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Vaccines induce specific immunity through antigen uptake and processing. However, while nanoparticle vaccines have elevated uptake, the impact of intracellular protein release and how this affects processing and downstream responses are not fully understood. Herein, we reveal how tuning unmodified antigen release rate, specifically through modulation of metal–organic framework (MOF) pore size, influences the type and extent of raised adaptive immunity. We use two MOFs in the NU-100x series with 1.4 nm difference in pore diameter, employ facile postsynthesis loading to achieve significant internalization of model protein antigen ovalbumin (ca.1.4 mg/mg), and observe distinct antigen release and intracellular processing profiles influenced by MOF pore size. We investigate how this difference in release biases downstream CD8⁺, T_H1, and T_H2 T cell responses. Ovalbumin-loaded NU-1003 induced 1.8-fold higher CD8⁺:CD4⁺T cell proliferation ratio and displayed 2.2-fold greater ratio of CD4⁺T_H1:T_H2 cytokines compared to ovalbumin-loaded NU-1000. Antigen released from NU-1000 in vivo exhibited stronger antigen-specific IgG responses, which is dependent on CD4⁺T cells (up to ninefold stronger long-term antibody production and 5.9-fold higher IgG1:IgG2a ratio), compared to NU-1003. When translated to wild-type SARS-CoV-2 receptor-binding domain (RBD) protein, RBD-loaded NU-1000 induced 60.5-fold higher IgG1:IgG2a compared to NU-1003. Wild-type RBD-loaded NU-1000 immunization also induced a greater breadth of epitope recognition compared to NU-1003, as evidenced by increased binding antibodies to the Omicron RBD variant. Overall, this work highlights how antigen release significantly influences immunity induced by vaccines and offers a path to employ unmodified antigen release kinetics to drive personalized protective responses. 

Enzymatic cascades play a crucial role in energy conversion and chemical transformations in living organisms. Due to enzymes’ high selectivity in catalysis and eco-friendly nature, operating enzymatic cascades in cell-free systems has the potential to improve existing chemical transformations. However, applications involving enzymes are often limited by their poor stability in cell-free environments, and the impact of immobilization on the kinetics of enzymatic cascades remains relatively underexplored, largely due to challenges in determining the support structure and controlling the enzyme immobilization process. In this work, we developed NU-1510-Cr, a chromium-based mesoporous metal–organic framework (MOF) with the mtn topology to encapsulate an enzyme cascade that oxidizes ethanol to acetaldehyde and subsequently to acetic acid. The crystalline hierarchical pores provide spatial control of the enzymes within the host, where the impact of the spatial organization on the cascaded reaction kinetics was assessed. The findings offer valuable insights for those aiming to immobilize and compartmentalize biocatalytic or chemocatalytic cascade systems and develop efficient microscale and nanoscale bioreactors. 

The quest for understanding the structure-property correlation in porous materials has remained a persistent focus across various research domains, particularly within the sorption realm. Molecular metal oxide clusters, owing to their precisely tunable atomic structures and long-range order, exhibit significant potential as versatile platforms for sorption investigations. This study presents a series of isostructural Ti8Ce2-oxo clusters with subtle variations in coordinated linkers and explores their gas sorption behavior. Notably, Ti8Ce2-BA (where BA denotes benzoic acid) manifests a distinctive twostep profile during CO2 adsorption, accompanied by a hysteresis loop. This observation marks a pioneering instance within the metal oxide cluster field. Of particular intrigue, the presence of unsaturated Ce(Ⅳ) sites was found to be correlated with the stepped sorption property. Moreover, the introduction of an electrophilic fluorine atom, positioned ortho or para to the benzoic acid, facilitated precise control over gate pressure and stepped sorption quantities. Advanced in-situ techniques systematically unraveled the underlying mechanism behind this unique sorption behavior. The findings elucidate that robust Lewis base-acid interactions are established between CO2 molecules and Ce ions, consequently altering the conformation of coordinated linkers. Conversely, the F atoms primarily contribute to gate pressure variation by influencing the Lewis acidity of the Ce sites. This research advances the understanding in fabricating geometrically "flexible" metal-oxo clusters and provides profound insights into their host-guest interaction motifs. These insights hold substantial promise across diverse fields, particularly in CO2 gas capture and gas-phase catalysis, and offer valuable guidance for future adsorbent designs grounded in fundamental theories of structure-property relationships. 

Catalysis using earth abundant metals is an important goal due to the relative scarcity and expense of precious metal catalysts. It would be even more beneficial to use earth abundant catalysts for the synthesis of common pharmaceutical structural motifs such as pyrrolidine and pyridine. Thus, developing titanium catalysts for asymmetric ring closing hydroamination is a valuable goal. In this work, four sterically encumbered chiral sulfonamides derived from naturally occurring amino acids were prepared. These compounds undergo protonolysis reactions with Ti(NMe 2 ) 4 or Ta(NMe 2 ) 5 to give monomeric complexes as determined by both DOSY NMR and X-ray crystallography. The resulting complexes are active for the ring closing hydroamination hepta-4,5-dienylamine to give a mixture of tetrahydropyridine and pyrrolidine products. However, the titanium complexes convert 6-methylhepta-4,5-dienylamine exclusively to 2-(2-methylpropenyl)pyrrolidine in higher enantioselectivity than those previously reported, with enantiomeric excesses ranging from 18-24%. The corresponding tantalum complexes were more selective with enantiomeric excesses ranging from 33-39%. 

Alkylation of d - or l -phenylalanine or valine alkyl esters was carried out using methyl or phenyl Grignard reagents. Subsequent condensation with salicylaldehyde, 3,5-di- tert -butylsalicylaldehyde, or 5-fluorosalicylaldehyde formed tridentate, X 2 L type, Schiff base ligands. Chiral shift NMR confirmed retention of stereochemistry during synthesis. X-ray crystal structures of four of the ligands show either inter- or intramolecular hydrogen bonding interactions. The ligands coordinate to the titanium reagents Ti(NMe 2 ) 4 or TiCl(NMe 2 ) 3 by protonolysis and displacement of two equivalents of HNMe 2 . The crystal structure of one example of Ti(X 2 L)Cl(NMe 2 ) was determined and the complex has a distorted square pyramidal geometry with an axial NMe 2 ligand. The bis-dimethylamide complexes are active catalysts for the ring closing hydroamination of di- and trisubstituted aminoallenes. The reaction of hepta-4,5-dienylamine at 135 °C with 5 mol% catalyst gives a mixture of 6-ethyl-2,3,4,5-tetrahydropyridine (40–72%) and both Z - and E -2-propenyl-pyrrolidine (25–52%). The ring closing reaction of 6-methyl-hepta-4,5-dienylamine at 135 °C with 5 mol% catalyst gives exclusively 2-(2-methyl-propenyl)-pyrrolidine. The pyrrolidine products are obtained with enantiomeric excesses up to 17%.