Chemistry Reference
In-Depth Information
3
Properties of Metals
and Metal Ions Related
to QSAR Studies
3.1 PROPERTIES OF METALS AND METAL IONS AS
TOOLS IN QUANTITATIVE STRUCTURE-ACTIVITY
RELATIONSHIP (QSAR) STUDIES
A complex set of interrelationships involving physical, chemical, biological, and
pharmacological factors are involved when a metal ion interacts with a biological
system. Therefore, it is more important to characterize the metal-biological system
than to characterize the species in a simple chemical system. In a comprehensive
work, Walker et al. (2003) reviewed approximately 100 diverse contributions dating
from 1835 to 2003 to evaluate the relationships between about 20 physicochem-
ical properties of cations and their potential to produce toxic effects in different
organisms.
Data are presented in the form of ionic properties, surrogate metal ion charac-
teristics described to reflect metal-ligand binding tendencies, thermodynamic con-
siderations, and equilibrium constants of metal ions with a variety of inorganic and
organic ligands of biological significance. Some of these physicochemical character-
istics described in this review are atomic number (AN), atomic weight (AW), melting
point (m.p.), boiling point (b.p.), density (ρ), molar refractivity (MR), electric dipole
polarizability for ground-state atoms (α), atomic radius, atomic electron affinity (EA),
electronegativity (Χ, X
AR
, or X
m
), ionization energy (I), total ionization potential (ΣI
n
),
ionization potential differential (ΔIP), electrochemical potential, standard reduction-
oxidation potential or absolute value of the electrochemical potential between the ion
and its first stable reduced state (ΔE
o
), or standard reduction potential or standard elec-
trode potential (E
o
), first hydrolysis constant (|log KOH|), softness parameter (σ
P
; σ
A
;
σ
W
), stability constant of a metal ion with ethylenediamine-tetraacetic acid (EDTA)
and sulfate, heat of atomization of the elements (ΔH
atom
), enthalpy of formation of the
elements (ΔH
o
f
), enthalpy of fusion (ΔH
o
298
), enthalpy and Gibbs energy of hydration
(ΔH
o
h
; ΔG
o
h
), coordinate bond energy of halides (CBE F; CBE Cl; CBE Br; CBE I),
crystal lattice energy of the elements and lattice energy of metal inorganic compounds
(LE), enthalpy of formation of oxides and sulfides (ΔH
o
, ΔH
s
), ion charge (Z), ionic
potential (charge to radius ratio; Z/r), the ionic index (Z
2
/r), the covalent index
Xr
(
)
,
2
m
AN/ΔIP, log AN/ΔIP, and finally, ZX
m
.
Qualitative and, especially, quantitative correlation between toxicity and physico-
chemical properties of metal ions may be useful in predicting toxicity to biologically
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