Seven Post-synthetic Covalent Reactions in Tandem Leading to Enzyme-like Complexity within Metal-Organic Framework Crystals

Abstract

The design of enzyme-like complexity within metal-organic frameworks (MOFs) requires multiple reactions to be performed on a MOF crystal without losing access to its interior. Here, we show that seven post-synthetic reactions can be successfully achieved within the pores of a multivariate MOF, MTV-IRMOF-74-III, to covalently incorporate tripeptides that resemble the active sites of enzymes in their spatial arrangement and compositional heterogeneity. These reactions build up H2N-Pro-Gly-Ala-CONHL and H2N-Cys-His-Asp-CONHL (where L = organic struts) amino acid sequences by covalently attaching them to the organic struts in the MOFs, without losing porosity or crystallinity. An enabling feature of this chemistry is that the primary amine functionality (-CH2NHBoc) of the original MOF is more reactive than the commonly examined aromatic amines (-NH2), and this allowed for the multi-step reactions to be carried out in tandem within the MOF. Preliminary findings indicate that the complexity thus achieved can affect reactions that were previously accomplished only in the presence of enzymes.

Figure 1

(a) PXRD patterns for simulated IRMOF-74-III (black), starting material MTV-(CH₃)_0.6(CH₂NHBoc)_0.4 (blue), and product after seven post-synthetic reactions, [MTV-(CH₃)_0.6(CH₂NH-Ala-Gly-Pro-NH₂)_0.2 (red). (b) N₂ isotherms at 77 K for MTV-(CH₃)_0.6-(CH₂NHBoc)_0.4 (blue) and MTV-(CH₃)_0.6(CH₂NH-Ala-Gly-Pro-NH₂)_0.2 (red).

Figure 2

(a) Catalytic cleavage of pentapeptide 1 by Cat. C [MTV-IRMOF-74-III-(CH₃)_0.6(CH₂NH-Asp-His-Cys-NH₂)_0.1] in the specific sequence containing serine. (b) Cartoon representation of the enzyme TEV endoprotease, highlighting the three amino acids that participate in the catalysis.

Scheme 1. Seven Post-synthetic Reactions to Achieve Enzyme-like Complexity in the Pores of MTV-IRMOF-74-III-(CH₃)_0.6(CH₂NHBoc)_0.4^a

^a(a) Polyhedral drawing of −CH₂NHBoc functionalized MOF pore. (b) Post-synthetic reactions (1)–(7) are illustrated using a van der Waals surface: thermal Boc deprotections for (1), (3), (5), and (7); amino acid loading steps for (2), (4), and (6) (Ala, Gly, and Pro, respectively). The evolution of one potential reaction byproduct (i.e., dipeptide H₂N-Pro-Gly-CONHL) is represented in gray. These byproducts, due to incomplete post-synthetic transformations, also affect the molecular formula of the compounds, as can be noted in the scheme.