| It is of great significance to increase the solubility of hydrophobic small molecules.For example,improving the solubility of drugs can solve erratic absorption and low oral bioavailability,have important sense in preparation development and clinical application of hydrophobic drugs.Generally,drug solubility can be enhanced by solubilizer,cyclodextrins and liposome.The complementary base pairing of deoxyribonucleic acid(DNA)depends on hydrogen-bonding and form a variety of complex secondary structure.Among them,adenine and thymine can form Watson-Crick and Hoogsteen hydrogen bonds,Thymine-like “face” is composed of amide bond.Theoretically,the small molecules with thymine like “face” can combine with adenine through hydrogen bond,and obtain structures and implement some functions.Most of the imide compounds contain thymine-like “face”,which has good photoelectric properties and are commonly used as solar photovoltaic materials,organic photosensitive charge generation materials and dyes,but further application is limited due to poor solubility.In this paper,we first used cyanuric acid(CA)and urea as models to prove that water-soluble small molecules with thymine-like “faces” can form hydrogen bonds with adenine.Then,we use pyromellitic diimide(PD)with two thymine-like “faces” as a model to prove that polyadenine [poly(A)] can improve the solubility of PD through supramolecular interaction.The chemistry and physical changes caused from by poly(A)-PD interactions were characterized by ultraviolet-visible spectrophotometry(UV-Vis)and polyacrylamide gel electrophoresis(PAGE).Objective: 1.Cyanuric acid(CA)and urea were used as water-soluble small molecules models to prove that the small water-soluble molecules with amide bond can form hydrogen bond with adenine.2.PD was used as a hydrophobic small molecules model to demonstrate that poly(A)can improve the solubility of small molecules with thymine-like “face” composed of amide bond by supramolecular interactions.Methods: 1.According to the changes of absorbance and structure of poly(A),supramolecular interactions of CA and urea with poly(A)was analyzed by UV-Vis,PAGE and atomic force microscope(AFM).2.Poly(A)was added into saturated PD solution,and the undissolved PD was filtered after incubation.Solubility of PD and the changes of poly(A)structure was analyzed by UV-Vis and PAGE.3.Synthetic Hairpin-15 A,in which a hairpin structure links two poly(A)segments,interacts with PD through two thymine-like “faces”.Investigate the supramolecular interactions of PD with Hairpin-15 A.4.Analyze the specificity of hydrogen bonding between adenine and PD through the influence of random sequence DNA on the solubility of PD.5.Explore the influence of number of 2'-deoxyadenosine 5'-monophosphate,(dAMP)on PD solubility though changing the concentration and sequence length of poly(A),and investigate the influence of p H,time and temperature on the increase of PD solubility.Results: 1.UV-Vis and PAGE results show that the water-soluble small molecule CA can facilitate the poly(A)to aggregate through hydrogen bond and produce hypochromic effect.The complex of CA-poly(A)reduces the mobility.The results of UV-Vis and AFM show that urea with similar structure to CA can aggregate poly(A)through hydrogen bond and produce hypochromic effect.A large number of urea-poly(A)complex can be seen under AFM.2.UVVis and PAGE results confirm that the hydrophobic small molecule PD with amide bond can associate with hydrophilicity poly(A)through hydrogen bond,and the solubility of PD in aqueous solution is greatly increased,and they form PD-poly(A)complex.3.UV-Vis results show that Hairpin-15 A,connecting two poly(A)by DNA hairpin structure,can increase the solubility of PD,but,the effect of increasing solubility is weaker than single poly(A)chain due to its steric hindrance.In addition,the two thymine-like “face” of PD can combine on two poly(A)of Hairpin-15 A at the same time,and produce hypochromic effect.4.UV-Vis results show that the solubility of PD in aqueous solution could not be increased by random DNA sequence.PD specifically binds to adenine through hydrogen bond.5.UV-Vis results show that the number of dAMP was positively correlated with the solubility of PD.In addition,pH value of solution,incubation time and temperature all affect the solubility of PD.When pH = 7.0,incubation at 25?°C for 12 hours is the best condition to increase the solubility of PD.Conclusion: In this study,we propose a strategy to improve the solubility of hydrophobic molecules with amide bonds through supramolecular interaction.The water-soluble small molecules CA and urea can form super molecules with poly(A)through hydrogen bond,and the hydrophobic small molecule PD can combine with poly(A)through supermolecular interaction,which increases the solubility of hydrophobic small molecules in water.This strategy is expected to be used in other hydrophobic unnatural DNA analogues,such as pyrimidines,barbiturates and other small drug molecules containing thymine-like “face”,and it should allow us to more effectively control drug dissolution in future formulations. |
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