Chemistry Reference
In-Depth Information
To obtain the results that are illustrated here, the MMX method of the PCModel
program was used to virtually build the complexes and execute a coarse geometry
optimization. More accurate geometry optimization was then carried out using the
Parameterization Model 6 (PM6) method of the MOPAC program. PM6 is a semiem-
pirical quantum mechanics method (Stewart 2007) parameterized for 70 elements.
Lacking more specific information, the species were analyzed with the environment
dielectric constant set equal to unity. Certain net atomic charges were calculated
for the analyzed complex. The total charge on system is the algebraic sum of the
calculated net charges. For analysis by MOPAC, the total charge was set so that the
analyzed organometallic complex is not going to be a radical.
How accurately does the obtained structure reflect that of the real one? We
suppose that the analyzed complex interacts with the active site of a receptor mol-
ecule by a
key-lock
mechanism. The organometallic complex is flexible, due to the
presence of coordinative bonds, even if the ligand is rigid. The geometry of the two
systems of atoms starts to change gradually when the “key” approaches the “lock”.
The final complementary shape of the two components in the key-lock system is the
complement of two
modified
geometries, not the geometry calculated prior to inter-
actions. Accordingly, in QSAR calculations, molecular descriptors that have values
poorly influenced by the 3D final shape of the analyzed complexes are very useful.
In cases in which the active site structure is known, an alternative approach would
be geometry optimization and calculation of descriptors for the effector molecule-
active site ensemble. Docking of the effector molecule in the active site can be done
manually using computer-generated structures (Murcia et al. 2006; Huey et al. 2007;
Weber et al. 2006; Tucinardi et al. 2007).
The descriptors were calculated here, for each complex, using the computer
programs MOPAC/PM6, PRoperty Evaluation by CLAss Variables
(PRECLAV)
(Tarko 2005), and DESCRIPT (Tarko 2008a). The LogP descriptor was calcu-
lated using the KowWin algorithm of EPISuite software (EPISuite
®
; Meylan and
Howard 1995). The type of chemical bonds was defined according to Table 4.1.
In order to explain the utilized methods, some structures that are not organome-
tallic complexes are presented next.
Figure 4.1 presents the structure of auranofin, a compound considered to have
anti-HIV potential (ChemIDplus/a). The type of chemical bonds is presented in a
TABLE 4.1
Conventional Type of Chemical Bonds According
to Value of Bond Order
Computed Bond Order
Type of Chemical Bond
< 0.10
Ionic
0.10 < B < 0.76
Coordinative
0.76 < B < 1.05
Single
1.05 < B < 1.85
Aromatic
1.85 < B < 2.50
Double
> 2.50
Triple
