially available software packages.…”

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confidence: 99%

Untangling the Diverse Interior and Multiple Exterior Guest Interactions of a Supramolecular Host by the Simultaneous Analysis of Complementary Observables

Sgarlata

Raymond

2016

Anal. Chem.

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The entropic and enthalpic driving forces for encapsulation versus sequential exterior guest binding to the [Ga4L6](12-) supramolecular host in solution are very different, which significantly complicates the determination of these thermodynamic parameters. The simultaneous use of complementary techniques, such as NMR, UV-vis, and isothermal titration calorimetry, enables the disentanglement of such multiple host-guest interactions. Indeed, data collected by each technique measure different components of the host-guest equilibria and together provide a complete picture of the solution thermodynamics. Unfortunately, commercially available programs do not allow for global analysis of different physical observables. We thus resorted to a novel procedure for the simultaneous refinement of multiple parameters (ΔG°, ΔH°, and ΔS°) by treating different observables through a weighted nonlinear least-squares analysis of a constrained model. The refinement procedure is discussed for the multiple binding of the Et4N(+) guest, but it is broadly applicable to the deconvolution of other intricate host-guest equilibria.

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External and Internal Guest Binding of a Highly Charged Supramolecular Host in Water: Deconvoluting the Very Different Thermodynamics

Cited by 88 publications

References 59 publications

Protein-like proton exchange in a synthetic host cavity

Protein-like proton exchange in a synthetic host cavity

Intramolecular Weak Interactions in the Thermodynamic Stereoselectivity of Copper(II) Complexes with Carnosine–Trehalose Conjugates

Untangling the Diverse Interior and Multiple Exterior Guest Interactions of a Supramolecular Host by the Simultaneous Analysis of Complementary Observables

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