Skip to main content
NCBI home page
ACS AuthorChoice logoLink to ACS AuthorChoice
. 2025 Jan 17;147(12):10231–10237. doi: 10.1021/jacs.4c15818

Strain-Induced Photochemical Opening of Ferrocene[6]cycloparaphenylene: Uncaging of Fe2+ with Green Light

Remigiusz B Kręcijasz †, Juraj Malinčík †, Simon Mathew †, Peter Štacko ‡,*, Tomáš Šolomek †,*
PMCID: PMC11951145  PMID: 39823312

Abstract

graphic file with name ja4c15818_0008.jpg

We present the synthesis, structural analysis, and remarkable reactivity of the first carbon nanohoop that fully incorporates ferrocene in the macrocyclic backbone. The high strain imposed on the ferrocene by the curved nanohoop structure enables unprecedented photochemical reactivity of this otherwise photochemically inert metallocene complex. Visible light activation triggers a ring-opening of the nanohoop structure, fully dissociating the Fe–cyclopentadienyl bonds in the presence of 1,10-phenanthroline. This process uncages Fe2+ ions captured in the form of [Fe(phen)3]2+ complex in high chemical yield and can operate efficiently in a water-rich solvent with green light excitation. The measured quantum yields of [Fe(phen)3]2+ formation show that embedding ferrocene into a strained nanohoop boosts its photoreactivity by 3 orders of magnitude compared to an unstrained ferrocene macrocycle or ferrocene itself. Our data suggest that the dissociation occurs by intercepting the photoexcited triplet state of the nanohoop by a nucleophilic solvent or external ligand. The strategy portrayed in this work proposes that new, tunable reactivity of analogous metallamacrocycles can be achieved with spatial and temporal control, which will aid and abet the development of responsive materials for metal ion delivery and supramolecular, organometallic, or polymer chemistry.

Introduction

Iron is the single most important transition metal in the human body. While primarily renowned for its role in oxygen transport and storage within hemoglobin and myoglobin,1 iron fulfills numerous other critical roles in biological systems.2 Iron is a crucial component of cytochromes involved in the energy-providing electron transport chain in mitochondria.3 Ribonucleotide reductase—an iron-dependent enzyme—is necessary in the synthesis of deoxyribonucleotides, the building blocks of DNA that are crucial for cell division and repair.4 Iron also acts as a cofactor for various enzymes responsible for protection from oxidative stress5,6 or in the synthesis/degradation of hormones and neurotransmitters.7−9 Nature has developed a sophisticated system to tightly regulate iron’s uptake and homeostasis through proteins and hormones like transferrin, ferroportin, ferritin, and hepcidin.10 This system ensures a delicate balance between meeting physiological iron needs and preventing the adverse effects of iron overload. For instance, iron levels are reduced to restrict its availability to pathogens in response to inflammation, but this action can also impair immune cell function.11−13 Artificial systems that mimic these functions or exert spatiotemporal control over iron levels are consequently attractive in the context of potential biomedical applications.

Ferrocene (Fc) with its captivating sandwich structure featuring a central iron atom represents one of the most studied organometallic compounds since its discovery in the early 1950s.14 Its popularity can be attributed to a unique combination of its redox chemistry, structural fluxionality, and exceptional chemical and photochemical stability that parallels those of aromatic compounds. In fact, the iron–cyclopentadienyl (Fe–Cp) bond dissociation energy (BDE) of ∼90 kcal mol–1 is similar to that of a typical covalent C–C bond.15 As a result, the excellent redox properties and robustness made this metallocene class of materials particularly attractive for diverse applications that span polymer science,16,17 sensing,18,19 catalysis,18,20 biochemistry,21 and molecular electronics.18,22

Imparting strain to Fc increases the propensity of this otherwise inert compound to undergo cleavage of the Fe–Cp bond. This has been successfully exploited in a light-induced ring-opening polymerization (ROP) via Fe–Cp bond dissociation in strained [n]ferrocenophanes (Estrain = 14–31 kcal mol–1).16,23−27 In these molecules, the two Cp rings are bridged via a few atoms (n = 1–2, Figure 1a) linked with single bonds. Although diverse polymers can be achieved via substitution of the bridging atoms or the Fc core itself, the linkers must be short, and they interrupt the π-conjugation in the polymer. Recently, polymers with Fc incorporated in their backbone were shown to be susceptible to mechanically triggered Fe–Cp bond scission (Figure 1a), eventually releasing Fe2+ or Fe3+ ions.28−30 Here, [n]ferrocenophanes (n = 3, 5) were also used to tune the mechanical sensitivity of the Fc mechanophore.29

Figure 1.

