Construction of Spiro[benzo[a]acridine-12,4'-imidazolidine]-2',5'-dione Derivatives via Ring-Opening and Recyclization of Isatins and C-OH Cleavage of 2-Naphthol.

An efficient three-component reaction to access spiro[benzo[a]acridine-12,4'-imidazolidine]-2',5'-dione derivatives has been developed through the ring-opening and recyclization process of isatins and dehydroxylation of 2-naphthol, which is different from their conventional reaction modes. Experimental observations suggest that p-toluenesulfonic acid is the key factor that promotes the success of this synthetic strategy. The research provided a novel approach for the construction of spiro compounds from isatins and 2-naphthol in organic synthesis.

A mismatch-suppressed, duplex-specific nuclease powered nanowalker for multiplexed sensing of microRNA.

DNA molecular machines have attracted immense interest for their potential in biosensing, drug delivery, and cellular imaging. Herein, we report a duplex-specific nuclease (DSN) powered nanowalker that can autonomously and progressively move on a spherical three-dimensional track, which is constructed by functionalizing a 13 nm diameter gold nanoparticle (AuNP) with densely mismatched DNA duplexes. The motion is initiated by an RNA walking strand, and in its absence, the walker is suppressed because the DSN is inactive toward the mismatched DNA duplexes. Once the walking strand is added, perfectly matched DNA-RNA hybrid is formed via a toehold-mediated displacement reaction between the walking strand and mismatched duplex. Thereafter, the DNA-RNA hybrid is simultaneously cleaved by DSN, by releasing the walking strand, which autonomously moves on the track with the aid of DSN. The present study provides a novel energy input and power mechanism for the operation of 3-D nanowalker with high efficiency. Moreover, the proposed nanowalker can be designed in a target microRNA (miRNA)-specific manner by altering the mismatched duplexes, and it exhibits femtomole level sensitivity in both singleplexed and multiplexed sensing of three miRNA targets. In addition, multiplexed quantification of the three miRNAs in biological samples is achieved, further suggesting that the proposed nanowalker has immense potential in biomedical research and early diagnosis of clinical disorders.

MnO2 switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides.

Cholinesterases (ChEs) are important indicators of neurological disease, hepatocellular carcinoma, and organophosphate poisoning. In this work, a MnO2 switch-bridged DNA walker was developed for ultrasensitive sensing of ChEs activity. The fuel strands loaded MnO2 switch was designed to bridge the hydrolysis activity of ChEs and the running of the DNA walker. Under the action of ChE, the substrate butyrylcholine is first catalytically hydrolyzed to thiocholine, which then mediates MnO2 nanosheet reduction to Mn2+, releasing the fuel strands into solution. The fuel strands as substitute targets then trigger the continuous operation of DNA walker with the aid of Mn2+, generating detectable fluorescence responses. The detection of ChE activity is converted to DNA detection in this method. Benefited from the robust operation and amplification effect of DNA walker, a wide linear range between the BChE activity and fluorescence intensity of nearly six orders of magnitude (1000-0.005 U/mL) and a limit of detection as low as 0.0008 U/mL are achieved. This allows the direct determination of BChE activity in clinical serum samples without any pretreatments. Moreover, the proposed method has remarkable capabilities for inhibitor (organophosphorus pesticide) screening and quantification, and organophosphorus pesticide detection in real samples is also achieved. Therefore, the MnO2 switch-bridged DNA walker represents a powerful tool for ultrasensitive sensing of ChEs and organophosphorus pesticides, and has great application potential in clinical diagnosis, therapeutics, and drug screening.