Study On Functional Assembly And Medicines Performance Of Cucurbiturils With Porphyrin Macrocycle Molecules

Cucurbiturils (Q[n])with hydrophilic exterior and hydrophobic internal cavity is akind of safe and low toxicity drug carriers which can form host-guest supramolecularassembling compounds with guest molecule drugs group by hydrophobic interaction.The properties of Q[n], such as solubility，chemical stability，bioavailability and releaserate would be improved markely by the formation of the assembling compounds. In thispaper, the assembly between host molecules Cucurbit[n]urils (Q[n], n=7and8) and fivephotosensitizers of photodynamic efficacy were investigated. The assembly compoundswere characterized via Fourier transform infrared (IR),1H nuclear magnetic resonance(1HNMR) and Scanning electron microscopy (SEM). The fluorescence quantum yield,oil-water partition coefficient and solubility of host and guest molecules before andafter the assembly process were discussed，respectively. It has a valuable significancefor porphyrin drug applications and photodynamic therapy in cancer photosensitizerefficient screening in the future. This paper content mainly includes:1. Study on assembly complexation behavior of Q[7,8] with tetraphenylporphyrinmolecules(TPP) was investigated by UV absorption spectroscopy andfluorescent spectra techniques. The results show that assembly interaction Q [7,8] withTPP has taken place and the assembly rate is about1:1respectively; The effect of pHvalue of solution on the assembly system stability is in the range of3.0-11.0; Thethermodynamic data shows that assembly process could occur spontaneously. Theorderliness is enhanced after the assembly interaction. The main driving force is theentropy change; According to the chemical shift variations of host-guest moleculesbefore and after the assembly process, the main model of the assembly complex inwhich the benzene ring and part of pyrrole ring of guest molecule TPP were encapsulated into the Q [7,8] cavity was speculated. The assembly of TPP with Q[7,8]significantly decreased the fluorescence quantum yield and Q[7]+TPP drop is greaterthan Q[8]+TPP. Compared with corresponding tetraphenyl porphyrin monomer, thesolubility and the oil-water partition coefficient of assembly compounds (Q[7,8]+TPP)are obviously improved about10.0-35.0times and up to7.0times, respectively. Thecumulative dissolution rate of two assembly compounds is similar in adult succusgastricus (pH=2.0) and artificial plasma (pH=7.4). The release rate of TPP is faster thanthe original drug TPP since the assembly compounds were formed. Q[7,8] for TPP hassignificant solubilization effect.2. UV spectroscopy technique was used to discuss the supramolecular assemblyinteraction of Q[7]、Q[8] with Zinc tetraphenylporphyrin (ZnTPP). Within5.0<pH<11.0range, the interaction of Q[7]、Q[8] with ZnTPP was observed, Formation assemblyratios were found to be approximately1:1for Q[7]+ZnTPP and Q[8]+ZnTPP systemsrespectively in the pH=7.0. The effect of temperature on the stability of the assemblysystems shows that Q [7,8]+ZnTPP assembly is relatively more stable than the Q[7,8]+TPP. The fluorescence quantum yields show that fluorescence quenching of Q[7,8]for ZnTPP is obviously than Q[7,8]+TPP. The solubility and the oil-water partitioncoefficient of Q[7,8]+ZnTPP were improved significantly. Drug release behavior ofZnTPP in vitro shows that Q[7,8] for ZnTPP has significant solubilization effect.3. Assembly ratios of Q[7] with copper phthalocyanine(CuPc), manganesephthalocyanine (MnPc) and iron phthalocyanine (FePc), respectively were determinedwith equimolar molar ratio method and continuous variation method. The values areapproximately1:2. The effect of pH environmental factor on the stability of theassemblies shows that MPcs can form assembly complexes with Q[7] in acidic, neutraland alkaline conditions respectively. In order to explore the host-guest interaction model,the assembly complexes of MPcs with Q[7] were characterized by UV、IR and SEM.The results show two Q[7] molecules cavity respectively included one metalphthalocyanine molecule,s benzene ring and part of pyrrole ring. The complexation ofQ[7] with MPcs significantly improved the fluorescence quantum yield, lipid solubility,solubility and release rate in vitro of MPcs. These improvements of performance have atheoretical guidance for the practical applications of anticancer photosensitizer in future.