Recognition of Aminated Guests by Acyclic Cucurbiturils in Biological Conditions

Abstract

The acyclic cucurbituril Motor2 has already been well documented in its binding to several types of molecular guests in phosphate buffer. However, while these tests provide a rough idea of motor2 affinity to different types of guests, they are incomplete in that they do not reflect how motor2 actually binds in body conditions. The human body contains many proteins and macromolecules that can affect the host-guest interactions of motor2, so it is important for new binding constants to be measured for motor2 in body conditions. In order to do this, Isothermal Titration Calorimetry (ITC) was used to measure motor2 binding constants to several different guest types in several different solutions, including albumin and fetal bovine serum. It was found that when tested with cyclic, monoaminated guests, motor2 binding affinity did not decrease significantly from phosphate to protein serum solvents. This retained affinity held across several different ring sizes and shapes. Motor2 binding affinity did suffer greatly in protein serum for guests that were linear, regardless of how many amines they had. The results also indicated that more hydrophobic guests do not bind as well to motor2 once albumin and other proteins ae introduced to solution, while hydrophilic, polar guests have better affinity retention. The ITC testing results indicated that motor2 binding in body conditions is heavily dependent on the shape of the guests it is binding to, and that motor2 would be most effective at its purpose in the human body if it was used to target cyclic amines and similar types.