Strategy of Choosing Templates in Molecular Imprinting to Expand the Recognition Width for Family-Selectivity.

The class-selective molecular-imprinted polymers (MIPs) have shown the recognition ability to multiple targeted molecules through using one or multiple templates. However, choosing the right templates, the core problem, still lacks a systemic guide and decision-making. In this work, we propose a strategy of selecting templates through expanding the recognition width for the improvement of class-selectivity. First, three families of genotoxic impurity (GTI) were selected as model objects, and the spatial size and binding energy of each GTI-monomer complexes were obtained and compared by computational simulation. The two indexes of energy width (WE) and size width (WL) were introduced to compare the similarity and differences on the two recognition factors, binding strength and spatial size, among these GTIs in each family. Through shortening the width to increase similarity on binding energy and size, the dual templates in the aromatic amines (AI) family and sulfonic acid esters (SI) family were successfully selected. Correspondingly, the prepared dual-template MIPs in the two GTI families can simultaneously recognize all the GTIs comparing with that of single template MIP, respectively. Meanwhile, through comparing the adsorption capacity of the selected template and its analogues in one GTI family, the recognition efficiency of the dual-template MIPs was higher than that of the single-template MIP. This indicates that though using the selected right templates, the higher class-selectivity and the larger recognition width can be realized. Thus, this work can solve the problem of blind template selection, and provide the useful theoretical guidance for designing family-selective molecular imprinting.

Improved selectivity of molecularly imprinted polymers based on the synergistic action of hydrogen bond and electrostatic interaction.

Based on the synergistic action of hydrogen bond and electrostatic interaction, provided by methacrylic acid and 2-aminoethyl ester hydrochloride (FM2), respectively, novel molecularly imprinted polymers (SA-MIPs) were designed to improve its selective recognition ability. Diclofenac sodium (DFC) was chosen as the template molecule of this study. The interaction and their recognition sites between two functional monomers and templates were confirmed by nuclear magnetic resonance hydrogen spectroscopy. Because of the synergistic action of hydrogen bond and electrostatic interaction, the imprinting factor (IF) of SA-MIPs (IF = 2.26) is superior to the corresponding monofunctional monomer imprinting materials (IF = 1.52, 1.20) and the materials using two functional monomers with an only single type of interaction (IF = 1.54, 1.75). The results of selective adsorption experiments indicate that the selective recognition ability of SA-MIPs is significantly better than that of the other four MIPs, and the difference in selectivity coefficient for methyl orange is the largest between SA-MIPs and the MIPs only using FM2, which is about 70 times. In addition, x-ray photoelectron spectroscopy was used to verify the interaction between SA-MIPs and the template. This work and its explanation of the interaction mechanism at the molecular level will be helpful for the rational design of novel MIPs with higher selectivity. Besides, SA-MIPs have good adsorption performance (37.75 mg/g) for DFC in aqueous solutions, which could be used as potential adsorption materials for the effective removal of DFC in the aquatic environment.

Modification and characterization of a novel and fluorine-free cellulose nanofiber with hydrophobic and oleophobic properties.

In this study, a brand-new, easy, and environmentally friendly approach for chemically functionalizing 2,2,6,6-tetramethylpiperidinyloxyl radical (TEMPO)-oxidized cellulose nanofiber (TOCNF) to produce modified cellulose nanofiber (octadecylamine-citric acid-CNF) was proposed. Effects of octadecylamine (ODA)/TOCNF mass ratio on the chemical structure, morphology, surface hydrophobicity and oleophobicity were studied. According to Fourier transform infrared spectroscopy (FTIR) analysis, ODA was successfully grafted onto the TOCNF by simple citric acid (CA) esterification and amidation reactions. Scanning electron microscopy (SEM) showed that a new rough structure was formed on the ODA-CA-CNF surface. The water contact angle (WCA) and the castor oil contact angle (OCA) of the ODA-CA-CNF reached 139.6° and 130.6°, respectively. The high-grafting-amount ODA-CA-CNF was sprayed onto paper, and the OCA reached 118.4°, which indicated good oil-resistance performance. The low-grafting-amount ODA-CNF was applied in a pH-responsive indicator film, exhibiting a colour change in response to the pH level, which can be applied in smart food packaging. The ODA-CA-CNF with excellent water/oil-resistance properties and fluorine-free properties can replace petrochemical materials and can be used in the fields of fluorine-free oil-proof paper.