Figure 1

Open in a new tab

(a) Examples of photo-16,23−27 and mechanoactive28−30 [n]ferrocenophanes, and (b) conceptually new photoactive ferrocene-based π-conjugated macrocycle described in this work.

Achieving iron release on demand using benign light activation would represent a great tool to control the concentration of available iron in a sample. However, such accomplishment would require developing robust methods to tune the strain in the Fc unit to control its reactivity. Cycloparaphenylenes (CPPs)31,32 are a unique class of highly strained, curved π-conjugated macrocycles consisting solely of phenylene rings connected through para positions. CPPs and related carbon-rich molecular systems, so-called carbon nanohoops, can be modified to alter the molecular strain and curvature by manipulating the number of para-phenylene units in the macrocycle. Therefore, the CPP scaffold offers an elegant way to control the structural strain of a unit incorporated in the corresponding carbon nanohoop. We hypothesized that embedding Fc into a highly strained, fully π-conjugated macrocycle33,34 such as CPP via both Cp rings could represent a robust strategy to impose the strain on Fc, enabling the control of Fc reactivity. The resultant conjugated, shape-persistent metallocene carbon nanohoops could lead to new applications demanding light- and force-sensitive materials. Although a handful of organometallic compounds based on the CPP scaffold have been reported, the metal atom in these structures is not an integral part of the macrocyclic backbone and it is therefore subject to a lower amount of strain than what the curved CPP structures could provide.33−38

Here, we report the synthesis and properties of the first ferrocene-cycloparaphenylene Fc[n]CPP (n = 6) with Fc enclosed in a loop of six para-phenylene rings. The considerable strain imparted on the Fc unit in Fc[6]CPP enables its unprecedented photoreactivity that allows to open the nanohoop structure and release Fe2+ in high yield at ambient conditions using benign blue or green light in polar solvents (Figure 1b). The nanohoop Fc[6]CPP thus serves as a photoactivatable molecular storage system of Fe2+ ions, reminiscent of ferritin but with deliberate spatiotemporal control.

Results and Discussion

Fc[6]CPP was prepared in four steps (Scheme 1) from the reported 1,1′-diiodoferrocene and building block 1 following the methodology developed by Jasti.31 First, the Suzuki cross-coupling of 1,1′-diiodoferrocene with 1 provided intermediate 2 in a 52% yield. The chlorides in intermediate 2 were then replaced by Miyaura borylation forming diboronate 3 in 81% yield. Subsequently, the intramolecular oxidative homocoupling39 of 3 afforded the pro-aromatic macrocycle pro-Fc[6]CPP in a very good 63% yield. The reductive aromatization of the two cyclohexa-2,5-dienyl units in pro-Fc[6]CPP using SnCl2/HCl40 proceeded smoothly, and a pure sample of Fc[6]CPP could be isolated avoiding column chromatography in 76% yield. The final nanohoop Fc[6]CPP is soluble in dichloromethane and THF and displays high chemical stability when stored under ambient conditions over a few months as a solid. The structures of both macrocycles pro-Fc[6]CPP and Fc[6]CPP were confirmed by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry.

Scheme 1. Synthesis of Fc[6]CPP Conditions.

Scheme 1

Open in a new tab

Reaction conditions: (a) 1 (3 equiv), Pd(dppf)Cl2 (0.05 equiv), NaOH (4 equiv), DME/H2O, 85 °C, 20 h; (b) B2pin2 (4 equiv), Pd2(dba)3 (0.05 equiv), XPhos (0.2 equiv), KOAc (8 equiv), 1,4-dioxane, 110 °C, 16 h; (c) Pd(dppf)Cl2 (0.1 equiv), KF (1 equiv), B(OH)3 (5 equiv), THF/H2O, air, 40 °C, 20 h; and (d) H2SnCl4 (3.6 equiv), THF, RT, 2 h.

