T. Huyen Vu, et al.
Journal of Inorganic Biochemistry 203 (2020) 110864
4
.2. Formation of the iron(III) complexes
Table 3
Coordination bond distance (Å) between iron(III) and the different chelating
sites for a selection of HQ-based complexes. Bond distances are optimized at
PCM-PBE0 level of theory with (+D3(bj)) or without (noCor) empirical dis-
4.2.1. Stoichiometry of the iron(III) complexes
Owing to their bidentate character, HQ and its both NHQ and OHQ
★
persion corrections with the 6-31+G basis set. Crystallographic structure
ester derivatives are expected to strongly chelate iron(III). One
parameters of the O-TRENSOX-based complex are reported as a matter of
equivalent of FeCl is added to a solution of HQ, and the absorption
3
comparison.
spectra are acquired first in formiate and then in acetate buffer (see
Table 2 and Fig. S2 in the SI). The Specfit analysis of the spectra shows
that in the presence of iron(III), the pKNH′ and pKOH′ values (Eqs. (1)
and (2), the prime factor exponent notation depicting the presence of
iron(III)) are decreased by around 1.9 and 5.3 units, respectively. It thus
Iron(III) complexes
Fe–O
Fe–N
Fe–O(=C)
noCor
+D3(bj)
noCor
+D3(bj)
noCor
+D3(bj)
a
[Fe(HQ) ]
3
1.973
1.970
1.970
1.937
1.974
1.977
1.970
1.931
2.181
2.307
2.168
–
2.185
2.274
2.184
–
–
–
3
+
a
a
demonstrates the complexation of Fe
by both acid-base sites of HQ.
[Fe(NHQ)
3
]
3
–
–
[
[
[
Fe(OHQ)
]
–
–
In the same experimental conditions, the pKNH′ of NHQ and OHQ de-
creases by 1.9 and 1.7 units, while the pKOH′ decrease is estimated to
a
Feoo(OHQ)
3
]
2.083
2.090
b
Fe(O-TRENSOX)]
1.940
–
–
2.034
4
.0 and 7.6, respectively. In case of OHQ, the larger pKOH′ variation
a
b
indicates the breaking of the 6-member intramolecular hydrogen-
bonded ring stabilizing the structure and the formation of a iron(III)
complex involving its 2 acid-base functions.
Computed at DFT level.
Crystallographic structure from Ref. [72].
The formation of the iron(III) complexes with HQ derivatives is
further confirmed by direct and reverse ITC titrations (see Fig. S3 in the
(NHQ)
3
] or [Fe(OHQ) ] complex show similarly that iron(III) is hexa-
3
coordinated by 3 NHQ or OHQ ligands, and lead to an energetically-
SI). At pH 2.0, the direct titration, i.e. the titration of HQ by FeCl ,
3
favored HS state configuration. Due to a larger steric hindrance, both
provides a stoichiometry of 0.4 ± 0.1 equivalents of iron(III) cation and
resulting complexes are more distorted than [Fe(HQ) ]. The Fe-O mean
3
3
an affinity constant of (2.8 ± 1.3)× 10 . The reverse titration agrees
distance is measured as 1.970 Å and is very similar to the one of [Fe
(HQ) ] (Table 3). However, the Fe–N mean distance is significantly
larger (shorter) for [Fe(NHQ) ] ([Fe(OHQ) ]) with respect to the one of
with the direct one and shows a metal cation chelated by (3.2 ± 0.3)
equivalents of HQ and an affinity constant merely equals to the pre-
3
3
3
3
vious one within the uncertainty limits, i.e. (2.1 ± 0.3)× 10 . As a
[Fe(HQ) ] and is estimated to be 2.307 (2.168) Å versus 2.181 Å. This
3
difference in structure impoverishes the spin density of Fe in the NHQ-
result, both titrations converge to the thermodynamically favored for-
mation of an iron(III) complex coordinated by 3 HQ molecules. More
precisely, the ITC analysis shows that at room temperature and acid pH,
based complex (4.7 versus 5.0 a.u.) and reinforces it to 5.2 a.u in case of
the OHQ-based one. Particularly for [Fe(NHQ) ], these deviations with
3
−
1
the reaction is endothermic (ΔH = 0.5 ± 0.1 kJ mol ) and driven by
entropy (TΔS > ΔH), i.e. that the water/HQ ligand exchanges increase
the entropy and drive the reaction to the formation of the complex. At
pH 7.4, the direct titration of HQ by ferric citrate confirms the ther-
modynamically favored hexa-coordination of iron(III) with 3 HQ mo-
lecules (n = 0.46 ± 0.15, see Fig. S3 in the SI). However, like pre-
viously observed for the catechol ligand [44], the reaction is found to
respect to the ideal octahedral environment of the metal may lead to
the formation of less stable complexes with respect to [Fe(HQ) ].
