Scope and Limitations of Supramolecular Autoregulation

Abstract

Recently, our group has reported on the ureidopyrimidinone (UPy) induced buffering of 2,7-diamido-1,8-naphthyridine (NaPy) and used this phenomenon to regulate the catalysis of the Michael addition of 2,4-pentanedione to trans-β-nitrostyrene. We now show that the observed catalytic activity of NaPy is the result of a strong synergy between NaPy and trace amounts of K 2 CO 3 , resulting in a more than 100-fold increase in reaction rate compared to the two compounds separately. By keeping the concentration of K 2 CO 3 , as well as NaPy, constant, an improved regulation of the catalytic activity is achieved. We show that the catalytic activity can be precisely regulated in a noncovalent manner via the addition of the UPy motif. Finally, different salts and Michael substrates are screened to assess the selectivity of this catalytic couple and to provide a platform for future research in molecular buffering, regulation, and chemical networks.

Supramolecular interactions between catalytic species allow rational control over reaction kinetics

“…In good agreement with our previous work on a structurally similar NaPy,26 both NaPy 1 and K 2 CO 3 were found to be required for efficient catalysis between Mal ref 3 and Pent ref 4 (Fig. 2a and b).…”

“…1a). 26 It was shown that this reaction displays bimolecular reaction kinetics and that the overall reaction rate can be regulated by inhibition using the NaPy complementary ureidopyrimidinone (UPy) motif 26. We also showed that a fixed ratio of NaPy and ditopic UPy can be diluted while buffering the concentration of catalytically active free NaPy, thereby desensitizing the Michael additions' rate to dilution 24–27…”

“…Because such supramolecular catalysts are typically held together by relatively weak hydrogen bonds, their compositions – and thereby their activities and selectivities – are more open to gradual and dynamic regulation ( e.g. , by inhibition through the addition of a competing binding motif) 23–26. Furthermore, the dynamic nature of supramolecular catalysts enhances their susceptibility to interact with other reaction components, which facilitates feedback mechanisms and communication between otherwise distinct reactions.…”

Supramolecular Buffering by Ring–Chain Competition

“…Subsequent investigations have shown that the catalytic activity of NaPy 2 is more complex than previously reported and that it most probably acts as a buffered phase transfer catalyst. 16 Here, we focus on the observation that the concentration of free NaPy (C NaPyfree ) can be buffered over a large concentration range when the concentrations of both NaPy (C NaPy-total ) and ditopic UPy (C ditopic UPy ) are increased simultaneously in a 1:1 ratio. The molecular mechanism by which component buffering occurs is described by a two-component equilibrium model that describes competition between cyclization and chain growth of a ditopic molecule and end-capping by a monotopic component.…”

Model-driven engineering of supramolecular buffering by multivalency

“…Recently, our group reported on a two-component supramolecular buffering system based on a self-associating divalent ureidopyrimidinone (UPy) molecule and a monovalent naphthyridine (NaPy) molecule that undergoes dimerization with UPy chain ends ( 29 , 30 ) ( Fig. 1 A ).…”