Single crystals were obtained by vapor diffusion of n-hexane into a toluene solution (20 °C) of pro-Fc[6]CPP and vapor diffusion of methanol into a THF solution (at 4 °C) of Fc[6]CPP. The X-ray diffraction analysis unequivocally confirmed their macrocyclic structure (Figure 2). Compound pro-Fc[6]CPP crystallized in the triclinic P–1 space group, and Fc fluxionality allowed it to adopt a triangular shape. Both enantiomers with opposite helicity (Figures S2 and S3) can be clearly distinguished in the crystal. Nanohoop Fc[6]CPP crystallized in the monoclinic P21 space group. Here, the Fc flexibility allowed the macrocycle to adopt an oval shape (Figure 2b) typical for meta-CPPs41 and related nanohoops.42,43 The size of the elliptic cavity is 12.6 Å in length and 7.0 Å in width. The connecting Cp carbon atoms in the Fc moiety are nearly eclipsed. Further analysis of the crystal structures revealed the effect of the strain imparted to Fc by the curvature of the macrocycles. The tilt angle α defined by the planes of the Cp rings and the Cp–Fe–Cp angle δ—common descriptors describing ferrocenophanes (see Figure S1)—differ in pro-Fc[6]CPP (Table S2) from the ideal values44 in unstrained Fc (α = 0°; δ = 180°) only slightly. On the other hand, the values determined for Fc[6]CPP (10.62°; 172.84°) clearly indicate that part of the total strain in the macrocycle has been transferred to Fc. The deviation from the ideal angles correlates with Estrain values of 13.7 and 82.6 kcal mol–1 calculated for both pro-Fc[6]CPP and Fc[6]CPP, respectively, using homodesmotic reactions (Scheme S1). The DFT-calculated geometries reproduce the crystal structures well, and the calculated strain in Fc[6]CPP approaches that of [7]CPP (Estrain = 84.0 kcal mol–1).45 Despite the significant strain, the Fc in Fc[6]CPP is markedly less distorted than less strained [1]- and [2]ferrocenophanes (14–31 kcal mol–1; α = 19–31° and δ = 156–167°).26,46−48 Although the strain energies in [n]ferrocenophanes and Fc[6]CPP markedly differ, the strain calculated per atom is comparable, which highlights its different distribution. The values of α and δ suggest that Fc in Fc[6]CPP is less strained than that in the known [n]ferrocenophanes. The large distortion of the Fc moiety in the latter compounds is known to weaken the Fe–Cp bond and to induce its cleavage upon irradiation. However, the Fc distortion observed for Fc[6]CPP matches that found in Fe(η-C5H4)2(CHCHCHCH) (10.2°; 173.08°),49 a compound known to be stable in air as a solid and in a solution,50 for which no photolytic processes are reported in the literature.

Figure 2.

Figure 2

Open in a new tab

X-ray crystal structures of (a) pro-Fc[6]CPP (selected conformer, see Supporting Information) and (b) Fc[6]CPP (thermal ellipsoids shown at 50% probability; all hydrogen atoms and solvent were omitted for clarity). The carbon atoms of one phenyl group in (b) are disordered over two sites with relative occupancies of 0.602:0.398.

We examined whether embedding an Fc unit into a strained macrocyclic structure affected the optical and redox properties. The latter were determined for CH2Cl2 solutions of Fc[6]CPP with 0.1 M [n-Bu4N][PF6] as a supporting electrolyte using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). A single anodic wave could be observed for Fc[6]CPP (Figures S7 and S8) with only a minor shift in the half-wave oxidation potential by ca. −50 mV with respect to the Fc/Fc+ couple. The Randles–Ševčík analysis revealed full reversibility of the oxidation process at the electrode (Figure S9). We then recorded the absorption spectra of Fc[6]CPP and pro-Fc[6]CPP (Figure 3 and Table 1). Nanohoop Fc[6]CPP exhibits a characteristic absorption profile observed for [n]CPPs with an intense transition at 330 nm (ε = 5.2 × 104 M–1 cm–1) and a distinct band at ∼400 nm, which corresponds to the S0 → S1 transition in CPPs. A weak solvatochromism is observed for Fc[6]CPP (Figure S10). Comparison to the absorption spectrum of pro-Fc[6]CPP, in which the conjugation in the macrocycle is interrupted by the pro-aromatic cyclohexa-2,5-dienyls, suggests that an unresolved low-energy transition (>450 nm) may exist in Fc[6]CPP. This is supported by TD–DFT calculations that predict that nearly degenerate Fc-centered transitions with a low oscillatory strength represent the lowest excited states in Fc[6]CPP. Indeed, such d–d transitions are clearly visible at 442 nm (ε = 90 M–1 cm–1) in Fc.51,52 Their slight bathochromic shift with the corresponding increase of ε in Fc[6]CPP is the consequence of extending the π-system of the Cp ligands and decreasing the overall symmetry of the chromophore, partially allowing the d–d transitions as shown by the natural transition orbitals analysis of the first seven transitions in Fc[6]CPP (see the Supporting Information). Despite the presence of the curved para-phenylene segment, Fc[6]CPP displays no luminescence. This confirms that the lowest-energy excited state in both pro-Fc[6]CPP and Fc[6]CPP is localized on the Fc moiety, which is a known luminescence quencher.

