Ionic Liquids in Pharmaceutical and Biomedical Applications: A Review.

The unique properties of ionic liquids (ILs), such as structural tunability, good solubility, chemical/thermal stability, favorable biocompatibility, and simplicity of preparation, have led to a wide range of applications in the pharmaceutical and biomedical fields. ILs can not only speed up the chemical reaction process, improve the yield, and reduce environmental pollution but also improve many problems in the field of medicine, such as the poor drug solubility, product crystal instability, poor biological activity, and low drug delivery efficiency. This paper presents a systematic and concise analysis of the recent advancements and further applications of ILs in the pharmaceutical field from the aspects of drug synthesis, drug analysis, drug solubilization, and drug crystal engineering. Additionally, it explores the biomedical field, covering aspects such as drug carriers, stabilization of proteins, antimicrobials, and bioactive ionic liquids.

An in situ masking strategy enables radical monodecarboxylative C-C bond coupling of malonic acid derivatives.

The utilization of malonic acids in radical decarboxylative functionalization is still underexploited, and the few existing examples are primarily limited to bisdecarboxylative functionalization. While radical monodecarboxylative functionalization is highly desirable, it is challenging because of the difficulty in suppressing the second radical decarboxylation step. Herein, we report the successful radical monodecarboxylative C-C bond coupling of malonic acids with ethynylbenziodoxolone (EBX) reagents enabled by an in situ masking strategy, affording synthetically useful 2(3H)-furanones in satisfactory yields. The keys to the success of this transformation include (1) the dual role of a silver catalyst as a single-electron transfer catalyst to drive the radical decarboxylative alkynylation and as a Lewis acid catalyst to promote the 5-endo-dig cyclization and (2) the dual function of the alkynyl reagent as a radical trapper and as an in situ masking group. Notably, the latent carboxylate group in the furanones could be readily released, which could serve as a versatile synthetic handle for further elaborations. Thus, both carboxylic acid groups in malonic acid derivatives have been well utilized for the rapid construction of molecular complexity.

Three-dimensional ionic liquid-ferrite functionalized graphene oxide nanocomposite for pipette-tip solid phase extraction of 16 polycyclic aromatic hydrocarbons in human blood sample.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously found in the environment and have been proved to be prospectively associated with the risk of cancer. In this study, a simple method based on pipette-tip solid phase extraction (PT-SPE) and gas chromatography-mass spectrometry (GC-MS) has been firstly developed for the determination of 16 PAHs in human whole blood. Three-dimensional ionic liquid-ferrite functionalized graphene oxide nanocomposite (3D-IL-Fe3O4-GO) was used as sorbent in PT-SPE. Compared with conventional SPE method, the PT-SPE method was solvent-saving (1.0 mL), reusable (at least 10 times) and required less blood sample (200 µL). Affecting parameters on extraction efficiency were investigated and optimized. Under the optimized conditions, a good linearity was obtained and the recoveries of 16 PAHs at three spiked levels ranged from 85.0% to 115%. The limits of quantification (LOQs) were in the range of 0.007-0.013 µg/L. Furthermore, the developed method was successfully applied to the analysis of 16 PAHs in 14 human blood samples. The results showed that the predominant PAHs in human whole blood was low-molecular-weight PAHs, with the rank order phenanthrene (PHE)> naphthalene (NAP)> fluorene (FLU)> fluoranthene (FLT)> pyrene (PYR). Because of its simplicity, accuracy and reliability, the PT-SPE method combined with GC-MS demonstrated the applicability for clinical analysis and provided more information for PAHs exposure studies.

Preparation, characterization and in vitro anticoagulant activity of corn stover xylan sulfates.

A new anticoagulant agent was prepared by introducing sulfate groups into corn stover xylan through homogeneous reactions. Three organic solvents, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and formamide (FA), were adopted as reaction media, with the assistance of LiCl. Structural characterization by FT-IR and 13CNMR showed that xylan sulfate (XS) could be successfully synthesized with SO3∙Pyridine (SO3∙Py) complexes sulfation reagent in the three media. The effect of sulfation temperature, sulfation time, media type and molar ratio of -SO3/-OH on the degree of substitution (DS) and degree of the polymerization (DP) were studied. DMF/LiCl were more effective than DMSO/LiCl and FA/LiCl in preparation of xylan sulfate with high DS. The optimal conditions for sulfation were obtained when SO3∙Py complex was added to DMF/LiCl with -SO3/-OH ratio of 1.5:1 and maintained at 50 °C for 3 h. Degree of polymerization of xylan was decreased during the sulfation process and DMF/LiCl offered the least xylan degradation as compared with DMSO/LiCl or FA/LiCl. Anticoagulant activities of the resultant xylan sulfates with different DS were evaluated by using activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Results indicated that the introducing of sulfate groups into xylan did endow the polysaccharides with anticoagulant activity. The APTT and TT of XS with DS of 1.20 reached 141 and 45.3 s at a dosage of 20 µg/mL, while the APTT and TT values for the blank sample were only 35.5 and 15.6 s. Furthermore, coagulation time was prolonged with the increase of DS and the concentration of XS. Our findings provide new insights into the value-added utilization of agricultural biomass.