Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2025 Apr 30.
Published in final edited form as: Physchem. 2023 Dec 25;4(1):25–42. doi: 10.3390/physchem4010003

X-ray and nuclear spectroscopies to reveal the element specific oxidation states and electronic spin states for nanoparticulated manganese cyanidoferrates and analogs

Hongxin Wang 1,*, Songping D Huang 2,*, Anthony T Young 3, Stephen P Cramer 1, Yoshitaka Yoda 4, Lei Li 5,†
PMCID: PMC12043228  NIHMSID: NIHMS2053388  PMID: 40309398

Abstract

In this publication, the potential non-gadolinium magnetic resonant imaging agent – the nanoparticulate K2Mn[Fe(CN)6], its comparison sample KFe[Co(CN)6], as well as their reference samples were measured and analyzed with Mn, Co and Fe L-edge X-ray absorption spectroscopy (L XAS). From the information obtained, we conclude that K2Mn[Fe (CN)6] has a high spin (hs)-Mn(II) and a low spin (ls)-Fe(II), while KFe[Co(CN)6] has a hs-Fe(II) and a ls-Co(III). In these Prussian blue (PB) analog structures, L XAS also concluded that the hs-Mn(II) in K2Mn[Fe(CN)6] or the hs-Fe(II) in KFe[Co(CN)6] is bonding to the N in the [M(CN)6]4−/3− ions [where M = Fe(II) or Co(III)], while the ls-Fe(II) in K2Mn[Fe(CN)6] or the ls-Co(III) in KFe[Co(CN)6] is bonding to the C in the [M(CN)6]4−/3− ion, suggesting the complexed metalloligand [Mn(II) or Fe(II)] occupy the N-bound site in PB. Then, nuclear resonant vibrational spectroscopy (NRVS) was used to confirm the results from the L XAS measurements: the Mn(II), Eu(III), Gd(III), Fe(II) cations complexed by [M(CN)6]n−-metalloligand are all taking the N-bound site in the PB-like structures. Our NRVS studies also approve that iron in K2Mn[Fe(CN)6] compound has 2+ oxidation state and is surrounding by the C donor atoms in the [M(CN)6]n− ions.

Keywords: nanoparticulate manganese cyanoferrates, non-gadolinium magnetic resonant imaging agents, L-edge X-ray absorption spectroscopy, L XAS, nuclear resonant vibrational spectroscopy, NRVS, oxidation states, electronic spin states

1. Introduction

Magnetic resonance imaging (MRI) has emerged as a prominent non-invasive and nonradioactive tool for diagnosing various diseases and/or testing human organ functions [1, 2]. To aid the diagnoses, it is often necessary to administer an imaging agent to improve the contrast [1, 3]. This is especially true for imaging the brain or spine where small details are often pursued [4]. For example, Figure 1(a) illustrates the use of a contrast agent for the MRI of the brain. Specifically, the right-sided Figure 1(a) shows a much clearer and more detailed picture with the use of a contrast agent in comparison with the one on the left where no contrast agent is used. The current clinical MRI agents all contain a single paramagnetic metal ion in their centre, with gadolinium (Gd) is the most frequently used metal so far in the commercial contrast agents. e.g., Gd-DTPA (Magnevist®, Schering AG, Germany). These Gd based agents are used in about 1 in 3 of MRI scans to improve the clarity of the images for the internal structures of the human body [4–6]. Often, use of an MRI contrast agent improves the visibility of inflammation, tumours, and blood vessels, or, in some cases, even blood flow or the real time function of blood vessels. In turn, a better MRI image provides a better medical diagnostic accuracy. For example, many detailed heart or brain abnormalities can well be assessed [4, 6].

Figure 1.

Figure 1.

Open in a new tab

(a) The illustrative MRI images without (left) vs. with (right) a contrast agent; (b) the skin surface and its microscopic profile of NFS; (c) illustrative K- and L-edge X-ray absorption spectroscopy (XAS) transitions and the associated energy levels; (d) nuclear resonant vibrational spectroscopy (NRVS) transitions which measures the vibrations indirectly but with many advantages; (e) infrared absorption spectroscopy (IR), which measures vibrations directly.

Although Gd contrast agents have proven to be invaluable, they are not without drawbacks. In extreme cases, these agents can lead to a serious disease called nephrogenic systemic fibrosis (NSF) [6–11]. An example of NFS patients’ skin appearance as well as the detailed looking are shown as in Figure 1(b) and its right insert. These are the Gd-related deposits. In 2010, synchrotron radiation (SR)-based X-ray fluorescence microscopy (SXRF) and extended X-ray absorption fine structure spectroscopy (EXAFS) were used to chemically and spectroscopically characterize the Gd deposits in the skin from an NSF patient [8]. It has been concluded that the Gd deposits in that NSF case consist of a Gd-phosphate material with almost no Gd remaining coordinated to the original organic chelator [8]. One reason is that Gd3+ ion has a very similar radius with that of Ca2+ (i.e., 1.07 Å for Gd3+ and 1.02 Å for Ca2+) and can replace the Ca2+ in human body and skin [8]. Therefore, Gd-DTPA or other Gd-based agents are still considered harmful in general [6–9, 11–14], and hence safer alternative imagining contrast agents need to be explored.

From the entire periodic table, there are only a few elements that are considered suitable as MRI enhancement candidates. Specifically, they need to have a high number of unpaired electrons, a long electronic relaxation time, and a stable oxidation state under the physiological conditions inside the human body at the same time. Hence, the suitable candidates include, for example, Gd(III) (S=7/2), Eu(II) (S=7/2), Fe(III) (S=5/2), and Mn(II) (S=5/2). Among these, Mn(II) ion is a bio-essential element and thus more compatible with biological cells than Gd(III) is. It also has a high electronic spin (S=5/2) and a fast rate in water exchange, possessing almost ideal physical, chemical, and biological properties for MRI applications [15, 16]. These properties led to two U.S. Food and Drug Administration (FDA)-approved contrast agents for clinical use, i.e., MnDPDP (DPDP = dipyridoxyl diphosphate; Teslascan®) and MnCl2 (LumenHance®). However, all Mn complexes including MnDPDP are kinetically labile and susceptible to the interaction with other metals such as Zn, Cu and Fe, etc. In particular, Mn(II) from these agents can be released from the contrast agents to the human body to cause problems, e.g., to replace Zn(II) [17, 18]. MnCl2 in aqueous solution can exist as [Mn(H2O)6]2+ and Cl− ions in the stomach. Even in a strong HCl environment, it does not turn to form the suspected [MnCln](n−2)− complexes, which is very different from CuCl or AgCl. Although Mn(II) has much less toxicity than Gd(III), absorption of excessive amount of Mn can still cause neurotoxicity. Other single metal centred coordination complexes also show various disadvantages and various potential toxic concerns.

These concerns may be addressed by incorporating Mn (or other proper metal ions including Gd) into the Prussian blue (PB) structure in the form of nanomaterials [19, 20]. PB has an extremely high formation constants (e.g., Kf = 1.6×1031 for PB vs. 1023 for Gd-DTPA) and therefore is much safer for medical use. For example, it is one of the most important medications on the World Health Organization’s List of Essential Medicines [21]. In general, it has a chemical formula of FeIII4[FeII (CN)6]3·xH2O, with a structure shown in the Figure 1(b) in [22]. For an easier reference, we copied it as Figure S1 in the Supporting Information (SI). A quarter of Fe(II) centres along with CN− ions have to be absent from the crystal lattice in order to maintain a ratio of Fe(III):[FeII(CN)6]4− = 4:3 to realize the electrical neutrality of PB [23]. This arrangement creates void inside the structure that is filled by a varying number of H2O molecules (i.e., x = 1 to 12). For PB–like analogs such as the manganese cyanidoferrates K2Mn[Fe(CN)6] to be explored in this study, Mn:Fe=1 is maintained instead, while a counterion of K+, or sometimes other monovalent ions, such as Li+, Na+, K+ Rb+, Cs+, Tl+, or (NH4)+, can be used to maintain the electrical neutrality for the whole compound.

These PB–like compounds, e.g. K2Mn[Fe(CN)6], have attracted a great deal of attention as potential MRI contrast agents in the past ten years [19, 20] [24] because: 1) the extremely high formation constant leads to an extremely stable complex [19, 20]. This in turn contributes to a much reduced risk of exposing the patients to the metal ions; 2) these complexes have a long blood circulation time, which is desirable for detailed imaging studies [25]; and 3) a given nanoparticle can form a superparamagnetic domain. Such material can thus possess a much higher magnetic susceptibility as compared with the paramagnetic materials composed of single molecules. This property can produce a much higher MRI sensitivity. On the other hand, nanoparticles are still small enough to be freely transported inside the human bloodstream.

