Density Functional Theory Calculations of Proton Affinities for Simple Organic Compounds and Drug-Like Molecules [SAME Research Program]Density Functional Theory Calculations of Proton Affinities for Simple Organic Compounds and Drug-Like Molecules [SAME Research Program]

IMG-20140107-WA0017by: Jutti Levita (a), Johannes Reynisson (b)

(a) Faculty of Pharmacy Universitas Padjadjaran Bandung 45363, Indonesia (E-mail:;

(b) School of Chemical Sciences Faculty of Science, the University of Auckland Grafton Campus building 529-305a 2-6 Park Avenue Auckland, New Zealand




Protonation reactions are important in chemistry and biology. Protonation and deprotonation are the first steps in many enzymatic reactions. Proton affinity, the negative of enthalpy change at standard conditions, is defined as the energy released when a proton is added to a system [1,2]. Experimental determination of these parameters showed that it was difficult or impossible due to many factors, e.g when the molecule is unstable or protonation undergoes fast reaction or other proton transfer reaction occurs [3]. Previous studies performed to predict proton affinity of volatile organic compounds by computational method comparison between ab initio and density functional theory methods. This study concluded that density functional theory approach showed better correlation with experimental values [2]. In the present research, we calculated proton affinities of sixty eight organic compounds and twenty five drug-like molecules using density functional theory (DFT) and compared with NIST data. Density functional theory B3LYP/6-31+G(d,p) was applied to optimize geometry and calculate the frequencies, total electronics, and zero point vibrational energies of the compounds, followed by B3LYP/6-311+G(2df,p) to calculate their energies. Of those, fifty two organic compounds (76.5%) and nineteen drug-like molecules (76%) showed excellent correlation.

Keywords: density functional theory calculations, proton affinity, protonation

Link for full article: SAME article-Jutti

This article was conducted from the SAME research program by Dr. Jutti Levita at the University of Auckland New Zealand 2013


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