The Synthesis And Properties Of Molecular Pockets Based On Cholic Acid

Bile acids are natural amphiphilic compounds that exist in most animals. They are popular building blocks for preparing various functional materials. More recently, they became attractive candidates in the construction of molecular umbrellas or called "molecular pockets", which can form hydrophobic cavities or hydrophilic cavities when the polarity of the surrounding solvent changes, and the potential applications including drug delivery vehicles, molecular containers and so on.A series of tri- and tetra-armed molecular pockets based on cholic acid have been synthesized via click chemistry, they have been fully characterized by modern spectroscopic methods such as infrared absorption spectrum (IR), nuclear magnetic resonance (NMR), mass and elemental analysis. These molecular pockets can form hydrophilic cavities in polar solvents and hydrophobic cavities in non-polar solvents due to the facial amphiphilicity of cholic acid, and the conformation will transform when the polarity of the micro-environment changes.The position of 1,2,3-triazole moieties have great influence on the properties of tri-armed molecular pockets based on cholic acid. With 1,2,3-triazole moieties at the beginning of the cholate arms, trimer 1 can bring Cu2+ and pyrene together into the hydrophobic cavity and result in more efficient fluorescence quenching of the entrapped pyrene, but it needs a more hydrophilic environment to form hydrophobic pocket. With 1,2,3-triazole groups attached at the end of the cholate arms, the coordination between the molecular pockets and Cu2+ is not so strong, and can’t cause efficient fluorescence quenching of the entrapped pyrene, the coordination between 1, 2,3-triazole groups and Cu2+ does not affect pyrene enter the hydrophobic cavities.A tri-armed molecular pockets trimer 1, which has three 1,2,3-triazole moieties at the beginning of the cholate arms, not only can form hydrophobic pockets to shelter one pyrene molecule in aqueous solutions, but also can coordinate with heavy metal ions and lead to fluorescence quenching of the entrapped pyrene.1μM of heavy metal ions can cause severe fluorescence quenching of pyrene, therefore trimer 1/pyrene can be used as promising chemosensor for heavy metal ions. In addition, the complexation of trimer 1/Zn2+ can imitate metallohydrolase to promote the hydrolysis of p-nitrophenyl acetate (PNPA), and the catalytic capacity is 103 fold larger than the background rate of PNPA spontaneous cleavage. Moreover, the experimental results revealed the complex’s catalytic process is similar to natural enzyme’s catalytic process and also follow Michaelis-Menten Equation.Electron paramagnetic resonance (EPR) was used to study the chelation of molecular pockets and Cu2+, the number of the arms of the molecular pockets and the position of the 1,2,3-triazole groups has a certain effect on the coordination between the molecular pockets and Cu2+. The three arms of trimer 1 can bind to one Cu2+, which locates at the top of the hydrophobic cavities of trimer 1 and is surrounded by three cholate arms. In tetra-armed molecular pockets, only three arms can coordinate with one Cu2+ simultaneously due to steric hindrance. When 1,2,3-triazole groups attached at the beginning of the arms, the coordination between the molecular pockets and Cu2+ is strong, otherwise, when 1,2,3-triazole groups attached at the end of the arms, the coordination between the molecular pockets and Cu2+ is loose.