There are a few major scientific issues concerning K2Mn[Fe(CN)6] in general: 1) what are the oxidation states of the two metals inside the complex?, i.e. whether this complex has a Mn(II)/Fe(II), a Mn(II)/Fe(III), a Mn(III)/Fe(II) or a Mn(III)/Fe(III); 2) what are the electronic spin states (i.e., ls vs. hs, where ls = low spin and hs = high spin) of the two metal sites? 3) in PB, the ls-Fe(II) is taking the C-bound position in the [Fe(CN)6]4− ion and the hs-Fe(III) is taking the N bound position to the [Fe(CN)6]4− ion. In K2Mn[Fe(CN)6], whether the Mn takes the positions for the original N-bound hs-Fe(III) sites or those for the C-bound ls-Fe(II) sites in comparison with PB in Figure S1? For such simple complex, the chemical intuition seems able to suggest that the tightly bound [Fe(CN)6]4− ions from the starting material of K4[Fe(CN)6] will remain its original Fe(II) (S=0), while the complexed Mn can take PB’s hs-Fe(III) position and in principle be in different oxidation states [e.g., Mn(III) vs. Mn(II)] and/or different spin states (hs vs. ls) according to the Mn source. As the C-bound ls-Fe(II) in [Fe(CN)6]4− ion has an S=0, the total spin in such PB-like complex has the electronic spin of the N-bound metal alone – for instance, from the hs-Mn(II), S=5/2. Nevertheless, it appears to be very meaningful to use modern spectroscopies [26–35] to shed some lights directly on these issues which are also critical for evaluating its suitability as an MRI agent [19, 20].

SR-based X-ray absorption spectroscopy [abbreviated as XAS hereafters, Figure 1(c)] measures the electronic transition from a core shell to a valence shell. As XAS is sensitive to valence electrons and it is element-specific (related to core shell) at the same time, it is one of the best methods to investigate the oxidation state of a specific element in different chemical compounds or enzymes [27, 29–32, 36, 37]. For the 3d transition metal ions (e.g., Mn, Co or Fe ion), K-edge XAS uses a hard X-ray beam of > 4000 eV to study the transitions of 1s → 3d, → 4p and → continuum [Figure 1(c), the transition designated by the dashed blue line]. Although the information obtained from the K-edge XAS seems comprehensive [27, 32–34, 37], L-edge XAS [29–31, 36, 38, 39] [Figure 1(c), the transition designated by the solid red line] as well as L-edge RIXS or L-edge X-ray emission spectroscopy[40–43] have several advantages over the K-edge XAS for studying electronic structures such as oxidation states and spin states. These advantages include a direct probe of the ligand-metal bonding orbital (3d); a dipole-allowed 2p → 3d transition (vs. 1s → 3d in K-edge XAS); a better energy resolution (e.g. 0.1 eV vs. 1 eV); and a rich spectral multiplet which is specific to particular electronic structures and coordination environments [29–31, 36, 38, 39].

Nuclear resonant vibrational spectroscopy (or NRVS for short) is another SR-based modern spectroscopic technique that was widely used by physicists, chemists, biochemists, and materials scientists. It measures the phonons, or, in other words, vibrational modes associated with the nuclear transition for a specific isotope, as illustrated in Figure 1(d). The most frequently used NRVS to date is the 57Fe NRVS which has a nuclear resonant transition at 14.4 keV [28, 44–49]. In short, it is a scattering spectroscopy in general and a nuclear resonant scattering spectroscopy in particular. In comparison with the conventional infrared absorption spectroscopy (IR) [50, 51] [Figure 1(e)], it measures vibrations indirectly but has several distinct advantages. The most prominent advantages include but not limited to being isotope (e.g., 57Fe) specific for studying complicated systems [28, 48, 49, 52–55], having an almost zero background [28, 48], and being able to obtain a theoretically calculable partial vibrational density of state (PVDOS) [28, 45–47, 56]. These advantages make it a better method in comparison with the laboratory-based IR [28] [50, 51], Raman [28] and laser induced fluorescence (LIF) spectroscopies [57–59] as well as SR-based inelastic X-ray scattering (IXS) [28] [60]. This modern spectroscopy became available in mid 1990s due to the development of the third-generation SR sources which provides the strong X-ray pulses with specific timing structure, advanced X-ray optics which lead to a monochromator with an 1 meV energy resolution to measure vibrations, and modern detectors which extract weak nuclear scattering signal from the huge electronic scattering counts in the time domain, and in turn, it has pushed a great advancement in physics, chemistry, biochemistry and materials science, etc. for the past 28 years [45–49, 55]. In chemistry and bioinorganic chemistry, for example, this technique has uncovered Fe-S/P/Cl, Fe-CO/CN/NO and Fe-H/D vibrational modes inside various inorganic complexes as well as dilute iron enzymes [28, 61–64], and thus become an excellent pinpointing tool to study iron-specific electronic and structural properties, including iron oxidation state(s) and coordination environment. For PB–like compounds, it can pinpoint to the features attributable to the N-blund hs-Fe(III) or those to the C-bound ls-Fe(II) [22, 28].

In this publication, the K2Mn[Fe(CN)6] complex was first measured and analyzed with the Mn and Fe L-edge XAS. For comparison, KFe[Co(CN)6] as well as their reference samples (K4[Fe(CN)6] and K3[Co(CN)6]) were also measured and analyzed with the Fe and Co L-edge XAS. From the information obtained from these L-edge XAS measurements, in reference to Figure S1, K2Mn[Fe(CN)6] is confirmed to have a hs-Mn(II) bound to the [Fe(CN)6]4− ion in the N position in 6CN− and a ls-Fe(II) bound to the 6CN− in the C position. In comparison, KFe[Co(CN)6] has a hs-Fe(II) bound to the in the N position and a ls-Co(III) bound to the C position. For NRVS, 57Fe labelled (NH4)2Mg[57Fe(CN)6] and K57Fe[Co(CN)6] were first presented as the two standards to illustrate the nature of the two “peaks” in the natural PB NRVS [22]. Then, non-labelled K2Mn[Fe(CN)6] was measured with regional NRVS where only the energy regions around the resonant peak and the Fe-CN vibrational peak were measured [22, 28]. For discussion, the previously measured regional spectra for KGd[Fe(CN)6] [65] and KEu[Fe(CN)6] [22] are also cited and compared with K2Mn[Fe(CN)6]. NRVS concluded that the nanoparticulated manganese cyanidoferrates K2Mn[Fe(CN)6] as well as KGd[Fe(CN)6][65] and KEu[Fe(CN)6] [22] have a ls-Fe(II) which occupies the C-bound position in the [Fe(CN)6]4− ion while the complexed Fe in K57Fe[Co(CN)6] has a hs-Fe(II) which takes the N-bound position to the [Co(CN)6]3− ion.

2. Experiments and Materials

2.1. L-edge XAS measurements

Iron (Fe), manganese (Mn) and cobalt (Co) L-edge XAS spectra (or L XAS) for K2Mn[Fe(CN)6] as well as for its comparison samples, reference samples or energy calibration samples were measured at the undulator beamline 4.0.2 at the Advanced Light Source (ALS) in Berkeley, California. As previous reported [29–31, 36, 38], powdered solid state samples were grounded and pressed onto an ultra-high vacuum (UHV) compatible double stick carbon tape on the sample holder at room temperature, and loaded into a UHV compatible measurement chamber as illustrated in Figure 2(a).

Figure 2.

Figure 2.

Open in a new tab

(a) A schematic drawing for 3d metal L-edge X-ray absorption spectroscopy (L XAS) measurement apparatus under ultrahigh vacuum (UHV); (b) a TEM image of the main sample - polyvinylpyrrolidone (PVP) coated K2Mn[Fe(CN)6] nanoparticles (PVP-coated Mn-PB NPs for short). The yellow circles are used as an eye-guide; (c) IR spectra for PVP (green), bulk Mn-PB (red) and PVP-coated Mn-PB NPs (blue).

