MOL ECULAR PR OPERTIES O PTIMIZATION PROJECT 
That hydrogen bonding plays an important role in chemical processes, including enzymatic catalysis, is well known. This observation has inspired many approaches to take such interactions into account in QSAR and molecular modeling investigations. Up to now, the number of atoms that can participate in Hbonding has been used most often as the simplest descriptor of this interaction . Of course, such indicator variables are primitive, and do not reflect the influence of substituents near Hbond acceptors or donors.
On the basis of their own experimental measurements and published thermodynamic data on hydrogen bonding, Raevsky et al found that Hbond strength depends on the nature of substituents near the atoms that participate in bond formation [1,2]. The enthalpy values in measured Hbond complexes cover a wide range; they vary from 0.9 to 15.9 kcal/mol for "OH…O"; from 0.1 to 19.1 kcal/mol for "OH…N"; from 0.5 to 10.5 kcal/mol for "NH…O", and from 0.5 to 11.5 kcal for "NH…N".
Using a multiplicative approach to describe experimental thermodynamic parameters for about 14 thousand Hbond complexes, Raevsky et al. [35]: created uniform enthalpy (DH) and free energy (DG) Hbond scales:
D H = k_{1}(kcal/mol)E_{a}E_{d} (1)
D G = k_{2}(kcal/mol)C_{a}C_{d}+ k3(kcal/mol) (2)
where E_{a} is the enthalpy acceptor factor , E_{d} is the enthalpy donor factor , C_{a} is the free energy acceptor factor, and C_{d} is the free energy donor factor. Later Raevsky proposed also overall Hbond acceptor scale based on correlation of experimental property values with free energy acceptor factors to estimate an ability of different weak neutral and ionized acceptor atoms. Hbond factors can quantitatively characterize the acceptor or donor strength of any atom in any molecule.
Large data bases for these factor values as well as a program to estimate such values for atoms in organic molecules are contained in the program HYBOT (HYdrogen BOnd Thermodynamics) for Windows 95/98/2000/NT or for UNIX or for LINUX [6]. Besides HYBOT also calculates descriptors connected with steric and electrostatic interactions. Fig. below presents the results of calculation of molecular and atomic descriptors by means of HYBOT (version 2.3, 2003).
NN 
Desriptor 
Symbol 
1 
Molecular
polarizability 
α 
2 
Maximal
positive atomic charge in a molecule 
Max
Q+ 
3 
Maximal
negative atomic charge in a molecule 
Max
Q 
4 
Maximal
enthalpy Hbond acceptor
factor 
Max
Ea 
5 
Maximal
enthalpy Hbond donor factor 
Max
Ed 
6 
Maximal
free energy Hbond acceptor
factor 
Max
Ca 
7 
Maximal
free energy Hbond donor
factor 
Max
Cd 
8 
Maximal
overall Hbond acceptor
factor 
Max
Ca(o) 

Sum
of all positive atomic charges in a molecule 
ΣQ+ 
10 
Sum
of all negative atomic charges in a molecule 
ΣQ 
11 
Sum
of absolute values for all atomic charhes 
ΣQ 
12 
Sum
of all enthalpy Hbond acceptor factors 
ΣEa 
13 
Sum
of all free energy Hbond acceptor factors 
ΣCa 
14 
Sum
of all overall Hbond acceptor factors 
ΣCa(o) 
15 
Sum
of all enthalpy Hbond donor factors 
ΣEd 
16 
Sum
of all free energy Hbond factors 
ΣCd 
17 
Sum
of absolute values of all enthalpy Hbond acceptor and donor factors 
ΣE 
18 
Sum
of absolute values of all free energy Hbond
acceptor and donor factors 
ΣC 
19 
Sum
of absolute values of all overall Hbond acceptor factors and all free
energy Hbond donor factors 
ΣCa(o)+ΣCd 
References: