Design and Synthesis of Novel NO-Drug Hybrid Compound and Green Catalytic Activity Evaluation of Synthesized Silver Nanoparticle-Halloysite Nanocomposite

Abstract

Acetaminophen is a well-known analgesic that can manage pain and reduce fever. SCP-1 is a derivative of acetaminophen that showed significantly reduced hepatotoxicity and nephrotoxicity comparative to acetaminophen. Nitric oxides have been well known to play a key role in a wide variety of physiological and pathophysiological important processes. It was therefore of interest to synthesize a nitric oxide donor linked to SCP-1 that could have enhanced analgesic and antipyretic activity. A furoxan CAS 1609 as NO-donor was synthesized and linked to SCP-1 successfully. The furoxan CAS 1609 was initially synthesized from tetronic acid to give 1,2- dioxime in 86 % yield. The furoxan 4-hydroxymethyl carboxymethyl ester was obtained in 55 % yield by using t-butyl hypochlorite as an oxidation agent. The furoxan 4-hydroxymethyl carboxymethyl ester was treated with ammonia solution in methanol and converted the ester group into an amide moiety and furnish the targeted furoxan CAS 1609 in 98% yield. The CAS 1609 was coupled with SCP-1, after bromination of the hydroxyl group by thionyl bromide, using DBU as base at room temperature to produce NO-SCP-1 in 57%. Halloysite is a naturally available clay with a hollow tubular structure, and it is abundant and durable. Metallic nanoparticles supported by halloysite to form nanocomposite materials have huge potential in heterogeneous catalysis. Silver nanoparticles (~10 nm, AgNP) were synthesized inside the lumen of halloysite under green conditions to form Ag@Hal. The nanocomposite was characterized by Transmission Electron Microscopy and Inductively Coupled Plasma Atomic Emmision Spectroscopy and determined to be 6% Ag@Hal (wt/wt). The Ag@Hal nanocomposite exhibited catalytic activity and selectivity for the synthesis of 1,4-disubstituted over the 1,5- disubstituted triazoles under green condition. The reaction also showed enhanced over all yieldwhen the temperature was increased. The 1-benzyl-4-phenyl-1,2,3-triazole was obtained in 58% yield while the 1,5-disubstituted 1,2,3-triazole was isolated in 19% yield.