Self-assembly And Applied Fundamental Research Involving Cucurbit[n]urils With Some N-heterocyclic Pesticides

Designing,synthesizing and assembling nano-pesticide according to the theory of molecular recognition will provide a new theory guidance and applications system in pesticide preparation,pesticide residue analysis and the environmental treatment.As a type of novel synthetic acceptor,cucurbit[n]uril(Q[n]) which has the unique structure with hydrophobic central cavity and hydrophilic carbonyl group portals,can selectively bind different guest molecules to form self-assembly host-guest complexes,capsules and supramolecular entities, Thus,cucurbit[n]uril could be used in many different fields,such as molecular recognition, molecular machine,host-guest chemistry and supramolecular chemistry.However,the study of cucurbit[n]urils as the pesticide carrier was not sufficient,few papers have been reported.In this paper,acute toxic experiment of cucurbit[7]uril(Q[7]) in mice was investigated as a safe pesticide carrier for further research and development.Self-assembling interaction of cucurbit[7]uril with purine and pyrimidine base compounds were studied in details by using different methods,and the experimental results revealed that Q[n]could be sued as plant virus inhibitor.Furthermore,choosing N-heterocyclic compounds as model pesticides, self-assembling interaction of these compounds with Q[n]s,particularly the improvement in solubility,stability and so on,were studied in details.Moreover,some new compounds based on 9-[2-(phosphonomethoxy)ethyl]adenine-bis(L- amino acid) esters were designed and synthesized,and their bioactivities against TMV measurement about these new compounds and their Q[n]-based host-guest complexes were also investigated.The content of the study are as follows:To provide toxicological foundation for the cucurbit[7]uril as a pesticide carrier,acute toxic experiment of cucurbit[7]uril in KM mice was investigated.The experimental results indicated that the toxicity of cucurbit[7]uril was very low and the compound could be used as a safe and nontoxic pesticide carrier.Self-assembling of cucurbit[7]uril with purine and pyrimidine base moieties were studied in details by ¹H NMR spectroscopy,electronic absorption spectroscopy(UV-Vis),fluorescence spectroscopy and high performance liquid chromatography(HPLC) analysis.The experimental results revealed that self-assembling inclusion complexes were formed between cucurbit[7]uril and purine base(Adenine, Adenosine,2',3'-o-isopropylideneadenosine) and pyrimidine base(Cytidine,Cytosine).The self-assembling interaction of these guest compounds with the host Q[7]was influenced up on the pH of the medium greatly.It proved that the formation of inclusion with guests was controlled through a combination of hydrogen bonding and hydrophobic interactions.In addition,HPLC method with Q[7]modified mobile phase was also introduced to explore the interactions of Q[7]with the purine base and pyrimidine base.Cytarabine(Ara-C) was an important cytidine derivative that was served as drug to cure acute leukaemia.Inclusion complexes between Ara-C and Q[7]in aqueous solution were investigated by UV-Vis spectroscopy and ¹H NMR technique.The results showed the formation of the host-guest self-assembling inclusion complexes of Ara-C with Q[7],the pyrimidine moiety of Ara-C was entrapped in the cavity of the host Q[7]and the D-ribose ring was likely located at the portal of cucurbit[7]uril.The interaction between the host and guest was influenced up on the pH of the medium,and led to the different inclusion modes. Furthermore,the inclusion complexes were prepared by saturation solution method and the structure of the solid complexes were also investigated.Moreover,stability of the host-guest inclusion complexe was investigated by initial uniform rate experiment.The experimental results revealed that complexation of Ara-C with Q[7]offers a major improvement in drug stability.Finally,Bioactivities against TMV measurement about Ara-C and its host-guest inclusion complexes were investigated.The results showed that Ara-C and its inclusion complexes had some inhibition against TMV at 500μg/mL in vivo,and complexation of Ara-C with Q[7]offers a major improvement of inhibition against TMV in