pH-Responsive Magnetism of Homoleptic Iron(II) Complexes
in Solution and Under Small Confinement
by René Nowak (03.09.2016)
This research investigates the possible application of iron(II) complexes as pH-responsive
contrast agent. The model system [Fe(bipy)3]2+ is naturally diamagnetic but can become
paramagnetic under formation of a protonated species which is introduced here. The underlying
mechanism has been elucidated with various methods, demonstrating that [Fe(bipy) 3]2+ can alter
relaxivity values due to its pH-responsive magnetism. Furthermore it is shown that those
properties can be preserved under small confinement in zeolites.
A plethora of iron(II) complexes is known which can exist in two different magnetic states.
The phenomenon known as spin-crossover (SCO) allows to switch such systems between the
diamagnetic low-spin state (LS, S = 0) and the paramagnetic high-spin state (HS, S = 2) [1].
Numerous external triggers like temperature, pressure, light, solvent molecules or even X-rays
are known and the transition can take place in mononuclear, 1-dimensional or network
structures [2]. Besides possible applications as sensors or storage devices they are promising
candidates as smart contrast agents [3]. In the HS state they reduce the longitudinal relaxation
time T1 of surrounding solvents while leaving it unchanged in the LS state; a feature
impossible to introduce to permanently paramagnetic lanthanides like Gd(III) [4]. Particularly
interesting are Fe(II) systems switchable by ion concentration, pH or other metabolic
parameters serving as prototypes for functional magnetic resonance imaging (fMRI) [5]. Aim
of this research is to study the pH-response of iron(II) complexes and [Fe(bipy)3]2+ is
introduced here in particular.
The results of magnetic measurements in solution (Fig. 1A) at different pH reveal a pHdependent magnetism of [Fe(bipy)3]2+. At 300 K, an increase of γHS with rising proton
concentration is observed. At pH 7 γHS is with 0.03 almost negligible while at pH 2 and pH 1
the solutions are clearly paramagnetic with γHS values between 0.14 and 0.27. This
corresponds to a pH-dependent spin state switch between a diamagnetic (S = 0; γHS = 0)
iron(II) LS species and a paramagnetic (S = 2; γHS = 1) iron(II) HS species. Additionally this
spin state switch in solution is temperature dependent. At pH 1 γHS varies between 0.21 and
0.46 while going from 260 K to 350 K. This change is completely reversible. The 1H-NMR
spectra at different pH (Fig. 1B) show at pH 6 the typical four signals for the protons of the
[Fe(bipy)3]2+ ion. When lowering the pH to 4, new signals are emerging in the aromatic
region that are associated with the appearance of a diamagnetic protonated species
[Fe(bipy)3H]3+.
Figure 1: Characterization of [Fe(bipy)3]2+ in solution. A: Plot of γHS versus T at different pH
values. B: pH-dependent 1H-NMR spectra of [Fe(bipy)3]Cl2 in D2O. C: Proposed mechanism
for the interaction of [Fe(bipy)3]2+ with protons.
A mechanism for the formation of a protonated diamagnetic and paramagnetic species
[Fe(bipy)3H]3+ is proposed (Fig. 1C) were a reversible bond break between the iron center and
the protonated nitrogen of the ligand is responsible for a proton-driven coordination-induced
spin state switch (PD-CISSS). This should increase dramatically the relaxivity of water.
Indeed is a strong pH dependence of ∆r1 observed in water. For [Fe(bipy)3]2+ ∆r1 is between
0.00 s-1mmol-1L (pH 7, LS, no coordination spot) and 0.18 s-1mmol-1L (pH 1, γHS = 0.27, free
coordination spot) – corresponding to an increase of the molar relaxivity by a factor of 18.
This serves as proof of principle that the described systems are prototypes for pH-responsive
contrast agents.
Furthermore it is possible to encapsulate the complex [Fe(bipy)3]2+ inside the voids of zeolite
NaY under preservation of the pH-responsive magnetism by exploiting interzeolitic Brønsted
acid sites. A reversible color change from red to colorless is triggered by heating/standing on
humid air similar to the bulk material in solution. This process is illustrated in Fig. 2 (middle).
Simultaneously is an increase of the mass magnetic susceptibility (mass) observed when
water is removed from the interzeolitic channels reducing the intrinsic pH (Fig. 2, right). The
preservation of the pH-responsive magnetism in the host material is important since zeolite
nanoparticles are biocompatible and specific forms are already approved as contrast agent [5].
Figure 2: Change of the optical and magnetic properties upon heating (solvent loss) of
[Fe(bipy)3]2+ encapsulated in zeolite NaY.
[1]
a) M. A. Halcrow, Spin-Crossover Materials, Wiley & Sons Ltd., Chinchester, 2013; b) P.
Gütlich, H. Goodwin, Spin Crossover in Transition Metal Compounds I-III, Springer
Berlin/Heidelberg, 2004.
[2]
R. Nowak, W. Bauer, T. Ossiander, B. Weber, Eur. J. Inorg. Chem. 2013, 975-983.
[3]
a) S. Venkataramani, R. Herges, Science 2011, 331, 445; b) R. Herges, Nachr. Chem. 2011,
59, 817-821.
[4]
a) F. Touti, J. Hasserodt, Inorg. Chem. 2012, 51, 31-33; b) V. Stavila, J. Hasserodt, New J.
Chem. 2008, 32, 428-435.
[5]
A. E. Merbach, L. Helm, E. Tóth, The Chemistry of Contrast Agents in Medical Magnetic
Resonance Imaging, Wiley, Chinchester, 2013.