Although all the samples in this publication are not air sensitive, to better control the surface condition (due to the fact that L-edge XAS is extremely surface sensitive [36, 38], the samples were ground, spread and mounted inside a nitrogen atmosphere glovebox maintained at an oxygen level of 1 ppm or less and then loaded into the UHV chamber via a vacuum compatible loadlock [Figure 2(a), upper right corner]. While the X-ray beam scanned through the intended energy region(s), Fe or Mn or Co L-edge XAS spectra were recorded using a channeltron electron multiplier [29–31, 36, 38] [Figure 2(a), lower right corner] to detect the emitted total photoelectrons whose intensity is proportional to the amount of X-ray absorption in the corresponding samples. Such spectra were further normalized to the incident radiation intensity monitored by using the photocurrent from a gold mesh [[Figure 2(a), left side]. Energy calibration was performed with appropriate standards before and after each set of the measurements. We noticed that there is no absolute energy calibration standard in the previous reports, the following standards and energy positions are chosen in this publication: Fe L-edge calibrations used the lowest energy L3 peak of Fe2O3 at 707.8 eV, Mn L-edge calibrations used the peak with the highest intensity of MnF2 at 640.0 eV, while Co L-edge was calibrated to the first sharp peak of Co(II)O at 778.8 eV. To reduce the possible radiation damage, the monochromator’s slits are set to 5 μm to decrease the beam flux to the order of 1011 photons/s and such obtained X-ray beam was further de-focused to 1×1 mm2 in its cross-section size on the sample. The energy resolution is at 0.1 – 0.2 eV.

2.2. NRVS measurements

NRVS spectra were recorded using a published procedure [28, 48, 49, 55] at SPring-8 beamlines BL09XU [66] in Japan. A high heat load monochromator (HHLM) produced 14.4 keV radiation with ~1.0 eV energy resolution, and a high energy resolution monochromator (HRM) [with crystals of Ge(422) and Si(975)x2] [66–68] subsequently produced 14.4 keV radiation with 0.8 meV energy resolution, suitable for measuring vibrations. The beam flux was ~1.8×109 photons/s at the time of the measurements. During NRVS measurements, the samples were maintained at a cryogenic temperature (e.g. 10K at the temperature sensor) using a liquid helium cryostat. However, the real sample temperatures [28] derived from anti-Stoke/Stoke intensity ratios from the NRVS spectra were found to be 40–60K instead. As illustrated in Figure 1(d), while an incident X-ray beam (the thick blue) scans through an interested energy region to cover the nuclear transition (e.g., 14.4 keV for 57Fe) and the associated vibrations (e.g. Fe-CN), the extremely narrow bandwidth for the nuclear back radiation hν1 (the thin black line) can be used as an excellent intrinsic “spectrometer” to “measure” the scattered energy in precision while the signal vs. background can be distinguished in the time domain, just like LIF does [57–59]. NRVS thus does not need a low-throughput (diffraction based) spectrometer for filtering the scattered beam and thus have a much higher photon in and photon out efficiency in comparison with IXS which also measures vibrations [28]. The total intensities collected from both the direct nuclear fluorescence at hν1 (the thin black line) and the internally converted electron K shell fluorescence at hν2 (the thick and short black line) were recorded with a 2×2 avalanche photodiode (APD) array [28, 55]. This signal vs. the vibrational energy (Evib) forms a raw NRVS spectrum. NRVS has many prominent advantages, including being able to be converted to a partial vibrational density of state (PVDOS). The raw NRVS → PVDOS conversion is obtained with PHOENIX software package or a web-based version of PHOENIX [28, 56]. The detailed information about the NRVS instruments, measurement and analysis are the same as those published widely [28, 45–49, 55, 56] and will not be repeated here.

2.3. Sample preparation and basic characterization

The main sample, polyvinylpyrrolidone (briefed as PVP, chemical formula = C10H15NO3) coated K2Mn[Fe(CN)6] nanoparticles (Mn-PB NPs for short), was prepared with a procedure as published earlier [19, 20] and described in brief in SI.2. The proposed structure for Mn-PB is similar with the PB shown in Figure S1 except its hs-Fe(III) sites are substituted with Mn and an Mn:Fe = 1:1 ratio is maintained while K+ was used to balance the extra negative charge. PB was used as a platform and PVP was used as a coating agent to prevent the Mn-PB nanoparticles from agglomerating and to improve its chemical stability and biological compatibility. The as-synthesized nanoparticles were dialyzed in a semi-permeable membrane in distilled water. Any unbound PVP should effectively be removed during this process. From a transmission electron microscopy (TEM) image as shown in Figure 2(b), the PVP-coated Mn-PB NPs are 5 – 20 nm in size and are well separated from one another. No chunks of PVP or mixture of PVP and PB were observed. Characterization and in vitro as well as in vivo MRI studies of the Mn- PB NPs are similar as the one reported previously [69].

The IR spectra of PVP coated Mn-PB NPs (blue), bulk Mn-PB (red) and PVP (green) were measured and are shown as in Figure 2(c). The IR spectra of the PVP coated Mn-PB NPs and the uncoated Mn-PB both show characteristic C≡N stretching vibrations at ~2073 cm−1 and 2082 cm−1 [not appearing as separate peaks in Figure 2(c) due to the wide plotting range to show all the features]. The IR spectrum for Mn-PB NPs shows additional bands at 1650 cm−1, 1421 cm−1 and 1280 cm−1, which overlap with the bands for PVP. This and the TEM photo in Figure 2(b) show that PVP is covering the Mn-PB NPs’ surface. The presence of water is also confirmed by the peak at 3465 cm−1 (O-H stretching) and is consistent with the fact that PVP is hydrophilic. The thickness for the PVP-coating is estimated less than 10 nm, which can let at least 98% of the soft X-ray (> 630 eV) pass through its layer and reach the Mn-PB NPs samples. For NRVS, the transmission of X-ray at 14.4 keV of the 10 nm PVP is close to 100%.

The structural analogs, KGd[Fe(CN)6] and KEu[Fe(CN)6], were synthecized with the same procedure described in SI.2 [19, 20] but by introducing Eu, Gd sources (instead of Mn source) to the K4[Fe(CN)6] complex. The 57Fe enriched K57Fe[Co(CN) 6] was produced with a similar procedure by introducing 57Fe source (e.g. 57FeCl2) to the K3[Co(CN)6] complex alternatively. The NRVS spectrum for (NH4)2Mg[57Fe(CN)6] was directed cited from the previous publications [22, 28]. The comparison samples in this study, MnF2, K3[Co(CN)6], FeO, K4[Fe(CN)6], and K3[Fe(CN)6], were purchased from commercial sources and used without further process. Additional energy calibration samples, Fe2O3, and CoO, were also purchased from commercial sources and used without further process.

For better control of their surface condition, all the samples, include the main sample and all the comparison, reference and energy calibration samples were stored inside an N2 based glovebox for over 7 days before loading into the measurement chamber for L XAS measurement. For NRVS measurement, this step becomes unnecessary.

3. Results and Discussions

In general, oxidation state is one of the most-pursued chemical properties. Resolved oxidation states or electron/charge densities have helped the understanding of many chemical processes [36, 70], while an unresolved oxidation state has contributed to many longstanding controversies in history [71–76]. This is especially true for transitional metal complexes [36, 70]. L-edge XAS for 3d metals which measures the 2p → 3d transition is one of the best methods to investigate the oxidation states and electronic spin state via L3 absorption edge positions or their centroid energies. For example, L XAS exhibits about 2 eV change in their L3 centroids per oxidation state change (eV/oxi) for the Mn complexes and 0.9 eV/oxi for Ni complexes [29, 36, 77]. The ls-Ni(II) also has a higher L3 centroid than the hs-Ni(II). For Mn complexes, the branching ratio of L3/(L3+L2) sometimes also has been used to determine the Mn oxidation states, where the L3 and L2 mean the integrated intensities at the L3 and L2 edges respectively [36, 77]. These L-edge centroids are often sufficient to assign the oxidation states.

The spectral multiplets are more essential to identify metal’s oxidation states, electronic spin states and its coordination symmetries [36, 38, 77–80]. The match of their spectral multiplets in two spectra indicates that the two samples have the same metal sites (or at least extremely similar metal sites). Due to its fingerprint-like multiplets, L-edge XAS is sensitive to and has been widely used to identify the oxidation states, spin states and other information mentioned above for metal centres in various 3d transition metal complexes and metalloenzymes [36, 38]. For example, it has been used to identify Ni(I, II, III) and even Ni(II) with different electronic spin state (hs vs. ls) successfully [37–39].

