Density Functional Studies On The Functionalization Of Carbon Nanotubes And Mechanism Of Their Delivery Of Anti-influenza Drugs

Drug delivery system is of great practical significance to improve the medicinal effects of natural products and their derivatives and theirs route of administration.Carbon nanotubes have become one of the research hotspots owing to the unique propensity to cross cell membranes,nuclear pore and biological barriers.However,there have been no related reports about drug delivery systems consisting of natural drugs and carbon nanotubes,and the interaction mechanism between them is still indeterminate.In this paper,density functional theory calculations(DFT)was conducted to study the functionalization of(5,5)single-walled carbon nanotube(SWCNT)and the interaction mechanism between(5,5)SWCNT and natural products derivatives,anti-influenza drug 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid(BA),in depth and systematically.On the basis,the interaction mechanism was verified that can be applied to other anti-influenza drug delivery systems.Therefore,the results of this paper will provide important theoretical and scientific ideas for the drug delivery systems of natural derivative drugs.In this paper,amino acids of human homologous substances were selected to functionalize(5,5)SWCNT,the functionalization systems,which had apparent merits such as small toxicity,easy absorption and low reactivity with drugs.In the glycine(Gly)and Al/SWCNT functionalization system,the order of functionalization sites declines as O_b>N>O_a,and there was a stable bidentate configuration NO_b.In all functionalization systems,Al/SWCNT could stabilize zwitterionic Gly with the greatest interaction energy-216.3 kJ/mol and render it to be the most stable configuration with the most interaction energy.Significant charge transfers occured during the functionalization of Al/SWCNT with Gly,and the amounts of charge transfers were in direct proportion with the strength of interaction.Moreover,the Gly and dopant atom Al center were electronic donors,while the carbon framework of Al/SWCNT acted as electronic acceptors.The above mechanism provides a theoretical basis for the study of Al/SWCNT in the drug delivery systems of natural derivative drugs.Considering a variety of types of dopants,various functionalization systems were established in this paper.After atom doping,the electron-accepting ability,reactivity of SWCNT were significantly improved,and conductivity was also dramatically enhanced.Functionalization efficiencies of Gly were directly determined by dopants,as a combined effect of atomic radius,electronic configuration and distortion to SWCNTs.Different functionalization sites in Gly had divergent interaction strengths with various metal atoms doping that decline as O_b>N>O_a,and this trend seems almost independent of the identity of metallic dopants.The functionalization system consists of zwitterionic Gly and Ca-doped SWCNT corresponding to the most interaction energy-248.6 kJ/mol.All functionalization systems except doped by B could stabilize zwitterionic Gly and render it to be the most stable one.In general,the amounts of charge transfer decreased with the increasing interaction energy.This study provides a valuable scientific basis for improving the reactivity of SWCNT's surface and functionalization efficiency of SWCNT.In this paper,the functionalization systems consisting of different amino acids and Al/SWCNT were build,finding that the amino acid side chains alter the priority of the functionalization sites radically.The side chain of aspartic acid(Asp)offered new functionalization sites,generating novel interaction mode O_d.Asp and Al/SWCNT functionalization system was the most stable one among other five amino acids with the average interacion energy-289.5 kJ/mol showing the highest charge transfers.Besides,hydrophobic side-chain had no significant influence on functionalization.In addition to Asp,other amino acids were stable with zwitterionic conformations,and rendered to be the most stable one in glycine,valine and proline functionalization systems.The theoretical results provide a valuable theoretical reference for the selection of amino acids in the functionalization of carbon nanotubes.Simultaneously,it provides a plurality of drug deliveries for the drug delivery systems of natural derivative drugsThe drug delivery system of natural product-derived anti-influenza drug BA was constructed in this paper.Within the interaction of BA drug molecule with(5,5)SWCNT functionalized by amino acid,O site of BA drug molecule represented favorable reactivity,and zwitterionic BA generated stable complex with delivery system,therefore,the amino acid functionalization(5,5)SWCNT was the ideal drug delivery system for zwitterionic BA.Compared with the neutral conformation,zwitterionic amino acid was more conducive to stabilize neutral/zwitterionic BA drug molecule,therein,O_b1O system was the best interaction mode with the interaction energy-218.7 kJ/mol.Further researches on the amino acid functionalization(5,5)SWCNT and present anti-influenza drugs oseltamivir,zanamivir and peramivir were carried out,showing that the interaction mechanism was also applied to these drugs.As a result,the interaction mechanism has great universality,and the amino acid functionalization(5,5)SWCNT system has a good application prospect of natural products and their derivative anti-influenza drugs delivery.In summary,Gly functionalized Al/(5,5)SWCNT successfully by using various configurations in this paper,indicating that zwitterionic configuration was the most stable one among all configurations.It provides the possibility of delivering anti-influenza drug(zwitterionic drug molecule is active conformation).On this basis,the different effects of dopants and side chains on the functionalization efficiency were illustrated.Finally,the drug delivery system of anti-influenza drug molecule BA at the molecular level was constructed,indicating the interaction mechanism.Then the universality of the interaction mechanism was verified through the study of other anti-influenza drug delivery systems.The all above work provide the theoretical basis and scientific basis for the research of application for carbon nanotubes in the natural product derivative drugs,and promote the research and development of natural product derivative drug delivery system.