In the past decade, multicomponent reactions have experienced a renaissance as powerful peptide macrocyclization tools enabling the rapid creation of skeletal complexity and diversity with low synthetic cost. This review provides both a historical and modern overview of the development of the peptide multicomponent macrocyclization as a strategy capable to compete with the classic peptide cyclization methods in terms of chemical efficiency and synthetic scope. We prove that the utilization of multicomponent reactions for cyclizing peptides by either their termini or side chains provides a key advantage over those more established methods; that is, the possibility to explore the cyclic peptide chemotype space not only at the amino acid sequence but also at the ring-forming moiety. Owing to its multicomponent nature, this type of peptide cyclization process is well-suited to generate diversity at both the endo-and exo-cyclic fragments formed during the ring-closing step, which stands as a distinctive and useful characteristic for the creation and screening of cyclic peptide libraries. Examples of the novel multicomponent peptide stapling approach and heterocycle ring-forming macrocyclizations are included, along with multicomponent methods incorporating macrocyclization handles and the one-pot syntheses of macromulticyclic peptide cages. Interesting applications of this strategy in the field of drug discovery and chemical biology are provided.

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The hydrogen storage in zeolite-like hexacyanometalates with different exchangeable alkali metals within the cavities was studied. The H 2 adsorption isotherms were recorded at 75 and 85 K in order to estimate the involved adsorption heats using the isosteric method. The electric field gradient within the porous framework favors the hydrogen adsorption in the materials under study but also could lead to kinetic effects for the pore filling. Such effects were particularly pronounced for sodium among the studied compositions: Zn 3 A 2 [Fe-(CN) 6 ] 2 (A ) Na + , K + , Rb + , Cs + ) and Zn 3 [Co(CN) 6 ] 2 . For Na + , a strong interaction with the H 2 molecule takes place, where appreciable kinetic effects even at 258 K are observed. For Zn 3 [Co(CN) 6 ] 2 (rhombohedral phase) where the cavities are free of exchangeable metal and, in consequence, have a weak electric field gradient on their surface, the largest hydrogen storage capacity, close to 12 H 2 molecules per cavity (1.82% by weight), was observed. The hydrogen adsorption in these materials involves adsorption heats in the 6-8.5 kJ/mol range, following the order K > Rb > Cs ≈ Zn 3 [Co(CN) 6 ] 2 . The porous framework of this family of materials is formed by ellipsoidal cavities communicated by elliptical windows. The alkali metals are sited close to the windows. The pore accessibility and pore volume were evaluated from CO 2 adsorption isotherms recorded at 273 K. The free volume was found to be accessible to the CO 2 molecule for all of the studied compositions. According to the obtained isotherms the stabilization of the CO 2 molecule within the pores is caused by the electrostatic interaction between the electric field gradient at the cavity and the adsorbate quadrupole moment. The estimated strength for the guest-host interaction and the accessible pore volume follow the order Na > K > Rb > Cs. The largest accessible pore volume was found for Zn 3 [Co(CN) 6 ] 2 , close to 8 CO 2 molecules per cavity (28% by weight), but with the weaker guest-host interaction. The materials under study were characterized from X-ray diffraction, thermo-gravimetric, infrared, and Mo ¨ssbauer data. The obtained results shed light on the role of the electric field gradient at the cavity for the hydrogen adsorption.

The hydrogen adsorption in porous Prussian blue analogues shows the highest value for copper, suggesting the possibility that a direct interaction between the copper atom and the hydrogen molecule is established. The bonding of copper (2+) to the CN group of cyanometallates shows a unique behavior. The trend of copper to receive electrons in its 3d hole to adopt an electronic configuration close to 3d 10 is complemented by the ability of the CN group to donate electrons from its 5σ orbital, which has certain antibonding character. Because of this cooperative effect, the electronic configuration of the copper atom at the cavity surface is close to Cu(+). The resulting large availability of electron density on the copper atom favors its interaction with the antibonding σ* orbital of the hydrogen molecule. The charge removed from the metal t 2g orbitals is compensated (donated) by H 2 through a side-on σ interaction. From these combined mechanisms, where H 2 behaves as an acceptor-donor ligand for the copper atom, the high ability that copper hexacyanometallates show for the hydrogen storage could be explained. This hypothesis is supported by the obtained hydrogen adsorption data for Cu 3 [Ir(CN) 6 ] 2 , Cu 3 [Fe(CN) 6 ] 2 , Cu 2 [Fe(CN) 6 ], Cu[Pt(CN) 6 ], and Cu 3-x Mn x [Co(CN) 6 ] 2 , where 0 e x e 3, and also by the estimated values for the involved adsorption heats. The studied samples were previously characterized using X-ray diffraction, thermogravimetry, and infrared and Mo ¨ssbauer spectroscopies.