3.1. Manganese L-edge XAS

The Mn L-edge XAS for our nanoparticulated K2Mn[Fe(CN)6] is shown as in Figure 3(a). It shows an almost identical multiplet feature in both L3 and L2 regions as the one for MnF2 [Figure 3(b)]. The latter is well known to have a hs-Mn(II) center [81], making our assignment of the Mn center in K2Mn[Fe(CN)6] as a hs-Mn(II) rather reliable. In comparison with the Mn L-edge XAS for various other complexes with various Mn oxidation states and spin states in Figure S2 and Figure S3 in SI.3, our Mn L-edge XAS for K2Mn[Fe(CN)6] [Figure 3(a)] is similar to that of the MnO (Figure S2, the bottom curve in the left panel) [78, 82] and MnF2 (Figure S2, the second curve from the top in the right panel) [36, 81] which have a hs-Mn(II). On the other hand, it is very different from those of the other Mn complexes with oxidation states ranging from +3 to +7 (Figure S2, left panel) [36, 78] or from more covalent Mn(II) complexes (Figure S2, right panel) [81]. In comparison with Figure 3(a) (oxidation state = +2), most of the L-edge XAS in the left panel of Figure S2 (oxidation state = +3 to +7) have higher L3 peak centroids, reflecting the correlation between the oxidation state and the L3 centroid. These observations are consistent with the discussion in the associated reference [36, 78, 79, 81].

Figure 3.

Figure 3.

Open in a new tab

Mn L-edge XAS for K2Mn[Fe(CN)6] (a) and MnF2 (b).

According to a previous publication [81] and as re-illustrated in Figure S3, the ls-Mn(II) in [Mn(CN)6]4− ion[81] shows a sharp peak at 638.6 eV which is well separated from the rest of the L3 multiplets. This is a quite unique feature for a [Mn(CN)6]4− [81]. The fact that K2Mn[Fe(CN)6] does not have this feature (especially the lack of a “pre-L3” peak at 638.6 eV) indicates the Mn(II) in K2Mn[Fe(CN)6] is not in the C-bound position as that in the [Mn(CN)6]4− ion. Although there is no particular L XAS report found for [Mn(CN)6]3−, previous reports revealed that there are about 2 eV L3 centroid shift between Mn(II) and Mn(III) [36, 83], excluding the possibility of a [Mn(CN)6]3− site as well. Taken as a whole, our L XAS data show that the complexed Mn is not in the C-bound position in 6CN−, or in other words, it could occupy the position of the N-bound hs-Fe(III) site in PB (Figure S1). This in turn implies that Fe in K2Mn[Fe(CN)6] should remain in the C-bound position in the [Fe(CN)6]4− ion

3.2. Cobalt L-edge XAS

K2Mn[Fe(CN)6] was prepared by introducing a Mn(II) source (i.e,. MnCl2) into K4Fe(CN)6 to form a PB analog compound (SI.2) [19, 20]. According to L XAS [Figure 3(a) vs. Figure 3(b), Figure S2, and Figure S3], Mn is found to be in the N-bound position in PB (Figure S1). In an “opposite” approach, an 57Fe(II) source (i.e,. 57FeCl2) was complexed into the [Co(CN)6]3− ion to form an alternative PB analog compound of K57Fe[Co(CN)6] where Co should remain in the C-bound position in the [Co(CN)6]3− ion. Therefore, Co vs. Mn L XAS can provide a meaningful comparison insight into the two different cases. For this purpose, Figure 4 shows the Co L XAS for the comparison samples K57Fe[Co(CN)6][Figure 4(a)] and the reference sample K3[Co(CN)6][Figure 4(b)].

Figure 4.

Figure 4.

Open in a new tab

Co L-edge XAS for K57Fe(II)Co(III)(CN)6 (a) and K3Co(III)(CN)6 (b).

First, Figure 4(b) satisfactorily reproduced the previously reported results on the same complex (Figure S4 left panel, the bottom curve) [84, 85], establishing a good reference spectrum for the ls-Co(III) in [Co(CN)6]3−. The fact that Co L XAS spectrum for KFe[Co(CN)6][Figure 4(a)] has an overall resemblance as well as the same characteristic feature for the ls-Co(III) in K3[Co(CN)6] [Figure 4(b)] shows that the Co in KFe[Co(CN)6] is in the C-bound position in [Co(CN)6]3− [84]. There are some minor differences in the intensity ratio and peak width, but the overall feature resembles each other pretty well. We noticed that our spectrum for K3[Co(CN)6] [Figure 4(b)] also has a slight difference in peak positions in comparison with the previous reports (Figure S4, left panel, the bottom curve) [84], probably due to the minor difference in energy calibrations.

On the other hand, when comparing with L XAS reports for other Co complexes in Figure S4 [84–89], our Co L XAS for KFe[Co(CN)6] appears to be very different from them. In particular, the Co L XAS for KFe[Co(CN)6] has a very different multiplet from the L XAS for the Co in the N-bound position in other PB analogs, such as in ACo[Fe(CN)6].xH2O (A = Na or K) (the left panel of Figure S4, top two curves). This rules out the possibility that the Co in KFe[Co(CN)6] is in the N-bound position to the [Fe(CN)6]4− ion. In addition, its spectroscopic feature is also very different from the Co L XAS features of various Co(II), ls-Co(III) and hs-Co(III) complexes (Figure S4 left and right panels) [84–89]. In short, the L XAS for KFe[Co(CN)6] in Figure 4(a) only resembles the L-edge XAS of a ls-Co(III) in a [Co(CN)6]3− ion [e.g. Figure 4(b) or the reported spectrum in Figure S4 (the bottom curve at the left panel)]. The Co(III) in a strong ligand field created from the 6CN− ions has to be a ls-Co(III) instead of a hs-Co(III). This observation is not unexpected, just like the Fe is a ls-Fe(II) in K2Mn[Fe(CN)6].

3.3. Iron L-edge XAS

Sections 3.1 and 3.2 present a comparison of L XAS features between Mn and Co – the former is in the N-bound position while the latter is in the C-bound position. This in turn puts their Fe in different positions in the PB structure and the two complexes should have different Fe L XAS spectra.

In this section, the Fe L XAS of K2Mn[Fe(CN)6] [Figure 5(a), solid line] and its comparison complex KFe[Co(CN)6] [Figure 5(b), solid line] are evaluated. K2Mn[Fe(CN)6] shows a typical spectral feature of a ls-Fe(II) especially when it is compared with that of the ls-Fe(II) in K4Fe(CN)6 [Figure 5(a), dashed line, or Figure S5, the left panel (a) – dark line][90]. This spectral feature is also similar to those of several other ls-Fe(II) complexes cited in Figure S5 [the right panel (c)–(e)] [91]. There is no surprise because these cited complexes all have CO or CO/CN ligands, while both CO and CN are very similar strong ligands [92–94]. On the other hand, the Fe L XAS of K2Mn[Fe(CN)6] [Figure 5(a), solid line] does not have any similarity with the Fe(0) in (NEt4)2Fe0(CO)3(CN)2 or / Fe(I) in FeI(pdt)(PMe3)(CN)(CO)4 in Figure S5 [the right panel (a)–(b)] [91] or Fe(III) in other references not cited in Figure S5, including FeO(OH)2 [95], Fe2O3 [96] FeF3 [96], FeNO3 [97]. In particular, the Fe L XAS for the ls-Fe(III) in K3[Fe(CN)6] [Figure 5(c)] has a prominent sharp peak at ~706 eV, while Fe(II) in K4[Fe(CN)6] or K2Mn[Fe(CN)6] [Figure 5(a)] does not have this feature. This stand-alone peak is the major characteristic feature of the d5 ls-Fe(III) [90, 98] – the only difference among different d5 ls-Fe(III) complexes is how far this peak is from the highest L3 peak. In addition to the re-measurement [Figure 5(c)], a published L XAS spectrum for K3[Fe(CN)6] is also cited from reference [90] and re-presented in Figure S5 [the left panel (b) – dark line]. From the comprehensive comparison, K2Mn[Fe(CN)6] certainly has a ls-Fe(II) feature rather than a ls-Fe(III) feature [98].

Figure 5.

Figure 5.

Open in a new tab

Fe L-edge XAS for K2Mn[Fe(CN)6] (a, solid line), K4[Fe(CN)6] (a, dashed line), KFe[Co(CN)6] (b, solid line), FeO (b, dashed line) and K3Fe(III)(CN)6 which has a sharp characteristic peak at 706 eV (c). The complexes in (a) have a ls-Fe(II), the ones in (b) have a hs-Fe(II), the one in (c) has a ls-Fe(III).

Figure 5(b) shows a hs-Fe(II) in the N-bound position connecting to the [Fe(CN)6]4− ion, in contrast to the ls-Fe(II) in [Fe(CN)6]4− shown in Figure 5(a) or Figure S5 - the left panel (a). We, therefore, assign the comparison complex KFe[Co(CN)6] to have a hs-Fe(II) in the N-bound position.

Comparison between the Mn/Fe L-edge XAS for K2Mn[Fe(CN)6] vs. Fe/Co L-edge XAS for KFe[Co(CN)6] provides the readers with a clear understanding and an overall picture about the electronic properties for the Mn, Fe, and Co. Specifically, the ls-Fe(II) in C-bound position [Figure 5(a)] is consistent with the hs-Mn(II) in the N-bound position [Figure 3(a)] for K2Mn(II)[Fe(II)(CN)6] and the hs-Fe(II) in the N-bound position [Figure 5(b)] is consistent with the ls-Co(III) in the C-bound position [Figure 4(a)] for KFe(II)[Co(CN)6].

Photoreduction in SR beam is often an issue for L-edge XAS measurements because the beam intensity is high, while the soft X-ray penetration depth is very small [99]. For example, Colison et al. [98] found that K3[Fe(CN)6] or [Co (acac)3] can be photo reduced from Fe(III) to Fe(II) species in 26 mins or from Co(III) to Co(II) species in 20 mins. To ensure that the Mn(II), Co(III) and Fe(II) in our samples were not produced from the photoreduction (or oxidation), we used a heavily defocused beam of 1×1 mm2 in the beam size to greatly reduce the beam brightness and thus the photo-reduction rate (by 2–3 orders) in order to prevent or at least minimize such problem. In addition, a reduced beam flux was also obtained by setting much narrower beam slits as described in detail in the experimental section. To further evaluate the issue, we also quickly scanned on fresh points and frequently change the measurement spots using a beam size of 0.5×0.5 mm2 and 3 time increased beam flux (and thus 12 time increased beam brightness). No photoreduction has been found for the complexes subjected to this testing condition, let alone under the real measurement condition. For example, we did not see any Fe(III), Mn(III) or Co(II) even in the first 1 minute of each rapid scan on fresh points under the increased beam brightness. We did perform a few series of repeated testing scans in several spots and did not find any change in the spectral features during the whole time periods of over 3–5 hours each. Nevertheless, all the L-edge XAS spectra presented in this study are only from the individual scans in fresh points.

In short, the comprehensive L XAS analysis on Mn, Co, Fe inside K2Mn[Fe(CN)6] as well as its comparison complex KFe[Co(CN)6] provides the site specific information on the oxidation states and spin states for these metals, which is critical in evaluating the new, non-gadolinium MRI contrast agents. In particular, our L XAS indicates that K2Mn[Fe(CN)6] contains a hs-Mn(II) and an ls-Fe(II), leading to a total spin per molecule of 5/2. This is suitable for an MRI agent.

3.4. 57Fe NRVS

Since L-edge XAS and IR measurements are surface sensitive methods, bulky sensitive 57Fe-specific NRVS is an excellent addition to evaluate the Fe information in various PB-like complexes. Similar to other vibrational spectroscopies, NRVS is sensitive to the oxidation states and has been widely used to assign the oxidation states for 57Fe sites in different complexes and enzymes [28, 48, 49, 54]. It also provides the ligand identity and symmetry around the 57Fe site(s) [63, 64]. For PB or PB-like compounds, NRVS can also indicate whether the spectral feature is from the Fe in the C-bound position in [Fe(CN)6]4− or from the off-sphere N bound position [22, 28].

The PB NRVS has two major peaks [Figure 6(a), green] [22, 28]: 1) the strong interactions between the ls-Fe(II) and 6 CN− ions, which leads to a sharp peak at 594 cm−1; and 2) the weaker interaction between the off-sphere hs-Fe(III) and the [Fe(CN)6]4− ion (via Fe…N interactions), which produces an additional broad hump at 120 – 280 cm−1. Please note that the sharp peak position was mentioned in several previous publications [28, 44] at 602 cm−1, but it appears at 594 cm−1 [22] with the calibration method used in our research team (380 cm−1 for the Fe-Cl stretch peak in (Et4N)[FeCl4] [28, 55]). Although we realize that there are different energy calibration standards employed by different research teams with no effort made thus far to unify the calibration standards among different teams, using one standard in one research team is meaningful.

Figure 6.

Figure 6.

Open in a new tab

(a) NRVS spectra for 57Fe enriched PB (green), (NH4)2Mg(II)- [57Fe(II)(CN)6] [44] (blue) and K57Fe(II)[Co(III)(CN)6]; (b1-b3) skip scan measured regional NRVS peak for K2Mn(II)[Fe(II)(CN)6] (b1), KEu(III)[Fe(II)(CN)6] (b2) and KGd(III)[Fe(II)(CN)6] (b3).

To further illustrate the origin of each peak (or hump), either the C-bound ls-Fe(II) or the N-bound hs-Fe(III) in PB can be “substituted” with another metal, leaving only one site labelled with 57Fe. This approach creates two site–specific complexes: one is our comparison sample K57Fe[Co(CN)6]. Its NRVS has no peak at or around 594 cm−1 at all but has a lower energy hump at 120 – 280 cm−1 [the red curve in Figure 6(a)]. Another complex is (NH4)2Mg(II)[Fe(II)(CN)6] [44] with a [57Fe(CN)6]4− ion that is weakly bound to Mg. This complex has one strong NRVS peak at 594 cm−1 (the blue curve) but almost no hump at 120 – 280 cm−1. These NRVS spectra well-illustrate how NRVS feature(s) can be used to confidently answer the question about the locations of their Fe sites in the corresponding PB analog compounds, i.e., in the C-bound position or the N-bound position.

Since K2Mn[Fe(CN)6] is not 57Fe labelled, its NRVS thus has a very weak signal (2% 57Fe in natural abundance sample vs. 100% 57Fe in the enriched samples). Therefore, measuring a full NRVS scan is out of the question. We instead only scanned a narrow region around the nuclear resonant peak at Evib=0 (±40 cm−1) and that around the sharp peak at ~ 594 cm−1 (e.g. 380–700 cm−1 – the presentation range here is a bit less) [22, 28]. Although the exact peak position for this sharp peak cannot be precisely located due to the skip scan operation (jumping from the nuclear resonant peak region to the targeted sharp peak region) [22, 28], the obtained peak feature is sharp and clear. The energy positions are less than ±1 meV from the peak position at 594 cm−1 [Figure 6(b1-b3) vs. 6(a)], while the skip scan uncertainty can be as large as 1.5 meV. This indicates the presence of a C-bound ls-Fe(II) in [Fe(CN)6]4−, confirming the assignment based on the L-edge XAS measurements. This shows that a C-bound ls-Fe(II) is true for the sample’s bulk of K2Mn[Fe(CN)6], not just on its surface (L XAS).

Previously measured partial NRVS spectra for two unenriched samples KEu[Fe(CN)6] and KGd[Fe(CN)6] are also added to Figure 6 (b2 and b3) for comparison – both of them also have a clear feature for a characteristic peak for the C-bound ls-Fe(II) in [Fe(CN)6]4− (around 594 cm−1). On the other hand, the lack of sharp NRVS peak at or around ~ 594 cm−1 shows that the comparison complex K57Fe[Co(CN)6] does not have a C-bound ls-Fe(II). The NRVS comparison further indicates that the complexed element stays in the N-bound position, which is consistent with the Mn, Co and Fe L XAS results. For reference, in a previous publication [22], 151Eu and 57Fe NRVS were used to measure KEu[Fe(CN)6] vs. Eu[Fe(CN)6] and to conclude the complexed metal (Eu) remains in the N-bound position in PB analogs.

In addition, NRVS can also identify whether the Fe is an Fe(II) or an Fe(III) [22]. In particular, as shown in Figure S6 in SI.6 [22], the Fe(III)-(CN)6 interaction has a much lower energy position (at 516 cm−1) and a much wider peak (32 cm−1 in FWHM) than the Fe(II)-(CN)6 does (at 594 cm−1 with a 14 cm−1 FWHM). In general, this trend is not surprise for complexes with CN or CO ligands [90, 93, 94, 100, 101]. In comparison, K2Mn[Fe(CN)6]) indeed has a ls-Fe(II), not a ls-Fe(III).

