Dynamic Combinatorial Chemistry and Macrocyclization Equilibria

• Kinetic Trapping of an Out-of-Equilibrium Dynamic Library of Imines by Changing Solvent 

M. Valentini, G. Ercolani,  S. Di Stefano,  Chemistry a European  Journal 2024,  30, e2023038,  (HOT PAPER, cover feature)

When an Activated Carboxylic Acid (ACA) is employed to perturb a dynamic library of imines, the nature of the solvent has a crucial role in defining the non-equilibrium state of such library. A dissipative dynamic library in CD2Cl2, fully coupled with the decarboxylation of the ACA, or a kinetically trapped out-of-equilibrium dynamic library in CD3CN can be generated. 

Dissipative Dynamic Libraries (DDLs) and Dissipative Dynamic Combinatorial Chemistry (DDCC)

D. Del Giudice, E. Spatola, M. Valentini, G. Ercolani, S. Di Stefano,  ChemSystemsChem 2022, e202200023 (VERY IMPORTANT PAPER, cover feature, TOP 10% of highly downloaded from ChemSystemsChem during its first 12 months of publication). 

In this Concept the fundamental features of Dissipative Dynamic Libraries (DDLs) maintained out-of-equilibrium by the consumption of a fuel are described with particular emphasis on the factors that govern the composition of the libraries over the time. 

• Dissipative Dynamic Covalent Chemistry (DDCvC) Based on the Transimination Reaction 

D. Del Giudice, M. Valentini, G. Melchiorre, E. Spatola, S. Di Stefano,  Chemistry a European Journal, 2022, 28,  e202200685. (HOT PAPER)

Dissipative dynamic libraries (DDLs) of imines are generated by addition of 2-cyano-2-(4’-chloro)phenylpropanoic acid employed as a chemical fuel to equilibrated dynamic libraries (DLs). At the addition of the fuel the initial composition of the library dictated by the thermodynamic equilibrium is perturbed and a transient, temporal controllable, out of equilibrium state is obtained, which reverts to the initial equilibrium when the fuel is exhausted. 

• • The canonical behavior of the entropic component of thermodynamic effective molarity. An attempt at unifying covalent and noncovalent cyclizations. 

S. Di Stefano, L. Mandolini, Physical Chemistry Chemical Physics, 2019, 21, 955-987 (HOT ARTICLE 2018 and 2019).

• Formation of Imidazo[1,5–a]pyridine Derivatives Due to the Action of Fe2+ on Dynamic Libraries of Imines 

S. Albano, G. Olivo, L. Mandolini, C. Massera, F. Ugozzoli, S. Di Stefano, Journal of Organic Chemistry 2017, 82, 3820−3825.

• Statistical Ring Catenation under Thermodynamic Control: Should the Jacobson−Stockmayer Cyclization Theory Take into Account Catenane Formation?

S. Di Stefano, G. Ercolani, Journal of Physical Chemistry B 2017, 112, 649–656.

• •  Equilibrium Effective Molarity as a Key Concept in Ring-Chain Equilibria, Dynamic Combinatorial Chemistry, Cooperativity, and Self-Assembly

S. Di Stefano, G. Ercolani, Advances in Physical Organic Chemistry 2016, 50, 1–76.

• •  Ring–opening Metathesis Polymerization of a Diolefinic [2]–Catenane–copper(I) Complex: An Easy Route to Polycatenanes

J. A. Berrocal, L. M. Pitet, M. M. L. Nieuwenhuizen, L. Mandolini, E. W. Meijer, S. Di Stefano, Macromolecules 2015, 48, 1358–1363.

• Applications of Dynamic Combinatorial Chemistry for the Determination of Effective Molarity

M. Ciaccia, I. Tosi, L. Baldini, R. Cacciapaglia, L. Mandolini, S. Di Stefano, C. A. Hunter, Chemical Science 2015, 6, 144–151.

 Addition of chain‑stoppers to diluted Dynamic Libraries allows determination of EM of macrocycles.

• • Mechanisms of imine exchange reactions in organic solvents

M. Ciaccia, S. Di Stefano, Organic & Biomolecular Chemistry 2015, 13, 646–654.

Updated mechanisms operating in imine chemistry in organic solvents are reviewed and critically discussed.