vivo.Self-assembling interaction of cucurbit[n]urils with two novel compounds 9-[2-(phosphonometh oxy)ethyl]adenine-bis(L- phenylalanine) ester(FH-1) and 9-[2-(phosphonomethoxy) ethyl]adenine-bis(L-leucine) ester(FH-2) were studied in details by ¹H NMR technique,fluorescence and IR spectroscopy.Furthermore,bioactivity against TMV of these compounds was also tested.The experimental results revealed that:(1) the amino acid moieties of the compounds could be entrapped in the cavity of the host Q[n]s and the rest moiety was likely located at the portal area of Q[n].It proved that the formation of 1:1 or 2:1 host-guest inclusion complexes controlled by the concentration of the host Q[n]s.In addition,the formation of inclusion complexes between Q[7]with the target compounds was confirmed by IR spectroscopy,and showed the presence of inclusion complexes in solid state. (2) The experimental results revealed that FH-1 and FH-2 changed like-oil substance after 2～3 days,but the solid inclusion complexes remained power after 90 days.The phenomenon was explained that the information of solid inclusion complexes can prevent the compounds from sucking water.(4) Bioactivities against TMV measurement revealed that the compound FH-2 and its inclusion complexes had some inhibition against TMV at 500μg/mL in vivo.Based on the interactions between Q[n]s and thiabendazole,the sensitive spectrofluorimetry for the determination of thiabendazole in aqueous solution by using Q[n]as sensitizing reagent has been established.The results were as follows:(1) ¹H NMR technique studies showed that the thiazole ring of TBZ were entrapped in the cavity of the host and the benzimidazole ring was likely located at the outside Q[6]and TMeQ[6]cavity.On the contrary, the benzimidazole ring of TBZ were entrapped in the cavity of the Q[7]and the thiazole ring was likely located at the portal area of Q[7].It proved that the formation of a host-guest inclusion complex was controlled by a combination of the size fit and hydrophobic interactions. (2) UV absorption and fluorescence spectroscopy studies showed that TBZ with Q[6],Q[7] and TMeQ[6]infomed 1:1 inclusion complexes.The constant of the TBZ inclusion complexes was in the order of K_Q[6]-TBZ≈K_TMeQ[6]-TBZ＞K_Q[7]-TBZ,demonstrating the importance of the size fit between the host and the guest in the complexation process.(3) By using Q[n]as fluorescence enhance reagent,a sensitive spectrofluorimetry for the determination of TBZ in aqueous solution has been established.The experiment results showed that the method is simple,selective and sensitive.And the determination for TBZ in tap water,river water and mineral water gave satisfactory results.The influence of Q[7],TMeQ[6]and HMeQ[6]on the solubilization of some hydrophobic organic pesticides(Kinetin,6-benzyladenine and thiabendazole) were investigated by phase solubility studies.The results showed that three hydrophobic organic pesticides with Q[7], TMeQ[6]and HMeQ[6]infomed 1:1 inclusion complexes.The solubility of three hydrophobic organic pesticides was significantly increased,demonstrating the importance of the size fit and hydrophobic properties of the host and guest in the complexation process.The effects of pH and temperature on complex stability were also investigated.The solubility of kinetin as well as the stability constant of its complex with Q[7]were affected by the pH of the medium,but the interaction of the Q[7]-6-BA and Q[7]-TBZ systems was independent up on the pH of the medium.Thermodynamic parameters of the formation of these host-guest complexes were also determined,and it showed that the formation of the inclusion complexes between three pesticides and Q[7]was enthalpy controlled,suggesting that hydrophobic and Van der Waals interactions were the main driving forces.Moreover,the size of the cavity of cucurbituril played an important role in the association process.In addition,the effects of cucurbit[7]uril on the sorption behavior of kinetin on two soils have been studied by batch equilibration experiments.The results showed the presence of Q[7]in the solution has increased the sorption of kinetin on to soils.This phenomenon was due to the enhancement of kinetin solubility as a consequence of formation of water soluble inclusion compounds Q[7]-KT.