4. Conclusions

In this publication, we have conducted detailed measurements of L-edge XAS on Mn and Fe, respectively, for the nanoparticulate PB analog K2Mn[Fe(CN)6] that has been synthesized and evaluated as a potential MRI agent [19, 24]. The results obtained from such L XAS experiments allow us to unambiguously conclude that K2Mn[Fe(CN)6] has a hs-Mn(II) bound to N and a ls-Fe(II) bound to C in the PB structure. For comparison, Co and Fe L XAS on KFeCo[(CN)6] show that it has a hs-Fe(II) surrounded by N and a ls-Co(III) surrounded by C in the PB structure. Accordingly, K+ ions have to be incorporated into the structure to maintain electroneutrality of the overcall formula and a ratio of Mn: Fe=1:1 or Fe:Co=1:1 for the corresponding complexes.

To rule out the possible issues of the surface effect, the bulk-sensitive 57Fe NRVS study is also performed for K2Mn[Fe(CN)6] and its reference samples KEu[Fe(CN)6] and KGd[Fe(CN)6]. The NRVS results are consistent with the above conclusions obtained from the surface sensitive L XAS.

In addition to the evaluation of its relaxvity properties of K2Mn[Fe(CN)6] to assess its suitability as a prime candidate for the next-generation non-gadolinium MRI agent, the current studies well illustrate the many significant advantages of using L XAS and NRVS in combination on the same sample in revealing the site-specific information for nanoparticulate PB analog complexes or other complexes in general.

5. Future work

In the future, it will be interesting to observe whether the so-called coordination isomers of this or similar complex(es) or certain types of solid-solutions where Mn(II) and Fe(II) ions (or other pairs of metals) are partitioned between the C-bound and the N-bound positions in PB analogs can be prepared if one uses a one-pot self-assembly synthesis involving the stoichiometric amounts of Fe(II), Mn(II), and CN−.

Supplementary Material

Supporting-Information

Acknowledgments:

L-edge XAS measurements were done at ALS BL4.0.2. ALS was supported by the Director, Office of Science, Office of Basic Energy Sciences, U.S. Department of Energy under Contract No. DE-AC03– 76SF00098. NRVS was measured at SPring-8 BL09XU (via JASRI proposal 2018A1409, 2018B1379, and 2019A1259). We also thank Dr. Murthi S. Kandanapitiye in Kent State U for his assistance in synthesizing PB analog samples in this study.

Funding:

This work was supported by NIH grant R01-GM-65440 (to S.P.C., for NRVS and L XAS).

Footnotes

Supplementary Materials: The supporting information (SI) can be downloaded at: www.mdpi.com/xxx/s1.

Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

References

  • 1.Geraldes CFGC and Laurent S, Classification and basic properties of contrast agents for magnetic resonance imaging. Contrast Media & Molecular Imaging, 2009. 4(1): p. 1–23. [DOI] [PubMed] [Google Scholar]
  • 2.Tınaz Ş and Stern CE, Principles of Functional Magnetic Resonance Imaging and its Applications in Cognitive Neuroscience. Turk J Neurol, 2005. 11(1): p. 8–26. [Google Scholar]
  • 3.Parizel PM, et al. , Magnetic Resonance Imaging of the Brain, in Clinical MR Imaging, Reimer P, et al., Editors. 2010, Springer Berlin Heidelberg: Berlin, Heidelberg. p. 107–195. [Google Scholar]
  • 4.Llamas M Gadolinium-Based Contrast Agents. 2022; Available from: https://www.drugwatch.com/gadolinium/.
  • 5.Fraum TJ, et al. , Gadolinium-based contrast agents: A comprehensive risk assessment. J Magn Reson Imaging, 2017. 46(2): p. 338–353. [DOI] [PubMed] [Google Scholar]
  • 6.Wahsner J, et al. , Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers. Chemical Reviews, 2019. 119(2): p. 957–1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Cowper SE, et al. , Lancet, 2000. 356: p. 1000. [DOI] [PubMed] [Google Scholar]
  • 8.George SJ, et al. , Synchrotron X-ray analyses demonstrate phosphate-bound gadolinium in skin in nephrogenic systemic fibrosis. British Journal of Dermatology, 2010. 163(5): p. 1077–1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Perazella MA, Current Status of Gadolinium Toxicity in Patients with Kidney Disease. Clinical Journal of the American Society of Nephrology, 2009. 4(2): p. 461–469. [DOI] [PubMed] [Google Scholar]
  • 10.Weller A, Barber JL, and Olsen ØE, Gadolinium and nephrogenic systemic fibrosis: an update. Pediatric Nephrology, 2014. 29(10): p. 1927–1937. [DOI] [PubMed] [Google Scholar]
  • 11.Le Fur M and Caravan P, The biological fate of gadolinium-based MRI contrast agents: a call to action for bioinorganic chemists. Metallomics, 2019. 11(2): p. 240–254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Schieda N, et al. , Gadolinium-Based Contrast Agents in Kidney Disease: A Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists. Canadian Journal of Kidney Health and Disease, 2018. 5: p. 2054358118778573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Do C, et al. , Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution. Kidney360, 2020. 1(6): p. 561–568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.FDA. FDA Drug Safety Communication: FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings. 2017; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body.
  • 15.Winter MB, et al. , Porphyrin-Substituted H-NOX Proteins as High-Relaxivity MRI Contrast Agents. Inorganic Chemistry, 2013. 52(5): p. 2277–2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Young IR, et al. , Enhancement of Relaxation Rate with Paramagnetic Contrast Agents in Nmr Imaging. Ct-Journal of Computed Tomography, 1981. 5(6): p. 543–547. [DOI] [PubMed] [Google Scholar]
  • 17.Tan M, et al. , Synthesis and Evaluation of Nanoglobular Macrocyclic Mn(II) Chelate Conjugates as Non-Gadolinium(III) MRI Contrast Agents. Bioconjugate Chemistry, 2011. 22(5): p. 931–937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Gallez B, et al. , Accumulation of manganese in the brain of mice after intravenous injection of manganese-based contrast agents. Chemical Research in Toxicology, 1997. 10(4): p. 360–363. [DOI] [PubMed] [Google Scholar]
  • 19.Shokouhimehr M, et al. , Dual purpose Prussian blue nanoparticles for cellular imaging and drug delivery: a new generation of T-1-weighted MRI contrast and small molecule delivery agents. Journal of Materials Chemistry, 2010. 20(25): p. 5251–5259. [Google Scholar]
  • 20.Kandanapitiye MS, et al. , Gallium Analogue of Soluble Prussian Blue KGa Fe(CN)(6) center dot nH(2)O: Synthesis, Characterization, and Potential Biomedical Applications. Inorganic Chemistry, 2013. 52(6): p. 2790–2792. [DOI] [PubMed] [Google Scholar]
  • 21.Organization, W.H. World Health Organization model list of essential medicines: 21st list. 2019; Available from: https://apps.who.int/iris/handle/10665/325771.
  • 22.Wang H, et al. , Europium-151 and iron-57 nuclear resonant vibrational spectroscopy of naturally abundant KEu(iii)Fe(ii)(CN)6 and Eu(iii)Fe(iii)(CN)6 complexes. Dalton Transactions, 2022. 51(46): p. 17753–17761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Buser HJ, et al. , The crystal structure of Prussian Blue: Fe4[Fe(CN)6]3.xH2O. Inorganic Chemistry, 1977. 16(11): p. 2704–2710. [Google Scholar]
  • 24.Huang SD, et al. , Nanoparticulate manganese MRI contrast agents, in Google: https://patents.google.com/patent/WO2012108856A1/en. 2011, Kent State University: USA. p. 1–24. [Google Scholar]
  • 25.Shin J, et al. , Hollow Manganese Oxide Nanoparticles as Multifunctional Agents for Magnetic Resonance Imaging and Drug Delivery. Angewandte Chemie International Edition, 2009. 48(2): p. 321–324. [DOI] [PubMed] [Google Scholar]
  • 26.DeBeer George S, et al. , A Quantitative Description of the Ground-State Wave Function of CuA by X-ray Absorption Spectroscopy:  Comparison to Plastocyanin and Relevance to Electron Transfer. Journal of the American Chemical Society, 2001. 123(24): p. 5757–5767. [DOI] [PubMed] [Google Scholar]
  • 27.Gu WW, et al. , Refinement of the nickel site structure in Desulfovibrio gigas hydrogenase using range-extended EXAFS spectroscopy. Journal of Inorganic Biochemistry, 2003. 93(1–2): p. 41–51. [DOI] [PubMed] [Google Scholar]
  • 28.Wang H, et al. , Nuclear Resonance Vibrational Spectroscopy: A Modern Tool to Pinpoint Site-Specific Cooperative Processes. Crystals, 2021. 11(8): p. 909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Cressey G, Henderson CMB, and van der Laan G, Use of L-edge X-ray absorption spectroscopy to characterize multiple valence states of 3d transition metals; a new probe for mineralogical and geochemical research. Physics and Chemistry of Minerals, 1993. 20(2): p. 111–119. [Google Scholar]
  • 30.Baker ML, et al. , K- and L-edge X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS) determination of differential orbital covalency (DOC) of transition metal sites. Coordination Chemistry Reviews, 2017. 345: p. 182–208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Xi L, et al. , In Situ L-Edge XAS Study of a Manganese Oxide Water Oxidation Catalyst. The Journal of Physical Chemistry C, 2017. 121(22): p. 12003–12009. [Google Scholar]
  • 32.Penner-Hahn JE, et al. , Structural Characterization of the Manganese Sites in the Photosynthetic Oxygen-Evolving Complex Using X-Ray Absorption Spectroscopy. Journal of the American Chemical Society, 1990. 112(7): p. 2549–2557. [Google Scholar]
  • 33.Westre TE, et al. , A multiplet analysis of Fe K-edge 1s->3d pre-edge features of iron complexes. Journal of the American Chemical Society, 1997. 119(27): p. 6297–6314. [Google Scholar]
  • 34.Penner-Hahn JE, X-ray Absorption Spectroscopy, in eLS. 2005, Wiley Online Library. [Google Scholar]
  • 35.Stöhr J, NEXAFS Spectroscopy. 2003, New York: Springer-Verlag. [Google Scholar]
  • 36.Wang H, et al. , L-edge sum rule analysis on 3d transition metal sites: from d10 to d0 and towards application to extremely dilute metallo-enzymes. Physical Chemistry Chemical Physics, 2018. 20(12): p. 8166–8176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.de Groot F, High resolution X-ray emission and X-ray absorption spectroscopy. Chemical Reviews, 2001. 101(6): p. 1779–1808. [DOI] [PubMed] [Google Scholar]
  • 38.Wang HX, et al. , Nickel L-edge soft X-ray spectroscopy of nickel-iron hydrogenases and model compounds - Evidence for high-spin nickel(II) in the active enzyme. Journal of the American Chemical Society, 2000. 122(43): p. 10544–10552. [Google Scholar]
  • 39.Funk T, et al. , X-ray magnetic circular dichroism - a high energy probe of magnetic properties. Coordination Chemistry Reviews, 2005. 249(1–2): p. 3–30. [Google Scholar]
  • 40.Kuiper P, et al. , Resonant X-Ray Raman Spectra of Cu $\mathit{dd}$ Excitations in ${\mathrm{Sr}}_{2}{\mathrm{CuO}}_{2}{\mathrm{Cl}}_{2}$. Physical Review Letters, 1998. 80(23): p. 5204–5207. [Google Scholar]
  • 41.Freelon B, et al. , Electron correlation and charge transfer in superconducting superlattices. Phys Rev Lett, 2006. 96(1): p. 017003. [DOI] [PubMed] [Google Scholar]
  • 42.Kapilashrami M, et al. , Probing the Optical Property and Electronic Structure of TiO2 Nanomaterials for Renewable Energy Applications. Chemical Reviews, 2014. 114(19): p. 9662–9707. [DOI] [PubMed] [Google Scholar]
  • 43.Jang J-W, et al. , Enabling unassisted solar water splitting by iron oxide and silicon. Nature Communications, 2015. 6(1): p. 7447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Chumakov AI, et al. , Insight to Dynamics of Molecules with Nuclear Inelastic Scattering. Structural Chemistry, 2003. 14(1): p. 109–119. [Google Scholar]
  • 45.Seto M, et al. , Observation of Nuclear Resonant Scattering Accompanied by Phonon Excitation Using Synchrotron Radiation. Physical Review Letters, 1995. 74(19): p. 3828–3831. [DOI] [PubMed] [Google Scholar]
  • 46.Sturhahn W, et al. , Phonon Density of States Measured by Inelastic Nuclear Resonant Scattering. Physical Review Letters, 1995. 74: p. 3832–3835. [DOI] [PubMed] [Google Scholar]
  • 47.Chumakov AI, et al. , Energy Dependence of Nuclear Recoil Measured with Incoherent Nuclear Scattering of Synchrotron Radiation. EPL (Europhysics Letters), 1995. 30(7): p. 427. [Google Scholar]
  • 48.Ogata H, et al. , Hydride bridge in [NiFe]-hydrogenase observed by nuclear resonance vibrational spectroscopy. Nat Commun, 2015. 6: p. 7890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Guo Y, et al. , Characterization of the Fe site in iron-sulfur cluster-free hydrogenase (Hmd) and of a model compound via nuclear resonance vibrational spectroscopy (NRVS). Inorganic Chemistry, 2008. 47(10): p. 3969–3977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Dong W, et al. , Infrared measurements on ultraviolet photolysis products at cryogenic temperatures. Infrared Physics & Technology, 2013. 56: p. 51–56. [Google Scholar]
  • 51.Petit S and Madejova J, Chapter 2.7 - Fourier Transform Infrared Spectroscopy, in Developments in Clay Science, Bergaya F and Lagaly G, Editors. 2013, Elsevier. p. 213–231. [Google Scholar]
