Estimating the Energies of Interactions

There are many approaches to tlie energetics of intermolecular interactions (vide infra). Here we document some cases where thrombin inhibitors have been used to provide energy estimates. 

The reference inhibitors 8a have carbonyl oxygens at both R1/R2 and R3/R4 and bind with the lower carbonyl oxygen accepting a hydrogen bond from the -NH of Gly216 (as modeled) and the upper carbonyl oxygen in the P pocket 

A first inhibitor 8b was generated (in the bicyclic series) with R1 = H, R2 = H, 

There is a complementary way of looking at this problem. We may simply ask, does a water molecule prefer to bind here when no inhibitor is present. The answer seems to be No, which supports the above argument. 

Another inhibitor series has been used to estimate the value of P pocket interactions - the Boehringer Mannheim di aryl sulfonamides [39] (also reported by 3-Di-mensional Pharmaceuticals [40-43]) (Fig. 7.11). 

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From the gas phase scattering data we conclude that a plane wave state for the electron in liquid helium lies at positive energy relative to the vacuum level in agreement with Sommers electron injection experiment. We proceed now to a semiquantitative treatment of free electron states in liquids characterized by a positive scattering length, which will be used to estimate the energy of interaction of a free electron with liquid helium (18). 

Some di-isomers are more stable than the trani-isomers. Yamamoto and Tomoda [143] estimated the energies of bond interactions in 1,2-haloethenes and proposed... 

An analysis of the EPR spectra of the P4 -L-Q ion radical pairs [41] made it possible to estimate the energy of magnetic dipole-dipole interaction between the paramagnetic fragments P+ and Q in these particles and to calculate from this energy the mean distance RPq 10-12 A between P and Q fragments in the molecule of the kind, depicted in Fig. 8 (n = 2), in which the dicarboxy bridge... 

Once a value of Q and N are found that give a reliable estimate for this sum Swh, then it is only a matter of multiplying by -5 2 or — f kT to arrive at the energy of interaction Gwh(l) and Hamaker coefficient Awh(l) ... 

The interaction of adsorbed CO and adsorbed oxygen has also been studied to estimate the energy of activation for the oxidation of CO on Pt (111) surface. Two mechanisms have been proposed the Langmuir-Hinshelwood mechanism and the Eley-Rideal mechanism. In the Langmuir-Hinshelwood mechanism, the associatively adsorbed CO interacts with adsorbed oxygen. The activation energy for oxidation is calculated as 1.6 eV for the transition state geometry. 

Low molecular weight, liquid nitriles, such as acetonitrile, are in fact highly associated, forming mainly dimers with the nitrile groups in antiparallel alignment. The energy of interaction has been estimated in the order of 20-25 kJ/mol (5-6 kcal/mol), the forces involved being mainly electrostatic in nature. 

If only two-body dispersion forces operate, a rough estimate of the surface energy can be foimd by adding up die energies of interaction on contact. The energy of interaction per unit area at a distance I has the form... 

In this volume mainly the theoretical studies are presented, however also examples of experimental results are included and all the computational results are strongly related to experimental techniques. The most important topics considered in the recent studies on hydrogen bond are discussed in this volume, such problems as how to estimate the energy of intramolecular H-bonds, covalency of these interactions, the distant consequences of H-bond since in earlier studies usually only the X-H- Y H-bridge was analyzed (X-H is the proton-donating bond and Y is an acceptor), the differences between H-bond and van der Waals interactions from one side and covalent bonds from the other side, the use of the Bader theory to analyze different kinds of H-bonds, the influence of weak H-bonds upon structure and function of biological molecules, etc. There are also topics related to the experimental results crystal structures, infrared and NMR techniques and many others. 

The work of cohesion can be estimated using the microscopic theory of Hamaker and De Boer [10,11]. Their model is based on a simple summation of the dispersion interactions between the molecules contained in two semi-infinite volumes of condensed phases, separated by a gap of thickness h (Fig. I-10). The interaction energy per unit interfacial area between two phases, Umol, is equal to the energy of interaction of all molecules contained above the plane Ox within the infinitely long cylinder of unit cross-sectional area S with those contained within the entire volume below plane... 

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