Synergistically improve the strength and porosity of carbon paper by using a novel phenol formaldehyde resin modified with cellulose nanofiber for proton exchange membrane fuel cells.

To optimize the imbalance between the interfacial bonding and porosity properties of carbon paper (CP) caused by phenol formaldehyde resin (PF) impregnation, and therefore improve the performance of proton exchange membrane fuel cells (PEMFCs), a new approach through cellulose nanofibers grafted with methyl methacrylate (CNFM) as a modified reinforcement and pore-forming agent for PF is investigated. Through suppressing the methylene backbone fracture of CNFM-modified PF during its thermal depolymerization, the interfacial bonding between PF matrix carbon and carbon fibers is enhanced. Compared with unmodified CP, the in-plane resistivity of CNFM-modified CP is reduced by 35.78 %, while the connected porosity increases to 82.26 %, and more homogeneous pore size distribution (PSD) in the range of 20-40 µm is obtained for CNFM-modified CP. Besides, the tensile strength, flexural strength, and air permeability of CNFM-modified CP increase by 72.78 %, 298.4 %, and 103.97 %, respectively. In addition, CNFM-modified CP achieves the peak power density of PEMFCs to 701.81 mW·cm-2, exhibiting 10.98 % improvement compared with commercial CP (632.39 mW·cm-2), evidently achieving an integral promotion of CP and comprehensive performance.

Preparation of dummy molecularly imprinted polymers for selective extraction of aromatic amine genotoxic impurities.

To ensure drug safety, the quality monitoring of genotoxic impurities (GTIs) which have very trace content in medicine is important. Therefore, it should be established an efficient sample pretreatment method to extract GTIs to achieve specific enrichment. In this work, dummy template molecular imprinting technology (DMIT) was used as dummy template molecule (DTM) to substitute for the target molecule (TM) for established the pretreatment of the sample containing aromatic amine GTIs. A novel strategy for screening out DTM by calculation of computer simulation is established, where the binding energy between the template and functional monomer has the relatively lowest value (-9.60 kcal/mol). Then dummy template molecular imprinted polymer (DMIP) was prepared by bulk polymerization according to the molar ratio of template molecule-functional monomer-crosslinker = 1:4:8, the prepared DMIP exhibited the highest adsorption (Q = 8.6 mg/g) and good blotting effect (IF = 1.3) and can simultaneously adsorb three aromatic amine GTIs. The optimal adsorption conditions were obtained by conditional optimization of solid phase extraction (SPE). The solution of pH 7 was chosen as the loading condition, and methanol/acetic acid (90:10, v/v) was chosen as the elution condition. Finally, we determined 2, 6-dichloroaniline in diclofenac sodium at a 5 ppm level and p-toluidine as the TMs in torasemide sample at 10 ppm by using DMIT-based solid phase extraction and analysis by HPLC, it satisfied the quality control of GTIs in pharmaceutics. DMIT by this strategy has great potential in the sample preparation of GTIs.

Development of Ussing model coupled with artificial membrane for predicting intestinal absorption mechanisms of drugs.

The absorption mechanisms of drugs play an important role on development and various application of drugs. However, the present methods of absorption mechanisms are not perfect enough. Hence, exploring a novel method to accurately predict the absorption mechanisms is necessary. In this study, we developed an Ussing model coupled with artificial membrane (AM-Ussing) for predicting the permeability of passive diffusion. Furthermore, by the combination of AM-Ussing and Ussing model, the three different mechanisms including efflux transport, uptake transport and passive diffusion could be successfully distinguished. Specifically, 12 drugs of passive transport were selected to evaluate AM-Ussing. And the high permeability correlation between AM-Ussing model and traditional Ussing model indicated that AM-Ussing was successfully established. Moreover, the absorption mechanisms of 11 drugs were predicted by the combination of AM-Ussing and Ussing model. The results showed that three kinds of absorption mechanisms mentioned can be predicted successfully. Therefore, AM-Ussing model is a potential tool to assess passive diffusion, and the combined use of AM-Ussing and Ussing model is an effective method to predict the intestinal absorption mechanisms of drugs.

In situ one-pot synthesis of polydopamine/octadecylamine co-deposited coating in capillary for open-tubular capillary electrochromatography.

Mussel-inspired polydopamine (PDA) based materials are attractive as stationary phase for open-tubular capillary electrochromatography (OT-CEC) due to their many fascinating properties. However, all of the existing strategies for fabricating PDA based OT-CEC columns are limited in aqueous solutions. Consequently, it is a challenge work to directly immobilize the hydrophobic functional materials onto the inner wall of PDA modified capillary. Herein, by using the organic amine-inducing co-deposition strategy, a novel preparative method was developed for in situ one-pot synthesis of PDA/octadecylamine (ODA) co-deposited coating inside capillary as OT-CEC stationary phase. The formation and morphology of the PDA/ODA co-deposited coating were characterized by field emission scanning electron microscopy, atomic force microscope, attenuated total reflectance Fourier transform infrared spectroscopy and contact angle measurements. The separation performance of the fabricated PDA/ODA modified columns was validated by the separation of alkylbenzenes and steroids, which could achieve baseline separation with high separation efficiency. Their separation was found to follow the reversed phase chromatographic retention mechanism. The co-deposited column showed good stability and long lifetime. The repeatability of the PDA/ODA co-deposited column was also evaluated, with the relative standard deviations for intra-day and inter-day runs less than 5% and column-to-column runs less than 6%.

Preparation of restricted access molecularly imprinted polymers based fiber for selective solid-phase microextraction of hesperetin and its metabolites in vivo.

A novel restricted access molecularly imprinted polymers (RAMIPs) fiber was developed for solid-phase microextraction (SPME) of hesperetin and its metabolites in livers of live rats in vivo. Hesperetin as the template, N-isopropylacrylamide as the functional monomer, ethylene glycol dimethyl acrylate as the crosslinker, 2,2-azobisisobutyonnitrile as initiator and bovine serum albumin as the restricted access material were applied in the preparation process. Scanning electron microscopy and Fourier transform infrared spectroscopy were applied to characterize the polymers. The adsorption experiments indicated that RAMIPs-SPME fibers performed high selective recognition property to hesperetin. The selectivity experiment indicated that the adsorption capacity and selectivity of RAMIPs-SPME fibers to hesperetin was higher than that of quercetin, luteolin and baicalein. Macromolecules elimination test showed RAMIPs-SPME fibers could eliminate 94.80%-98.96% of macromolecules, which indicated that RAMIPs-SPME fibers can be used to extract analytes directly from complex biological samples. Furthermore, RAMIPs-SPME sampling combined to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to capture and identify hesperetin and its metabolites in rat livers in vivo. Finally, hesperetin-7-O-glucuronide, hesperetin-3'-O-glucuronide, eriodictyol and homoeriodictyol were identified as the metabolites of hesperetin. In comparison with the MIPs fibers, commercial PDMS and DVB fibers, RAMIPs-SPME fibers possessed better exclusion effect to macromolecules and higher selectivity to hesperetin and its metabolites. The results demonstrated that the prepared RAMIPs-SPME fiber were proven to be effective tool for the selective adsorption and enrichment of hesperetin and its metabolites from the complex biological fluids.

Bioinspired affinity DNA polymers on nanoparticles for drug sequestration and detoxification.

Nanomaterials with the ability of sequestering target molecules hold great potential for a variety of applications. To ensure the stable sequestration, most of these nanomaterials have been traditionally designed with a clear boundary or compact structures and behave as closed systems. While this feature is beneficial to applications such as drug delivery, it may pose a challenge to applications where fast molecular transport from the environment to nanomaterials is critical. Thus, this study was aimed at exploring a nanomaterial with affinity DNA polymers and nanoparticles as an open system with function similar to jellyfish tentacles in sequestering target molecules from surroundings. The results show that this nanomaterial can effectively and rapidly sequester both small molecule drugs and large molecule biologics and resultantly mitigate their biological effects. Thus, this nanomaterial holds potential as a universal nanoscale antidote for drug removal and detoxification. While this nanomaterial was evaluated by using drug removal and detoxification as a model, the synthesis of periodically oriented affinity polymers on a nanoparticle with the capability of sequestering target molecules may be tuned for broad applications such as separation, sensing, imaging and drug delivery.