Figure 3.

Figure 3

Open in a new tab

UV/vis absorption spectra of Fc, pro-Fc[6]CPP, and Fc[6]CPP in PhCN. For the sake of comparison, the spectra of Fc and pro-Fc[6]CPP were scaled by a factor of 100 and 10, respectively.

Table 1. Summary of Photophysical, Redox and Structural Properties.

Compd. λabs (nm) εa (103 M–1 cm–1) E1/2 (mV) Estrainb (kcal mol–1) Φc (%)
Fc 442 0. 1 0.0 0.0 (1.5 ± 0.3) × 10–3
pro-Fc[6]CPP 463 0. 9 - 13.7 (4.9 ± 0.4) × 10–3
Fc[6]CPP 330 52, 2.3d –42e, –57f 82.6 6.0 ± 0.5
Open in a new tab
a

At maximum λabs.

b

At D3-B3LYP/6–31++g(d)/LanL2DZ(Fe) level of theory; see the Supporting Information for the computational details.

c

Absolute quantum yield of [Fe(phen)3]2+ formation in PhCN with 500 equiv of phen.

d

At λabs = 472 nm.

e

Determined by CV.

f

Determined by DPV.

Interestingly, while the absorption spectrum of Fc[6]CPP in toluene (c ≈ 20 μM) did not change upon exposure to ambient light (96 h, Figure S11), an equally concentrated sample of Fc[6]CPP in polar PhCN displayed a notable change in color within dozens of minutes. The photolysis rate is rapid when green light (λLED = 525 ± 18 nm, >10 mW) is used as the light source and the characteristic CPP band at 330 nm is no longer discernible after 30 min of irradiation (Figure S12). Note that Fc[6]CPP remains stable in the dark for >24 h at room temperature (Figure 4a). Similar experiments with samples of pro-Fc[6]CPP or Fc revealed a striking difference among the compounds. Both pro-Fc[6]CPP and Fc in PhCN are stable over days when exposed to daylight (Figures S13 and S14). Based on the known cases of Fe–Cp bond dissociation triggered by irradiation16,23−27 or mechanical force,28–30 we hypothesized that Fc[6]CPP might undergo a macrocyclic ring-opening, eventually releasing the Fe2+ ion and the substituted p-sexiphenyl (Figure 1b). To test this hypothesis, the solution of Fc[6]CPP was exposed to ambient light in the presence of 500 equiv of 1,10-phenanthroline (phen), which is known to bind Fe2+ ion to form ferroin, [Fe(phen)3]2+ complex with a distinct absorption spectrum. After 24 h, the solution was filtered, and its absorption spectrum matched that of the independently prepared sample of [Fe(phen)3]2+ (Figure 4b). The nature of the complex was also confirmed by mass spectrometry (Figure S15). Besides the photoinduced release and subsequent catch of Fe2+ from the nanohoop, we observed the formation of a precipitate that likely corresponds to the released p-sexiphenyl derivative. However, we have not yet been able to unequivocally identify the structure of the latter by mass spectrometry. We determined the yield of [Fe(phen)3]2+ formation by absorption spectroscopy (see Supporting Information) to be (80 ± 3.0) and (67 ± 5.2) % before and after filtration of the photolyzed solution, respectively. The difference stems from the presence of the precipitate, which leads to slight scattering at the absorption band of [Fe(phen)3]2+. The control experiments conducted at room temperature in the dark with a large excess of phen (500 equiv) showed minor [Fe(phen)3]2+ formation (<10% after 24 h, unfiltered, Figure S17). However, increasing the temperature to 70 °C resulted in a markedly faster transformation (Figure S18), although the reaction required a few days to reach full conversion. These observations strongly support our assumption that the strain perturbing the Fc structure markedly affects the reactivity of Fc in Fc[6]CPP.