  • 52.Gilbert-Wilson R, et al. , Spectroscopic Investigations of [FeFe] Hydrogenase Maturated with [57Fe2(adt)(CN)2(CO)4]2–. Journal of the American Chemical Society, 2015. 137(28): p. 8998–9005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Birrell JA, et al. , Spectroscopic and Computational Evidence that [FeFe] Hydrogenases Operate Exclusively with CO-Bridged Intermediates. Journal of the American Chemical Society, 2020. 142(1): p. 222–232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Scheidt WR, Li J, and Sage JT, What Can Be Learned from Nuclear Resonance Vibrational Spectroscopy: Vibrational Dynamics and Hemes. Chemical Reviews, 2017. 117(19): p. 12532–12563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Wang J, Li L, and Wang H, Machine learning concept in de-spiking process for nuclear resonant vibrational spectra – Automation using no external parameter. Vibrational Spectroscopy, 2022. 119: p. 103352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Sturhahn W, CONUSS and PHOENIX: evaluation of nuclear resonant scattering data. Hyperfine Interactions, 2000. 125: p. 149–172. [Google Scholar]
  • 57.Wang H, Salzberg AP, and Weiner BR, Laser ablation of aluminum at 193, 248, and 351 nm. Applied Physics Letters, 1991. 59(8): p. 935–937. [Google Scholar]
  • 58.Barnhard KI, He M, and Weiner BR, Excited-State Dynamics of CH2CHO (B̃2A’’). The Journal of Physical Chemistry, 1996. 100(8): p. 2784–2790. [Google Scholar]
  • 59.Wu F, Chen X, and Weiner BR, The Photochemistry of Ethylene Episulfoxide. Journal of the American Chemical Society, 1996. 118(35): p. 8417–8424. [Google Scholar]
  • 60.Murai N, et al. , Lattice dynamics in FeSe via inelastic x-ray scattering and first-principles calculations. Physical Review B, 2020. 101(3): p. 035126. [Google Scholar]
  • 61.Mitra D, et al. , Characterization of [4Fe-4S] Cluster Vibrations and Structure in Nitrogenase Fe Protein at Three Oxidation Levels via Combined NRVS, EXAFS, and DFT Analyses. Journal of the American Chemical Society, 2013. 135(7): p. 2530–2543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Lauterbach L, et al. , Characterization of the [3Fe–4S]0/1+ cluster from the D14C variant of Pyrococcus furiosus ferredoxin via combined NRVS and DFT analyses. Dalton Transactions, 2016. 45(17): p. 7215–7219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Reijerse EJ, et al. , Direct Observation of an Iron-Bound Terminal Hydride in [FeFe]-Hydrogenase by Nuclear Resonance Vibrational Spectroscopy. Journal of the American Chemical Society, 2017. 139(12): p. 4306–4309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Pelmenschikov V, et al. , Vibrational Perturbation of the [FeFe] Hydrogenase H-Cluster Revealed by (13)C(2)H-ADT Labeling. J Am Chem Soc, 2021. 143(22): p. 8237–8243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Wang H, et al. , Energy calibration issues in nuclear resonant vibrational spectroscopy: observing small spectral shifts and making fast calibrations. Journal of Synchrotron Radiation, 2013. 20(5): p. 683–690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Yoda Y, et al. , Upgrade of the nuclear resonant scattering beamline, BL09XU in SPring-8. Hyperfine Interactions, 2012. 206: p. 83. [Google Scholar]
  • 67.Chumakov AI, et al. , An X-ray monochromator with 1.65 meV energy resolution. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 1996. 383(2): p. 642–644. [Google Scholar]
  • 68.Toellner TS, et al. , A cryogenically stabilized meV-monochromator for hard X-rays. Journal of Synchrotron Radiation, 2006. 13(2): p. 211–215. [DOI] [PubMed] [Google Scholar]
  • 69.Kandanapitiye MS, et al. , K2Mn3[FeII(CN)6]2 NPs with High T1-Relaxivity Attributable to Water Coordination on the Mn(II) Center for Gastrointestinal Tract MR Imaging. Advanced Healthcare Materials, 2021. 10(20): p. 2100987. [DOI] [PubMed] [Google Scholar]
  • 70.George SJ, et al. , Copper L-Edge Spectral Studies - a Direct Experimental Probe of the Ground-State Covalency in the Blue Copper Site in Plastocyanin. Journal of the American Chemical Society, 1993. 115(7): p. 2968–2969. [Google Scholar]
  • 71.Lippard SJ and Berg JM, Principles of Bioinorganic Chemistry. 1994, Mill Valley, CA: University Science Books. [Google Scholar]
  • 72.Albracht SPJ, Nickel Hydrogenases - In Search Of the Active Site. Biochimica Et Biophysica Acta-Bioenergetics, 1994. 1188(3): p. 167–204. [DOI] [PubMed] [Google Scholar]
  • 73.Bertini I, Gray JHB, L. S., and Valentine JS, Bioinorganic Chemistry. 1994, Mill Valley, CA: University Science Books. [Google Scholar]
  • 74.Cammack R, Fernandez VM, and Hatchikian EC, Nickel-iron Hydrogenases, in Inorganic Microbial Sulfur Metabolism, LeGall J and Peck HD Jr., Editors. 1994, Academic Press Inc.: San Diego, CA. p. 43–67. [Google Scholar]
  • 75.Pickering IJ, et al. , Nickel K-Edge X-Ray Absorption Fine Structure of Lithium Nickel Oxides. Journal of the American Chemical Society, 1993. 115(10): p. 4137–4144. [Google Scholar]
  • 76.Coyle CL and Stiefel EI, The Coordination Chemistry of Nickel: An Introductory Survey, in The Bioinorganic Chemistry of Nickel, Lancaster JR Jr., Editor. 1988, VCH Publishers: New York. p. 1–28. [Google Scholar]
  • 77.Lee J, et al. , Reversible Mn2+/Mn4+ double redox in lithium-excess cathode materials. Nature, 2018. 556(7700): p. 185–190. [DOI] [PubMed] [Google Scholar]
  • 78.Gilbert B, et al. , Multiple Scattering Calculations of Bonding and X-ray Absorption Spectroscopy of Manganese Oxides. The Journal of Physical Chemistry A, 2003. 107(16): p. 2839–2847. [Google Scholar]
  • 79.Kubobuchi K, et al. , Mn L2,3-edge X-ray absorption spectroscopic studies on charge-discharge mechanism of Li2MnO3. Applied Physics Letters, 2014. 104(5): p. 053906. [Google Scholar]
  • 80.Jeong S, et al. , Runaway Carbon Dioxide Conversion Leads to Enhanced Uptake in a Nanohybrid Form of Porous Magnesium Borohydride. Advanced Materials, 2019. 31(44): p. 1904252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Cramer SP, et al. , Ligand Field Strengths and Oxidation States from Manganese L-Edge Spectroscopy. Journal of the American Chemical Society, 1991. 113: p. 7937–7940. [Google Scholar]
  • 82.Grush MM, et al. , Manganese L-Edge X-ray Absorption Spectroscopy of Manganese Catalase from Lactobacillus plantarum and Mixed Valence Manganese Complexes. Journal of the American Chemical Society, 1996. 118(1): p. 65–69. [Google Scholar]
  • 83.Kubin M, et al. , Probing the oxidation state of transition metal complexes: a case study on how charge and spin densities determine Mn L-edge X-ray absorption energies. Chemical Science, 2018. 9(33): p. 6813–6829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Lee E, et al. , Soft x-ray absorption spectroscopy study of Prussian blue analogue ACo[Fe(CN)6]H2O nano-particles (A=Na, K). Journal of the Korean Physical Society, 2013. 62(12): p. 1910–1913. [Google Scholar]
  • 85.Lalithambika SSN, et al. , Chemical bonding in aqueous hexacyano cobaltate from photon- and electron-detection perspectives. Scientific Reports, 2017. 7(1): p. 40811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Chang CF, et al. , Spin Blockade, Orbital Occupation, and Charge Ordering in ${\mathrm{La}}_{1.5}{\mathrm{Sr}}_{0.5}{\mathrm{CoO}}_{4}$. Physical Review Letters, 2009. 102(11): p. 116401. [DOI] [PubMed] [Google Scholar]
  • 87.Istomin SY, et al. , An unusual high-spin ground state of Co3+ in octahedral coordination in brownmillerite-type cobalt oxide. Dalton Transactions, 2015. 44(23): p. 10708–10713. [DOI] [PubMed] [Google Scholar]
  • 88.Miedema PS, et al. , Oxygen Binding to Cobalt and Iron Phthalocyanines As Determined from in Situ X-ray Absorption Spectroscopy. The Journal of Physical Chemistry C, 2011. 115(51): p. 25422–25428. [Google Scholar]
  • 89.Yamagami K, et al. Soft x-ray absorption study of Co-Au multinuclear complexes with D-penicillaminates. 2016. [Google Scholar]
  • 90.Hocking RK, et al. , Fe L-Edge XAS Studies of K4[Fe(CN)6] and K3[Fe(CN)6]:  A Direct Probe of Back-Bonding. Journal of the American Chemical Society, 2006. 128(32): p. 10442–10451. [DOI] [PubMed] [Google Scholar]
  • 91.George SJ, et al. , X-ray photochemistry in iron complexes from Fe(0) to Fe(IV) – Can a bug become a feature? Inorganica Chimica Acta, 2008. 361(4): p. 1157–1165. [Google Scholar]
  • 92.Weber B, Coordination Chemistry - Basics and Current Trends. 2023: Springer. [Google Scholar]
  • 93.Pike RD, Structure and Bonding in Copper(I) Carbonyl and Cyanide Complexes. Organometallics, 2012. 31(22): p. 7647–7660. [Google Scholar]
  • 94.Frenking G, et al. , Metal–CO Bonding in Mononuclear Transition Metal Carbonyl Complexes. JACS Au, 2021. 1(5): p. 623–645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 95.Everett J, et al. , Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer’s disease peptide β-amyloid (1–42). Journal of The Royal Society Interface, 2014. 11(95): p. 20140165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96.Miedema PS and de Groot FMF, The iron L edges: Fe 2p X-ray absorption and electron energy loss spectroscopy. Journal of Electron Spectroscopy and Related Phenomena, 2013. 187: p. 32–48. [Google Scholar]
  • 97.Bhattacharyya A, et al. , Redox interactions between Fe and cysteine: Spectroscopic studies and multiplet calculations. Geochimica et Cosmochimica Acta, 2013. 122: p. 89–100. [Google Scholar]
  • 98.Collison D, et al. , Soft X-ray photochemistry at the L2,3-edges in K3[Fe(CN)6], [Co(acac)3] and [Cp2Fe][BF4]. Journal of Synchrotron Radiation, 1999. 6(3): p. 585–587. [DOI] [PubMed] [Google Scholar]
  • 99.van Schooneveld MM and DeBeer S, A close look at dose: Toward L-edge XAS spectral uniformity, dose quantification and prediction of metal ion photoreduction. Journal of Electron Spectroscopy and Related Phenomena, 2015. 198: p. 31–56. [Google Scholar]
  • 100.Parasar D, et al. , Carbonyl complexes of copper(i) stabilized by bridging fluorinated pyrazolates and halide ions. Dalton Transactions, 2019. 48(19): p. 6358–6371. [DOI] [PubMed] [Google Scholar]
  • 101.Eaton JP and Nicholls D, The complex cyanides of chromium(II) and chromium(0). Transition Metal Chemistry, 1981. 6(4): p. 203–206. [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supporting-Information
NIHMS2053388-supplement-Supporting-Information.pdf (126.8KB, pdf)

RESOURCES