Applications Of Metal-Organic Frameworks In Research Of Biological Functional Molecules

Metal-Organic Frameworks?MOF?are regarded as excellent vectors due to its diverse pore environment.When compared to traditional porous materials such as mesoporous silica and mesoporous carbon,it is much easier to precisely tune the pore environment and achieve higher functionality of guest molecules.According to the literatures about loading of guest molecules,most of them just focus on the ability of guest molecule uptake so far.While there is lack of precise design and manipulation of pore environment,leading to an inefficient way to achieve the functionality of guest molecules.Here we take the small inert gas molecule and the small multi-component organic molecules as reaseach foundation.Then the three-dimensional bio-macromolecule?DNA?was applied as the final target,focusing on the study of compatibility and interaction between guest molecules and vectors with different pore sizes and functional groups.Based on the results,we hope to build a preliminary study on the customized design for microscopic guest molecules across to the mesoscopic guest molecules.The main contents and innovations including:1.Vector design for hyperpolarized ¹²⁹Xe.For hyperpolarized ¹²⁹Xe applied in biological magnetic resonance imaging,the hyperpolarized ¹²⁹Xe,the microporous materials?pore size<2 nm?is selected,finding that the Zeolitic Imidazolate Frameworks?ZIF-8?exhibit excellent interaction environment for ¹²⁹Xe.The particle size of ZIF-8 is tuned in order to improve its dispersibility in aqueous system and manipulate the interaction between hyperpolarized ¹²⁹Xe and ZIF-8,leading to a significant increase of Nuclear Magnetic Resonance?NMR?signal.2.Vectors for multi-component catalyst.For two-dimensional guest molecules,the metal catalyst,a organic linker named 4,4'-?pyrazine-2,5-diyl?bis?2-hydroxybenzoic acid??short for PDC?is designed to be synthesized,containing the pyrazine group.This linker is used to synthesize the mesoporous MOF,WHU-74,which exhibit a pore size around 2.4 nm.The Powder X-ray Diffraction?PXRD?Pattern of WHU-74demonstrated the structure that is similar to IRMOF-74-? as reported,exhibiting a hexagonal pore in one direction that is suitable for the uptake and release of guest molecules.X-ray photoelectron spectroscopy?XPS?is used to confirm the distribution pattern of metal catalyst.And the metal catalyst combined with the adjacent amine molecules coordinated to open metal site achieved a high efficiency and high selectivity confirmed by Gas Chromatography-Mass spectra?GC-MS?.3.Synthesis of linkers in IRMOF-74 series.The terminals both contain the structure of salicylic acid.The numbers of benzene rings were chosen as their features,named as ?,?,?,? corresponding to the length increase of linkers.We used 4-bromo-2-hydroxybenzoic acid and 4-bromo-2-methoxybenzoate as initial ingredient.Then the carboxylic group and hydroxyl group were protected by ester group and benzyl group,respectively.Next the gradual length increase of organic linkers is realized by Suzuki coupling reaction,the products of which is confirmed by high-resolution mass spectra?HRMS?and NMR technique.4.Synthesis and characterization of Ni-IRMOF-74 series and interaction study with DNA.According to the synthetic method of Mg-IRMOF-74 series,we have optimized the synthetic method of Ni-IRMOF-74 series,which help us obtain Ni-IRMOF-74 series with high crystallinity and high surface area.Through the observation on the fluorescence intensity change of fluorescence-labeled DNA after adding MOF material,we find that Ni-IRMOF-74-?,Ni-IRMOF-74-?,Ni-IRMOF-74-? and Ni-IRMOF-74-? can efficiently bind with DNA except for the Ni-MOF-74 with pore size smaller than the diameter of DNA.When the complementary sequence of DNA is added respectively to the complexes above,the fluorescence intensity recover the best among them,indicating the highest release efficiency of DNA and a suitable interaction between DNA and MOF pores.By utilizing the PXRD and fluorescence quench experiments,we primarily built the interaction mechanism between the pore structure and bio-macromolecule?DNA?and achieved highly efficient transfection.