Utilization of Self‐Sorting Processes To Generate Dynamic Combinatorial Libraries with New Network Topologies

Abstract

The synthesis of water-soluble, organometallic macrocycles is described. They were obtained by self-assembly in reactions of the half-sandwich complexes [[Ru(C6H5Me)Cl2]2], [[Ru(p-cymene)Cl2]2], [[Rh(Cp)Cl2]2], and [[Ir(Cp*)Cl2]2] with the ligand 5-dimethylaminomethyl-3-hydroxy-2-methyl-4-(1H)-pyridone in buffered aqueous solution at pH 8. The structure of the Ru-(p-cymene) complex was determined by single-crystal X-ray crystallography. Upon mixing, these complexes undergo scrambling reactions to give dynamic combinatorial libraries. In combination with structurally related complexes based on amino-methylated 3-hydroxy-2-(1H)-pyridone ligands, an exchange of metal fragments but no mixing of ligands was observed. This self-sorting behavior was used to construct dynamic combinatorial libraries of macrocycles, in which two four-component sub-libraries are connected by two common building blocks. This type of network topology influences the adaptive behavior of the library as demonstrated in selection experiments with lithium ions as the target.

Disulfides, Imines, and Metal Coordination within a Single System: Interplay between Three Dynamic Equilibria

“…[7,9] Herein we report a system in which three distinct kinds of linkages, disulfide (S À S), imine (C=N) and coordinative (N!metal) were shown to be capable of simultaneous dynamic exchange. [10] Equilibria between the homo-and hetero-disulfide subcomponents of this system could be perturbed by more than two orders of magnitude by changes at the coordinative and imine linkages. None of these dynamic exchange processes interfered chemically with the others, marking the three as mutually compatible and "orthogonal", in similar fashion to systems investigated in the groups of Miller, [11] Lehn, [12] and Meijer.…”

“…[13] This study thus represents the first report on the interplay between three separate reversible chemistries, allowing a novel entry into the emerging area of systems chemistry. [10,14] Abstract: We report a system in which three distinct dynamic linkages, disulfide (S À S), imine (C=N), and coordinative (N!metal) bonds were shown to be capable of simultaneous reversible exchange. The "disulfide layer" of the system under study consists of two homo-disulfides, bis(4-aminophenyl) disulfide 1 and bis(4-methoxyphenyl) disulfide 2 that equilibrate in the presence of catalytic amount of triethylamine to favor the formation of a hetero-disulfide product, 4-aminophenyl-4'-methoxyphenyl disulfide 3.…”

Deconvolution of a multi-component interaction network using systems chemistry

“…First, similar to the molecular networks operating inside living cells, our designed experimental system are based on an intricate web of molecular recognition events. The fact that both experiments and simulations show that selfsorting is a relatively common behavior (20%) suggests that the use of self-sorting systems -particularly ones with segregated network topologies [51] -as the basis for the further development of non-natural functional complex systems is justified. One strategy that Nature uses to control the connectivity of its networks is compartmentalization.…”

Dynamic Combinatorial Chemistry: The Unexpected Choice of Receptors by Guest Molecules

“…These approaches have been successfully applied to obtain a variety of receptors to bind different classes of guests, such as Li + and ammonium ions, and even a neurotransmitter. [5][6][7] The elegance and power of the concept of amplification (and thus identification) of the best receptor was an issue of recent debate. Computer simulations [8] and thermodynamic/statistical analysis, supported by experimental data, [8a, 9] on dynamic combinatorial libraries (DCLs) of the types shown in Figure 1 indicated that certainly not in all situations does the best receptor need to be amplified by the addition of the target.…”