108
dination (Neilands 1995). Table 7.2 illustrates the structural representation of ironsiderophore complex among different classes of siderophore.
The physico-chemical parameter, i.e. pKa values of binding groups, has a great
influence on the siderophore’s complex stability as the oxygen atom in these complexes is interacting in a non-protonated state. From the available literature,
hydroxamic acid has been shown to have pKa values in the range of 8–10; however,
acetohydroxamic acid (main compound for monohydroxamate ligand) has shown to
have 9.29 pKa value. The pKa values of carboxylates lie in the range of 3.5–5 which
contributes to efficient iron imbibitions by carboxylate siderophores under low-pH
conditions. The microbes living in acidic medium (such as fungi) use carboxylate
siderophores for iron immobilization. In spite of this fact, the carboxylate siderophores couldn’t compete with stronger siderophores such as hydroxamates and catecholates as they are fully protonated at physiological pH. In catecholate, a model
monomer has been synthesized in such a way that once nitro group is added on para
position, then the pKa values of resulting alcohol groups were found to be 6.69 and
10.83. On the other hand, after substituting it with hydrogen atom, the resulting pKa
values were 9.26 and 13.3. The pKa values of binding groups have an impact on the
affectivity of siderophores as the oxygen atoms only bind with the groups in nonprotonated state. These values are not easily accessible and effected by side chain
modifications (Neilands 1995). The pKa values for hydroxamate, catecholate and
carboxamate groups exhibit the partly deprotonated states in the presence of iron at
neutral pH. Proton-independent pKa values do not demonstrate the actual ironbinding efficiency of siderophores at physiological pH due to incomplete deprotonation. For better analysis, pH analogous to pFe values is considered to be a better
approach for comparing the true relative abilities of iron binding with different siderophores by giving negative decadic logarithm of free iron concentration. As per
standards, the total ferric concentration and total ligand concentration are considered to be 10
−6
M and 10
−5
, respectively. The chelation efficiency is strongly influenced by pH of medium; thus, pFe value is a pH-dependent value. For instance, at
serum pH (i.e. 7.4), in the presence of enterobactin and aerobactin, the concentration of free iron is observed to have different pFe values which are 35.5 and 23.4,
respectively (Wilson et al. 2016; Miethke and Marahiel 2007).
Phytosiderophores are hexadentate ligands that coordinate with Fe
3+
from all six
coordination sites which explore a variety of combinations at the three binding sites
to form a potential iron-siderophore complex. In the contrary, many siderophores
use only one type of binding site to form the stable complexes with iron such as trihydroxamate siderophore (ferrioxamine) and tri-catecholate siderophores (enterobactin) (Renshaw et al. 2002).
7.7 Metal Ion Complex Formation with Siderophore
Several fungal species have been investigated with complex regulatory arrangements during intake of secondary metabolites, namely, mycotoxins (produced by
mycotoxigenic fungi) and its detoxification process of converting these metabolites
S. Bhardwaj et al.
dination (Neilands 1995). Table 7.2 illustrates the structural representation of ironsiderophore complex among different classes of siderophore.
The physico-chemical parameter, i.e. pKa values of binding groups, has a great
influence on the siderophore’s complex stability as the oxygen atom in these complexes is interacting in a non-protonated state. From the available literature,
hydroxamic acid has been shown to have pKa values in the range of 8–10; however,
acetohydroxamic acid (main compound for monohydroxamate ligand) has shown to
have 9.29 pKa value. The pKa values of carboxylates lie in the range of 3.5–5 which
contributes to efficient iron imbibitions by carboxylate siderophores under low-pH
conditions. The microbes living in acidic medium (such as fungi) use carboxylate
siderophores for iron immobilization. In spite of this fact, the carboxylate siderophores couldn’t compete with stronger siderophores such as hydroxamates and catecholates as they are fully protonated at physiological pH. In catecholate, a model
monomer has been synthesized in such a way that once nitro group is added on para
position, then the pKa values of resulting alcohol groups were found to be 6.69 and
10.83. On the other hand, after substituting it with hydrogen atom, the resulting pKa
values were 9.26 and 13.3. The pKa values of binding groups have an impact on the
affectivity of siderophores as the oxygen atoms only bind with the groups in nonprotonated state. These values are not easily accessible and effected by side chain
modifications (Neilands 1995). The pKa values for hydroxamate, catecholate and
carboxamate groups exhibit the partly deprotonated states in the presence of iron at
neutral pH. Proton-independent pKa values do not demonstrate the actual ironbinding efficiency of siderophores at physiological pH due to incomplete deprotonation. For better analysis, pH analogous to pFe values is considered to be a better
approach for comparing the true relative abilities of iron binding with different siderophores by giving negative decadic logarithm of free iron concentration. As per
standards, the total ferric concentration and total ligand concentration are considered to be 10
−6
M and 10
−5
, respectively. The chelation efficiency is strongly influenced by pH of medium; thus, pFe value is a pH-dependent value. For instance, at
serum pH (i.e. 7.4), in the presence of enterobactin and aerobactin, the concentration of free iron is observed to have different pFe values which are 35.5 and 23.4,
respectively (Wilson et al. 2016; Miethke and Marahiel 2007).
Phytosiderophores are hexadentate ligands that coordinate with Fe
3+
from all six
coordination sites which explore a variety of combinations at the three binding sites
to form a potential iron-siderophore complex. In the contrary, many siderophores
use only one type of binding site to form the stable complexes with iron such as trihydroxamate siderophore (ferrioxamine) and tri-catecholate siderophores (enterobactin) (Renshaw et al. 2002).
7.7 Metal Ion Complex Formation with Siderophore
Several fungal species have been investigated with complex regulatory arrangements during intake of secondary metabolites, namely, mycotoxins (produced by
mycotoxigenic fungi) and its detoxification process of converting these metabolites
S. Bhardwaj et al.