Figure 4.

Figure 4

Open in a new tab

(a) Fc[6]CPP in PhCN (c ≈ 20 μM) stirred in dark (solid line) or in ambient light (dashed line) and (b) normalized absorption spectra of Fc[6]CPP in PhCN (c ≈ 60 μM, phen: 500 equiv) stirred in ambient light for 24 h (red: unfiltered, light red: filtered) and independently prepared [Fe(phen)3]2+ (blue). The spectrum at 0 h (dark red) was scaled to match the ε of [Fe(phen)3]2+.

To quantify the reactivity of Fc[6]CPP, we compared its photochemical behavior with the less strained precursor pro-Fc[6]CPP as well as the unstrained Fc itself. For this purpose, we measured the absolute quantum yields of [Fe(phen)3]2+ formation in PhCN for all three compounds (Φ, Table 1) under identical conditions (c = 40 μM, 500 equiv of phen, λLED = 472 nm). The large excess of phen was necessary to detect appreciable amounts of [Fe(phen)3]2+ formed from both pro-Fc[6]CPP and Fc within hours at the full intensity of our LED source (130 mW), while Fc[6]CPP could be converted in seconds. Comparison of the measured Φs reveals the striking enhancement of the reactivity of Fc[6]CPP. While the determined Φs for Fc and pro-Fc[6]CPP are (1.5 ± 0.3) × 10–5 and (4.9 ± 0.4) × 10–5, respectively, the ring-opening in Fc[6]CPP is >1000-fold more efficient. The value of Φ reflects the Fc tilt angle and the strain energy in the individual compounds (Table 1), but it also depends strongly on the concentration of the phen ligand (Figure 5). The quantum yield for Fc[6]CPP grew from 1.6 × 10–3 to 0.06 with an increasing amount of phen. The Φ levels off at a large excess of phen and reaches a limiting value that compares favorably to the intersystem crossing quantum yield reported for Fc (ΦISC = 0.085).53 It suggests that the Fe–Cp bond dissociation occurs by intercepting the excited Fc unit by a ligand molecule. This step may take place efficiently only in 3Fc that possesses a sufficiently long excited state lifetime (τ (3Fc) = 90 ns vs τ (1Fc) = 10 ps).53 A simulation of the expected Φ of [Fe(phen)3]2+ formation via a triplet state, while accounting for the quenching of the oxygen present in the solution, matches the observed concentration dependence well (Figure 5). Comparison of the Φs determined in the presence and absence of oxygen with 10 equiv of phen in the solution showed a statistically significant difference (t(6) = 2.26, p < 0.05), confirming that the reaction occurs via the triplet state of Fc[6]CPP. Indeed, the DFT-calculated spin density shows an antibonding character of the Fe–Cp bond in triplet Fc[6]CPP and the presence of an electron hole at the Fe center (Figure S35). This increases iron electrophilicity47,54 promoting the bond dissociation when attacked by a nucleophilic solvent or external ligand.16 Such a polar transition state is in agreement with our observation that the photolysis of Fc[6]CPP is facile in polar PhCN (Figure 4a) and inefficient in toluene (Figure S11). It has also been reported that electron-donating solvents promote the Fe–Cp bond dissociation.25,55−57 We thus expect that a half-sandwich complex 7 (Scheme 2) is formed as the first reaction step with a temporarily coordinated solvent and the p-sexiphenyl ligand still attached to the Fe via the remaining Cp. Subsequently, excess phen must rapidly replace the labile ligands because we do not observe the formation of any intermediates by UV–vis spectroscopy with 250 ms sampling. A complex such as 7 has often been proposed58−60 as an intermediate in the dissociation of [1]- and [2]ferrocenophanes, but it has never been detected. Note that no free Fe2+ forms directly from Fc[6]CPP, which we verified by photolysis of the Fc[6]CPP before the addition of phen (500 equiv) to the PhCN solution. Here, we observed only a slow formation (>72 h) of [Fe(phen)3]2+ in the dark. The process proceeded somewhat faster under ambient light. However, complexation of Fe(OTf)2 in PhCN treated with excess phen occurs rapidly (<10 min, compare Figures S29–S31).

