Robust protein-nanomaterial surface analysis is important, but also a challenge. Thrombin plays an important role in the coagulant activity of protein corona mediated by Ca2+ ion exchanged zeolites. However, the mech-anism for this modulation remains unresolved. In this study, we proposed a combined computational and experimental approach to determine the adsorbed sites and orientations of thrombin binding to Ca2+-exchanged LTA-type (CaA) zeolite. Specifically, fourteen ensembles of simulated annealing molecular dynamics (SAMD) simulations and experimental surface residues microenvironment analysis were used to reduce the starting orientations needed for further molecular dynamics (MD) simulations. The combined MD simulations and pro -coagulant activity characterization also reveal the consequent corresponding deactivation of thrombin on CaA zeolite. It is mainly caused by two aspects: (1) the secondary structure of thrombin can change after its adsorption on the CaA zeolite. (2) The positively charged area of thrombin mediates the preferential interaction between thrombin and CaA zeolite. Some thrombin substrate sites are thus blocked by zeolite after its adsorption. This study not only provides a promising method for characterizing the protein-nanoparticle interaction, but also gives an insight into the design and application of zeolite with high procoagulant activity.

Understanding of drug–carrier interactions is essential for the design and application of metal–organic framework (MOF)-based drug-delivery systems, and such drug–carrier interactions can be fundamentally different for MOFs with or without defects. Herein, we reveal that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host–guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites, and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOFs without defects, the loading capacity is greatly reduced. We employed solid-state NMR spectroscopy and molecular simulations to elucidate the drug–carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects were revealed.

Metal-organic frameworks (MOFs) are porous crystalline materials with promising applications in molecular adsorption, separation, and catalysis. It has been discovered recently that structural defects introduced unintentionally or by design could have a significant impact on their properties. However, the exact chemical composition and structural evolution under different conditions at the defects are still under debate. In this study, we performed multidimensional solid-state nuclear magnetic resonance (SSNMR) coupled with computer simulations to elucidate an important scenario of MOF defects, uncovering the dynamic interplay between residual acetate and water. Acetate, as a defect modulator, and water, as a byproduct, are prevalent defect-associated species, which are among the key factors determining the reactivity and stability of defects. We discovered that acetate molecules coordinate to a single metal site monodentately and pair with water at the neighboring position. The acetates are highly flexible, which undergo fast libration as well as a slow kinetic exchange with water through dynamic hydrogen bonds. The dynamic processes under variable temperatures and different hydration levels have been quantitatively analyzed across a broad time scale from microseconds to seconds. The integration of SSNMR and computer simulations allows a precision probe into defective MOF structures with intrinsic dynamics and disorder.

Owing to the rigid standards of manufacturing semiconductor components, decrease of the moisture to parts-per-billion (ppb), at a global level, is always vital but extremely nerve-racking in the production of high-purity gases. Herein, typical adsorbents including oxides (SiO2 and gamma-Al2O3), zeolites (4A and NaX), and metal-organic frameworks (MOFs; HKUST-1, UiO-66, and ZIF-8) are investigated with respect to the abilities of ultradeep dewatering from N-2. Compared with other adsorbents, NaX performs much better on both dewatering efficiency (DE, from 2750 to 66 ppb) and the adsorption capacity (AC, 1.55 x 10(4) L N-2.g(-1)). Moreover, it is for the first time experimentally and theoretically proved that the dewatering ability of X zeolite mainly depends on its cation species (Na+, Li+, K+, Cs+, Mg2+, Ca2+, Sr2+, or Ba2+), the forces between the zeolite and H2O, and the number of H2O molecules per cell of the zeolite. CaX thus shows a fascinating DE from 2750 to 33 ppb, a huge AC of 9.08 x 10(4) L N-2.g(-1), and an ideal reusability, compared with results of the scarce contributions reported to date.

DNA has proven of high utility to modulate the surface functionality of metal-organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for preparing DNA-MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (∼2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA-MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was further armed by a protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG-MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential "protect-release" program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.

The improvement of the resolution of DNA sequencing by nanopore technology is very important for its real-life application. In this paper, we report our work on using molecular dynamics simulation to study the dependence of DNA sequencing on the translocation time of DNA through a graphene nanopore, using the single-strand DNA fragment translocation through graphene nanopores with diameters down to ∼2 nm as examples. We found that A, T, C, and G could be identified by the difference in the translocation time between different types of nucleotides through 2 nm graphene nanopores. In particular, the recognition of the graphene nanopore for different nucleotides can be greatly enhanced in a low electric field. Our study suggests that the recognition of a graphene nanopore by different nucleotides is the key factor for sequencing DNA by translocation time. Our study also indicates that the surface of a graphene nanopore can be modified to increase the recognition of nucleotides and to improve the resolution of DNA sequencing based on the DNA translocation time with a suitable electric field.