Green Synthesis Of Various Modified Cucurbiturils Under Mechanochemical Ball Milling

Cucurbitnuril is another high-profile macrocyclic supermolecular compound after crown ether and cyclodextrin.At present,the research in the polymer self-assembly field etc has made considerable progress.Cucurbitnuril,with one hydrophobic cavity and two polar carbonyl-modified ports,has the functions of host molecules due to its structural characteristics,which can not only contain organic molecules with appropriate size and structure to form unique cucurbituril host-guest chemistry,but be used as a ligand molecule to coordinate with metal ions and their complex or cluster compounds to form a unique cucurbituril coordination chemistry.In recent years,cucurbituril has been widely studied and applied due to its functions as a new type of drug carrier based on the host-guest interaction with drug molecules.The physicochemical properties of drugs are changed through host-guest inclusion to improve drugs' release performance so as to enhance efficacy and bioavailability and reduce side effects.Traditionally speaking,cucurbituril is synthesized by heat condensation of glycoside and paraformaldehyde under strong acidic conditions.This process is characterized by large pollution,high energy consumption and high synthesis cost,all of which also limit its application in many fields.However,mechanochemistry,as an emerging green chemical reaction method,can promote the efficient heterogeneous chemical reaction in a solvent-free or micro-solvent environment,and realize the some difficult conversions in the conventional solution environments.The mechanochemical ball milling was used to synthesize six-membered cucurbituril under acid-free green conditions with high efficiency and selectivity.Further,the response surface method was adopted to determine the optimal reaction conditions for synthesis.This process is characterized by short reaction time,little pollution,low energy consumption and high efficiency,which is suitable for synthesis from gram to kilogram products.This greatly reduces synthesis cost,and provides an outstanding way to obtain high-purity cucurbituril more conveniently,safely and efficiently.Meanwhile,due to its unique structural properties,cucurbituril is only soluble under strong acidic conditions with extremely poor performance in most of organicsolvents,which obviously restricts its abilities of containing and coordinating other molecules.Various modified cucurbiturils can be obtained by substituting hydrogen at the waist,which can improve the solubility under non-acidic conditions and expand the application range.The existing researches have mainly studied various simple and small hindered aliphatic substitutions on cucurbituril with few reports of large hindered aromatics.Based on the synthesis of diversified modified glycolurils,the mechanochemical method was applied to synthesize aliphatic substituted cucurbiturils such as all-methyl substituted cucurbituril,all-ethyl substituted cucurbituril,all-cyclohexyl substituted cucurbituril etc as well as aromatics,such as all-phenyl substituted cucurbituril,all p-methylphenyl substituted cucurbituril and all p-methoxyphenyl substituted cucurbituril together with large hindered modified cucurbituril.The newly modified cucurbituril was characterized by NMR,MS,TEM and SEM.