Study On The Interactions Of Dopamine Hydrochloride With Several Small Drug Molecules

Dopamine（DA）is one of the important neurotransmitters,which mainly present in the central nervous system of human and other mammals.It plays an important role in the nervous activity,and can regulate many biological processes and manage various cognitive functions in the central nervous system,such as emotion,behavior,memory and learning.In addition,the abnormal DA concentration in biological fluids can be used as one of indicators in the diagnosis of neurological diseases,such as schizophrenia,Parkinson’s diseases and restless leg syndrome.Due to the important physiological functions and pharmacological properties,DA has been focused for cross-disciplinary research in medicine,biology and chemistry,and also has a hot area of research for intermolecular interactions.Intermolecular interaction is ubiquitous in nature,and plays an important role in chemistry,physics,biology and medicine.DA contains active groups and it is easy to interact with bioactive substances and the drug molecules in the body,which can affect the metabolic process of the organism.Therefore,the study of the interaction between DA and various substances is very important for the life sciences,and also provides some references for medicine researches.In this paper,we use dopamine hydrochloride（DH）instead of DA to study the interaction of DH with twelve small drug molecules（gabapentin,antipyrine,chloramphenicol,vitamin B6,nicotinic acid,3-pyridinemethanol,cytosine,adenine,theophylline,urea,inositol,glucose）,and explore the action types and sites from the molecular point of view.The main contents of this dissertation are given as follows:1.The cyclic voltammetry（CV）was used to investigate the interaction of gabapentin/antipyrine/chloramphenicol with DH in water and phosphate buffer solution（PBS）.The results of CV showed that the electroredox process of DH was inhibited by adding of them,and the higher the concentration is,the stronger the inhibition.We think that the reason may be the formation of hydrogen bonding between the hydroxyl hydrogen atom of DH and the three substances respectively.Meanwhile,we found that the pH value of solution has an effect on the electrochemical behavior of DH in the three systems.In addition,the interactions of gabapentin,antipyrine with DH were further analyzed by density functional theory（DFT）and atomic in molecules theory（AIM）.The calculation confirmed the existence of hydrogen bonding in the three systems,and the hydroxyl hydrogen atoms of DH is the main site of action.2.The interactions of vitamin B6,nicotinic acid,3-pyridinemethanol with DH were studied by CV,¹H NMR and quantum chemistry calculations.The CV results showed that the existence ofπ-πstacking interactions in above systems,while hydrogen bonding were found in the DH-3-pyridinemethanol system,and the solution pH also has an effect on the electrochemical behavior of DH in the three systems.Meanwhile,the ¹H NMR results confirmed thatπ-πstacking interactions existed in above systems.The DFT and AIM results confirmed that hydrogen bonding,π-πstacking interactions existed in the DH-vitamin B6,DH-nicotinic acid and DH-3-pyridinemethanol systems in aqueous solution,and the C-H···πinteraction found in DH-nicotinic acid/3-pyridinemethanol system.3.The interactions of cytosine and adenine with DH were studied by CV,¹H NMR and quantum chemistry calculation.The results showed that hydrogen bonding andπ-πstacking interactions existed in the two systems,furthermore the C-H···πinteraction also found in DH-cytosine system.In addition,we studied the interactions in DH-theophylline system by CV,DFT and AIM,the results confirmed the existence of hydrogen boning in the system,and the hydroxyl hydrogen atoms of DH are the main sites of action.In addition,the solution pH also has an effect on the electrochemical behavior of DH in the three systems.4.The CV,DFT and AIM were used to study the DH-urea and DH-inositol system.The results showed that hydrogen bonding existed in above systems and the hydroxyl hydrogen atom of DH is the main sites of action.In addition,the interaction between DH and glucose in H₂O and PBS was studied by CV method and hydrogen bonding also presented in the system.Moreover,the pH value of solution also has an effect on the electrochemical behavior of DH in the three systems.