Molecular Simulation Of Graphene Water Channels And Their Drug Loading Function

Graphene and its derivatives have shown strong potential for nanotechnology applications in environmental science,biomedicine and biotechnology due to their unique atomic structure,physical and chemical properties.However,pristine graphene(PG)is nonpolar,chemically stable,insoluble in water,and difficult to react with other substances,while graphene oxide(GO),a derivative of graphene,has more unique physical and chemical properties due to the random distribution of polar oxygen-containing functional groups such as epoxy and hydroxyl groups on both sides of the carbon plane and the presence of carboxyl groups bonded at its edges,including good bio compatibility and amphiphilicity,etc.Therefore the structure and properties of graphene and graphene oxide have attracted much interest from researchers in the field of nanobiotechnology,and extensive studies have been carried out in molecular,ion sieving,drug delivery and bioimaging.Molecular dynamics simulations(MD)act as a bridge between macroscopic experiments and microscopic mechanisms,allowing not only the interpretation of experimental phenomena,but also theoretical analysis.As such,it is an effective aid to experimental studies,not only to observe molecular dynamics behaviour and structural features at the nanoscale,but also to obtain detailed information on the interactions between graphene and other media,including the conformational changes and interaction energies of the media,etc.In this thesis,computer simulations and analyses of the mechanisms involved were carried out to investigate the effects of graphene nanochannel spacing and oxidation on water permeation,the loading of the small molecule bortezomib(BOR)in graphene aqueous solution and its slow release mechanism to lipid membranes,and the adsorption stability and slow release rate of three drugs on graphene surfaces,respectively.Firstly this study transposes the excellent functionality and performance of water channel proteins in biology by mimicking their key structures and mass transfer mechanisms into bionanographed graphene nanochannels.In this work,we explored the effects of interlayer spacing and the degree of oxidation on the transport of water through graphene nanochannels.The results show that GO has a strong adsorption capacity.the adsorbed layers of water molecules on the GO surface are thermodynamically stable and do not flow easily.When the interlayer spacing was in the range of 0.6～1.0 nm,water molecules formed a single or double adsorption layer between the two GO nanosheets.When the interlayer spacing is greater than 1.2 nm,the other water layers in the middle of the nanochannel become disordered.Considering the separation performance based on size exclusion,the most suitable interlayer spacing for water nanofiltration is 1.2 nm,where there is a layer of mobile water molecules.The oxygen-containing groups are not conducive to water permeation,and as the degree of oxidation increases,more and more hydrogen bonds prevent water from flowing across the GO surface.Our simulation results may help to improve the design of GO nanofiltration membranes for water treatment.Secondly,graphene has been considered as one of the most promising candidates for drug delivery to target cells due to its large surface area and high cellular uptake rate.In this work,we performed molecular dynamics simulations to investigate the potential application of graphene as a substrate to carry and deliver drug molecules.Bortezomib(BOR)was chosen as a model drug due to its atomic structure and polarity suitable for adsorption onto PG and GO.In this,the BOR molecules were first loaded onto the PG surface to form PG-BOR complexes.Simulations revealed that these complexes readily entered the lipid bilayer and finally BOR was slowly released from the PG surface into the membrane.the entry of PG-BOR complexes into the membrane was mainly driven by hydrophobic interactions between the lipid tails and the nanosheet base surface.In contrast,electrostatic interactions between the polar groups of BOR and the lipid head groups contribute to the release of BOR from PG into the membrane.Unlike PG,BOR is difficult to be removed from the GO surface after the GO-BOR complex enters the lipid bilayer.This is because the electrostatic attraction of the oxygen-containing groups enhances the binding of BOR to GO.the free energy of BOR adsorbed on GO is lower than that on the surface of PG.Mean force potential(PMF)calculations show that the adsorption strength and retardation rate of graphene nanosheets can be tuned by oxidation and surface electrochemical modifications.Finally,to continue to investigate in depth the ability of graphene in drug delivery.We added two model drugs,Pyrimidine(PRI)and Pregabalin(PRE),to the previous work.The results showed that GO’s adsorbed much more strongly to the three drugs than PG,as confirmed by the previous work.Compared to PRE and BOR,PRI molecules are more suitable for simultaneous loading and release by PG and GO.The results of the above two simulations suggest that it is theoretically feasible to use graphene as a substrate for the delivery of specific drugs.