Role of the Symmetry of Multipoint Hydrogen Bonding on Chelate Cooperativity in Supramolecular Macrocyclization Processes

Abstract

Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: Copyright: © 2016 Wiley VCH VerlagEl acceso a la versión del editor puede requerir la suscripción del recurso Access to the published version may require subscription The Role of Multipoint Hydrogen-bond Symmetry on Chelate Cooperativity in Supramolecular MacrocyclizationsCarlos Montoro-García, [a] Jorge Camacho-García, [a] Ana M. López-Pérez, [a] María J. Mayoral, [a] Nerea Bilbao, [a] and David González-Rodríguez [a] *Abstract: Here, we analyze the intrinsic chelate effect that multipoint H-bonding patterns exert in the overall energy of dinucleoside cyclic systems. Our results indicate that the magnitude of EM is regulated by the symmetry of the H-bonding pattern, which is reduced by about 3 orders of magnitude when going from the unsymmetric ADD-DAA or DDA-AAD patterns to the symmetric DAD-ADA pattern.The supramolecular synthesis [1] of complex nanostructures with a precision analogous to that found in the natural world requires not only an understanding of the noncovalent interactions involved, [2] but also of cooperative and multivalent phenomena that may arise between the individual constituents, since the control of structure and monodispersity depends largely on this issue. [3] A molecule with more than one binding site may assemble into linear (open) or cyclic (closed) structures. Although the size of linear oligomers can be sometimes limited within a certain range, the supramolecular product is commonly a statistical distribution of chain lengths.[4]Therefore, the synthesis of discrete supramolecular structures has normally been focused on closed (multi)macrocyclic systems, where size and structure are dictated by the geometric requirements of the monomer and the binding interaction. [5] The effect that causes the quantitative formation of a particular ring-closed species is defined as chelate cooperativity, and stems from the fact that an intramolecular interaction is favored over an intermolecular one, providing a series of conditions of enthalpic and entropic origin are met. [3] The increased in stability when comparing a linear and a cyclic oligomer of a certain length is given by the product K inter ·EM, where K inter is the intermolecular binding constant and considers the additional association to form the cycle, whereas EM, the key parameter quantifying chelate cooperativity, stands for effective molarity and takes into account that this last binding event is intramolecular (EM = K intra /K inter ). [6] In this context, multipoint H-bonding motifs, constituted by an array of vicinal H-bonding donor (D) and acceptor (A) groups, arise as a relevant noncovalent interaction increasingly used to produce not only discrete cyclic assemblies, but also supramolecular polymers and functional materials.[7] A relevant example is represented by the nucleobases [8] and DNA itself, constituted by combinations of unsymmetric ADD-DAA guaninecytosine and symmetric DA-AD adenine...

Impact of Conformational Effects on the Ring–Chain Equilibrium of Hydrogen‐Bonded Dinucleosides

“…We previously demonstrated that GC1 cyclic tetramers ( c GC1 4 ) are formed quantitatively in solvents of moderate polarity due to the strong chelate effects attained . More recent work in our group has focused on evaluating the dependence of the length of the phenylene‐ethynylene spacer that connects the two bases ( n in Figure b) on chelate cooperativity . Different monomers were prepared in which n varied from 1 to 5.…”

Mechanical measurement of hydrogen bonded host–guest systems under non-equilibrium, near-physiological conditions

“…Hydrogen bonds are arguably the most prominent of noncovalent interactions, as the very foundations of life as we know it depend crucially on H-bonding. 1 From a synthetic point of view, a wealth of host–guest systems, 2 supramolecular polymers, 3 and molecular machines 4 based on H-bonding has been described. 5 Unsurprisingly, measuring and understanding H-bonds has been the subject of intensive research efforts, and it still busies the scientific community.…”

How Large Can We Build a Cyclic Assembly? Impact of Ring Size on Chelate Cooperativity in Noncovalent Macrocyclizations

“…[b] Determined as EM = K T / K ref 4 using the data calculated from the NMR dilution in [D 6 ]DMF (Figure S2B), NMR dilution in [D 8 ]THF (Figure S2 A), NMR competition experiments with C in CDCl 3 (Figure S3 B), respectively. [c] EM values ranging between 2.2×10 2 –3.6×10 2 m (DMF), 1.8×10 2 –7.3×10 2 m (THF), and 8.1×10 2 –9.1×10 2 m (CHCl 3 ) were previously determined by us for GC1 –…”

“…We recently reported an example of a dinucleoside monomer ( GC1 ; Figure b) based on a π‐conjugated p ‐diethynylbenzene unit substituted with complementary nucleobases at the edges: guanine (G) and cytosine (C), which have bulky lipophilic ribose groups to afford solubility and prevent stacking interactions. This rigid and linear structure, together with the 90° angle provided by Watson–Crick pairing, resulted in the formation of unstrained square‐shaped H‐bonded cyclic tetramers ( c GC1 4 ), which displayed remarkable thermodynamic and kinetic stabilities ascribed to the large EM values attained (10 2 –10 3 m ) ,. Further investigations allowed us to conclude that such record chelate cooperativities stem from: 1) a rigid predisposed monomer geometry, and 2) an unsymmetric (i.e.…”

“…The results obtained in these experiments, which are displayed and detailed in the Supporting Information, led to the conclusion that the longer the central block connecting the bases, the lower the thermodynamic stability of the cyclic assembly. Table compiles the EM values that could be calculated for GC1 – GC5 in DMF, THF, and CHCl 3 in the different dilution and competition experiments performed (see our previous work– and the Supporting Information for further details). As the macrocycle becomes larger, the magnitude of EM in THF and CHCl 3 undergoes a drastic decrease that encompasses 5 orders of magnitude, from over 10 2 m for GC1 to 10 −3 m for GC5 .…”