Metal-organic frameworks (MOFs) are crystalline synthetic porous materials formed by binding organic linkers to metal nodes: they can be either rigid 1,2 or flexible. 3 Zeolites and rigid MOFs have widespread applications in sorption, separation and catalysis that arise from their ability to control the arrangement and chemistry of guests in their pores via the shape and functionality of the internal surface defined by their chemistry and structure. 4,5 Their structures correspond to an energy landscape with a single, albeit highly functional, energy minimum. In contrast, proteins function by navigating between multiple metastable structures using bond rotations of the polypeptide, 6,7 where each structure lies in one of the minima of a conformational energy landscape and can be selected according to the chemistry of the molecules interacting with the protein. These structural changes are realised through the mechanisms of conformational selection (where a higher energy minimum characteristic of the protein is stabilised by small molecule binding), and induced fit (where a small molecule imposes a structure on the protein that is not a minimum in the absence of that molecule). 8 Here we show that rotation about covalent bonds in a peptide linker can change a flexible MOF to afford nine distinct crystal structures, revealing a conformational energy landscape characterised by multiple structural minima. The uptake of small molecule guests by the MOF can be chemically triggered by inducing peptide conformational change. This change transforms the material from a minimum on the landscape that is inactive for guest sorption to an active one. Chemical control of the conformation of a flexible organic linker offers a route to modify the pore geometry and internal surface chemistry and thus the function of open-framework materials. Flexible MOF structures 9,10 can be rearranged in the presence of guests through mechanical mechanisms such as the repositioning of a rigid linker about an inorganic unit 11-13 or the relative displacement of two rigid networks, 14 opening a range of routes to control function 15 that are not accessible to rigid frameworks with their single structural minimum (Figure 1). Similar phenomena have been observed in the host-guest chemistry of interlocked cage molecules. 16-18 Alternatively, rotations about bonds involving sp 3 carbons 19-25 allow MOF to access different structures. For example, low energy conformational changes of dipeptide Gly-X linkers produce open and closed forms of Zn(Gly-X)2 frameworks. 26,27 The greater chemical diversity and more complex conformational space of higher order oligopeptides offer MOF with multiple open structures (Figure 1). This could allow interaction with molecules in the pores to select a specific structure for a defined function from the resulting energy landscape. That structure would be accessed through the single bond rotation pathway used by proteins (Figure 1). The tripeptide glycine-glycine-L-histidine (GGH) affords a three-dimensional chiral MOF Zn...

We report the use of a chiral Cu(II) 3D metal-organic framework (MOF) based on the tripeptide Gly-l-His-Gly (GHG) for the enantioselective separation of metamphetamine and ephedrine. Monte Carlo simulations suggest that chiral recognition is linked to preferential binding of one of the enantiomers as a result of either stronger or additional H-bonds with the framework that lead to energetically more stable diastereomeric adducts. Solid-phase extraction of a racemic mixture by using Cu(GHG) as the extractive phase permits isolating >50% of the (+)-ephedrine enantiomer as target compound in only 4 min. To our knowledge, this represents the first example of a MOF capable of separating chiral polar drugs.

Porous materials are attractive for separation and catalysis-these applications rely on selective interactions between host materials and guests. In metal-organic frameworks (MOFs), these interactions can be controlled through a flexible structural response to the presence of guests. Here we report a MOF that consists of glycyl-serine dipeptides coordinated to metal centres, and has a structure that evolves from a solvated porous state to a desolvated non-porous state as a result of ordered cooperative, displacive and conformational changes of the peptide. This behaviour is driven by hydrogen bonding that involves the side-chain hydroxyl groups of the serine. A similar cooperative closure (reminiscent of the folding of proteins) is also displayed with multipeptide solid solutions. For these, the combination of different sequences of amino acids controls the framework's response to the presence of guests in a nonlinear way. This functional control can be compared to the effect of single-point mutations in proteins, in which exchange of single amino acids can radically alter structure and function.

AbstarctCovalent organic frameworks (COFs) are network polymers with long-range positional order whose properties can be tuned using the isoreticular chemistry approach. Making COFs from strong bonds is challenging because irreversible rapid formation of the network produces amorphous materials with locked-in disorder. Reversibility in bond formation is essential to generate ordered networks, as it allows the error-checking that permits the network to crystallise, and so candidate network-forming chemistries such as amide that are irreversible under conventional low temperature bond-forming conditions have been underexplored. Here we show that we can prepare two- and three-dimensional covalent amide frameworks (CAFs) by devitrification of amorphous polyamide network polymers using high-temperature and high-pressure reaction conditions. In this way we have accessed reversible amide bond formation that allows crystalline order to develop. This strategy permits the direct synthesis of practically irreversible ordered amide networks that are stable thermally and under both strong acidic and basic hydrolytic conditions.

The peptide-based porous 3D framework, ZnCar, has been synthesized from Zn 2+ and the natural dipeptide carnosine (b-alanyl-l-histidine). Unlike previous extended peptide networks, the imidazole side chain of the histidine residue is deprotonated to afford Zn-imidazolate chains, with bonding similar to the zeolitic imidazolate framework (ZIF) family of porous materials. ZnCar exhibits permanent microporosity with a surface area of 448 m 2 g À1 , and its pores are 1D channels with 5 openings and a characteristic chiral shape. This compound is chemically stable in organic solvents and water. Single-crystal X-ray diffraction (XRD) showed that the ZnCar framework adapts to MeOH and H 2 O guests because of the torsional flexibility of the main His-b-Ala chain, while retaining the rigidity conferred by the Zn-imidazolate chains. The conformation adopted by carnosine is driven by the H bonds formed both to other dipeptides and to the guests, permitting the observed structural transformations.Metal-organic frameworks (MOFs) are crystalline porous materials composed of inorganic nodes, either single ions or clusters of ions, bridged by organic linkers through metalligand coordination bonds. [1] Recently, several biomolecules, such as amino acids, [2] nucleobases, [3] saccharides, [4] and peptides, [5] were used as organic linkers in MOF synthesis, mainly because of the diversity of their metal binding sites. The incorporation of biomolecules in MOFs also attracts particular attention because they can improve the biocompatibility of the final products, enhance the structural and chemical diversity of the internal surfaces of MOFs, and afford chiral frameworks that may have unique separation and catalytic properties. [6] Peptides are particularly interesting as linkers because dipeptides with hydrophobic residues that are held together by H bonds form metal-free purely peptide-based porous materials. These structures are divided into two groups, the Val-Ala compounds with hydrophobic pores and the Phe-Phe compounds with hydrophilic pores. [7] The Val-Ala structures exhibit typical CO 2 and CH 4 adsorption for microporous materials. [8] In MOFs, peptides have the ability to act as connecting ligands as they have at least one amino and one carboxylic acid terminus that can coordinate metal ions. The dipeptides Gly-Ala and Gly-Thr thus connect Zn 2+ ions to form two topologically distinct 2D-layered framework compounds, Zn(Gly-Ala) 2 and Zn(Gly-Thr) 2 , respectively. [9] The former is a flexible porous material that displays an adaptable pore conformation, which evolves continuously from an open to a partially disordered closed structure in response to the level of guest loading. The latter is structurally rigid to guest loss in a manner characteristic of rigid MOFs and exhibits permanent porosity with a surface area of 200 m 2 g À1 after solvent removal, as the framework is stabilized by the additional H bonding between the OH functional group from the threonine side chain and the NH 2 terminal group. These two e...