Theory Studies On The Inclusion Complexes Of Cyclic Decapeptide With 1-phenyl-1-propanol Enantiomers

Chiral discrimination is one of the most intriguing phenomena in chemistry. It is of great importance in analytic, organic, and biological chemistry. Particularly, studies on searching the desired host molecules dominate the scene. In recent years, cyclic peptides have been synthesized and used as anticancer, antimalarial, antibacterial and enzyme inhibition, which acts as host molecules to form inclusion complexes with some biological activities moelcules However, the interesting molecular recognition of cyclic peptides with guest compounds, still lacks theoretical study. Therefore, the study of the host-guest interactions between cyclopeptides and the enantiomers of a chiral molecule should provide a new insight into these interactions and elucidate chiral recognition processes in biological receptor molecules. Density functional theory (DFT) calculations have been carried out to study the mechanisms of two inclusion reactions in the paper.The first topic is "Density functional theory studies on the inclusion complexes of cyclic decapeptide with 1-phenyl-l-propanol isomers". Cyclic decapeptide (assigned as CDP), which was constructed with ten identical glycine units, are used as receptors that are capable of including the guest molecules inside the peptide cavity probably caused by the conformational flexibility and noncovalent interactions. 1-phenyl-l-propanol (PP) which can accelerate bile secretion, eliminate concretion and debase cholesterin is typical examples that are useful for constructing a simple and good model to study chiral discrimination. The separation of the enantiomers of 1-phenyl-l-propano has already been carried out in the experiment. However, the separation results are not desirable. In the present work, the inclusion complexes of cyclic decapeptide (CDP) with the 1-phenyl-1-propanol isomers (E-PP) firstly studied using the density functional theory (DFT) B3LYP method. Almost all possible locations of E-PP with CDP were taken into account to obtain the most stable conformation of inclusion complexes. The optimized structures and the binding energy (BE) indicate that the CDP/S-PP inclusion complex is much more stable than the CDP/R-PP one. The conformational characteristics of inclusion complexes show that the distinct differences for hydrogen bond interactions occur in the different inclusion complexes. The following NBO analyses confirm the occurrence of these intermolecular hydrogen bonds. Moreover, the MD results support the conclusions obtained by B3LYP/6-31+G(d,p). Additionally, the thermodynamic calculated results demonstrated that enthalpy changes (AH) are prominent in the inclusion processes. Take the solution effects into account, the entropy is still a favorable driving force for the formation of CDP/E-PP The observations in this work indicate that cyclic peptide is to be desirable host molecule for chiral and molecular recognition.Considering that polar group modified cyclopeptides also form complexes with the increase in solubility, we have performed a density functional theory (DFT) study of the interactions between polar groups modified cyclopeptides and PP enantiomers, which may have much theoretical and practical importance. In the present work, we investigate the inclusion complexes of carboxymethyl-cyclic decapeptide (CM-CDP) and D-amino-cyclic decapeptide (DA-CDP) with 1-phenyl-1-propanol (PP) isomers. The binding energy differences for the complexes indicate that modified CDP can form more stable complexes than native CDP.