3
The OHQ ligand allows however to consider another chelation en-
vironment for iron(III) (Fig. 1). Indeed, the spatial proximity of the
carbonyl group and phenol-like hydroxyl function of this ligand allows
the formation of a less contrained 6-member ring between Fe and both
oxygen donor sites. The resulting complex is dubbed [Feoo(OHQ) ].
3
−
1
be exothermic (ΔH = −(53 ± 1) kJ mol ) in neutral medium. Thus, it
implies that the formation of the coordination bond between the ferric
cation and HQ is energetically more important than the decoordination
and release of water within the solution (|ΔH| > |TΔS|).
With this salicylate coordination, the complex adopts a quasi-ideal
octahedral geometry with a Fe–O mean distance estimated to 1.937 and
2
.083 Å for the hydroxyl and carbonyl sites, respectively (Table 3).
These findings agree with previous works reported by Serratrice and
coworkers. They first demonstrated the iron chelation by the carbonyl
group by IR spectroscopy, the carbonyl characteristic band being blue-
4
.2.2. Structure of the iron(III) complexes
3
+
shifted in presence of Fe [24]. They then confirmed this coordination
scheme by crystallizing the iron(III) complex by O-TRENSOX [72]. In
this specific case, the distance between the metal cation and the hy-
droxyl group is in perfect match (1.940 Å). Its distance with the car-
bonyl site is however 0.04 Å shorter (2.034 Å).
The iron(III) complex chelated by 3 HQ ligands can adopt 3 ground-
state electronic configurations, each one characterized by a different
population of the 3d orbitals of the metal by its 5 valence electrons. In
its low-, intermediate- or high-spin state (LS, IS or HS, respectively),
5
4
1
3
2
iron(III) adopts a (t2g) , (t2g
)
(e
g
) , or (t2g
)
(e ) electronic configura-
g
tion. A structure optimization of the neutral form of the complex [Fe
(
HQ)
3
] in its 3 allowed spin states demonstrates that the HS config-
4.2.3. UV/vis spectra of the iron(III) complexes
uration is by far the most stable state of the complex. PBE0 models the
The formation of the iron(III) complex by HQ-based ligands is now
analyzed by UV/vis absorption spectroscopy (Fig. 4). The addition of
−
1
HS state 10.0 (14.4) kcal mol more stable than the LS (IS) one. Even
if global hybrids are known to overstabilize the HS configuration [39-
FeCl to a solution of HQ at pH 2.0 leads to the appearance of 2 new
3
4
1,71], the OPBE semilocal approximation confirms the state ordering
absorption bands within the visible region (653 and 452 nm), and the
−
1
★
(
HS being 6.0 and 11.8 kcal mol
more stable than LS and IS, re-
persistence of the characteristic π → π band of the HQ ligand in acidic
spectively) and imposes the HS configuration as the most stable elec-
tronic state of the complex. Within the sextet spin state multiplicity, the
structure of the complex is slightly distorted with respect to an ideal
octahedral coordination due to the formation of a constrained 5-
member ring between Fe and the coordination sites of the ligand. In-
deed, the Fe-O and Fe-N mean distances are estimated to be 1.973 and
medium (369 nm) (Table 4). These UV/vis features are in line with
what observed experimentally for (8-hydroxyquinoline-5-sulfonic acid)
iron(III) and quinolobactine complexes [73-75]. The same experiment
performed at pH 7.4 leads to a slightly modified absorption spectrum
characterized by an absorbance decrease and blue shift of the first low-
lying band from 653 to 582 nm, followed by the persistence of both
others at 455 and 369 nm, respectively (Fig. 4). The spectrum presents
an isosbestic point in the visible region. This feature confirms the ITC
experiments (considering a one-third ratio equivalent of iron(III)) and is
the signature of the formation of a unique complex with a fixed stoe-
chiometry.
2
0
.181 Å, respectively (Table 3), with a spin density of about 5.0, 0.1 and
.0 a.u. localized on the Fe, O and N atoms, respectively. The addition
of the D3(bj) empirical dispersion correction does not modify the
structure of the complex and confirms the reliability of PBE0 with re-
spect to these systems.
Same computations performed on the neutral form of the [Fe
Computations performed at the TD-PBE0 level of theory on the acid
5