Figure 5.

Figure 5

Open in a new tab

Measured (red, with standard deviation) and simulated (black, see the Supporting Information for details) quantum yields of [Fe(phen)3]2+ formation from Fc[6]CPP in PhCN upon irradiation with a 472 nm LED as a function of phen concentration.

Scheme 2. Proposed Mechanism for Dissociation in the Presence of Phen of Fc[6]CPP upon Irradiation.

Scheme 2

Open in a new tab

As shown above, Fc[6]CPP undergoes a remarkably clean ring-opening reaction in a polar environment upon irradiation with benign light. The elevated strain energy of the nanohoop makes photochemical Fe–Cp bond dissociation and subsequent Fe2+ release and trapping particularly efficient. Given the crucial role of iron in various biological processes, we decided to probe the photoreactivity of Fc[6]CPP in a mixed aqueous/organic medium due to the negligible solubility of the nanohoop in pure water. The irradiation of Fc[6]CPP in a mixture of H2O/THF (v/v = 1:1, 500 equiv phen) with green light resulted in the formation of [Fe(phen)3]2+. Here, [Fe(phen)3]2+ formed cleanly in (81 ± 1.1) % yield after filtration (Figure S33) with ∼75% efficiency compared to the experiment in neat PhCN. The iron release from Fc[6]CPP upon irradiation is thus a highly effective process also in polar protic solvents, which creates exciting opportunities for biological applications such as delivery and dosing of iron controlled by light, e.g., to study their biochemical pathways or to induce ferroptosis.61−63 It is important to note here that although the macrocyclic structure of Fc[6]CPP irreversibly opens upon irradiation without phen, the presence of phen alters the iron release mechanism and significantly enhances the overall release rate. The nature and the kinetic stability of the formed primary complex in water in the absence of phen require detailed mechanistic scrutiny to reveal how it might be decomposed to release iron using nucleophiles ubiquitous in biological systems.

The tunability of strain in carbon nanohoops by precision synthesis may represent a great tool to uncover and control the reactivity in similar types of metallamacrocycles such as the one designed in this work, which could aid the development of new redox-active or supramolecular systems that are responsive to light or mechanical force. Work along these lines is currently ongoing in our laboratories.

Conclusions

In summary, we synthesized a highly strained π-conjugated macrocycle Fc[6]CPP that incorporates ferrocene. Its structure was unequivocally characterized by X-ray diffraction analysis and quantum chemical calculations. The high strain in Fc[6]CPP transforms the reactivity of photostable ferrocene into a photoactivatable carrier of iron that is released via iron–cyclopentadienyl bond cleavage and easily trapped with phenanthroline to form a ferroin complex. The observed clean and high-yielding reaction is 3 orders of magnitude more efficient than that for ferrocene and demonstrates the power of molecular strain to uncover and control the reactivity of an otherwise stable metallocene complex. Furthermore, we demonstrated that this system efficiently releases iron in a mixed aqueous/organic environment, suggesting that its operation can be translated to a biological context. We believe that this work will thus motivate new developments in the fields of responsive materials, photocages, or organometallic and host–guest chemistry.

Acknowledgments

This work was supported by the European Research Council (ERC, Grant Agreement No. 949397). P.Š. acknowledges the Swiss National Science Foundation for funding (PZ00P2_193425).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.4c15818.

  • Experimental procedures and characterization data for all new compounds; experimental and computational details (PDF)

The authors declare no competing financial interest.

Supplementary Material

ja4c15818_si_001.pdf (3.6MB, pdf)

References

  1. Eaton W. A.; Henry E. R.; Hofrichter J.; Mozzarelli A. Is Cooperative Oxygen Binding by Hemoglobin Really Understood?. Nat. Struct. Biol. 1999, 6 (4), 351–358. 10.1038/7586. [DOI] [PubMed] [Google Scholar]
  2. Aisen P.; Enns C.; Wessling-Resnick M. Chemistry and Biology of Eukaryotic Iron Metabolism. Int. J. Biochem. Cell Biol. 2001, 33 (10), 940–959. 10.1016/S1357-2725(01)00063-2. [DOI] [PubMed] [Google Scholar]
  3. Liu J.; Chakraborty S.; Hosseinzadeh P.; Yu Y.; Tian S.; Petrik I.; Bhagi A.; Lu Y. Metalloproteins Containing Cytochrome, Iron–Sulfur, or Copper Redox Centers. Chem. Rev. 2014, 114 (8), 4366–4469. 10.1021/cr400479b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Nordlund P.; Reichard P. Ribonucleotide Reductases. Annu. Rev. Biochem. 2006, 75, 681–706. 10.1146/annurev.biochem.75.103004.142443. [DOI] [PubMed] [Google Scholar]
  5. Nandi A.; Yan L.-J.; Jana C. K.; Das N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxid. Med. Cell. Longev. 2019, 2019, 9613090. 10.1155/2019/9613090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Galaris D.; Barbouti A.; Pantopoulos K. Iron Homeostasis and Oxidative Stress: An Intimate Relationship. Biochim. Biophys. Acta, Mol. Cell Res. 2019, 1866 (12), 118535. 10.1016/j.bbamcr.2019.118535. [DOI] [PubMed] [Google Scholar]
  7. Kovaleva E. G.; Lipscomb J. D. Versatility of Biological Non-Heme Fe(II) Centers in Oxygen Activation Reactions. Nat. Chem. Biol. 2008, 4 (3), 186–193. 10.1038/nchembio.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Rouault T. A. Iron Metabolism in the CNS: Implications for Neurodegenerative Diseases. Nat. Rev. Neurosci. 2013, 14 (8), 551–564. 10.1038/nrn3453. [DOI] [PubMed] [Google Scholar]
  9. Kim J.; Wessling-Resnick M. Iron and Mechanisms of Emotional Behavior. J. Nutr. Biochem. 2014, 25 (11), 1101–1107. 10.1016/j.jnutbio.2014.07.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. De Domenico I.; McVey Ward D.; Kaplan J. Regulation of Iron Acquisition and Storage: Consequences for Iron-Linked Disorders. Nat. Rev. Mol. Cell Biol. 2008, 9 (1), 72–81. 10.1038/nrm2295. [DOI] [PubMed] [Google Scholar]
  11. Wessling-Resnick M. Iron Homeostasis and the Inflammatory Response. Annu. Rev. Nutr. 2010, 30, 105–122. 10.1146/annurev.nutr.012809.104804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marques O.; Weiss G.; Muckenthaler M. U. The Role of Iron in Chronic Inflammatory Diseases: From Mechanisms to Treatment Options in Anemia of Inflammation. Blood 2022, 140 (19), 2011–2023. 10.1182/blood.2021013472. [DOI] [PubMed] [Google Scholar]
  13. Pietrangelo A.; Trautwein C. Mechanisms of Disease: The Role of Hepcidin in Iron Homeostasis—Implications for Hemochromatosis and Other Disorders. Nat. Clin. Pract. Gastroenterol. Hepatol. 2004, 1 (1), 39–45. 10.1038/ncpgasthep0019. [DOI] [PubMed] [Google Scholar]
  14. Wilkinson G.; Rosenblum M.; Whiting M. C.; Woodward R. B. The Structure of Iron Bis-Cyclopentadienyl. J. Am. Chem. Soc. 1952, 74 (8), 2125–2126. 10.1021/ja01128a527. [DOI] [Google Scholar]
  15. Lewis K. E.; Smith G. P. Bond Dissociation Energies in Ferrocene. J. Am. Chem. Soc. 1984, 106 (16), 4650–4651. 10.1021/ja00328a077. [DOI] [Google Scholar]
  16. Tanabe M.; Vandermeulen G. W. M.; Chan W. Y.; Cyr P. W.; Vanderark L.; Rider D. A.; Manners I. Photocontrolled Living Polymerizations. Nat. Mater. 2006, 5 (6), 467–470. 10.1038/nmat1649. [DOI] [PubMed] [Google Scholar]
  17. Hailes R. L. N.; Oliver A. M.; Gwyther J.; Whittell G. R.; Manners I. Polyferrocenylsilanes: Synthesis, Properties, and Applications. Chem. Soc. Rev. 2016, 45 (19), 5358–5407. 10.1039/C6CS00155F. [DOI] [PubMed] [Google Scholar]
  18. Astruc D.; Ornelas C.; Ruiz Aranzaes J. Ferrocenyl-Terminated Dendrimers: Design for Applications in Molecular Electronics, Molecular Recognition and Catalysis. J. Inorg. Organomet. Polym. Mater. 2008, 18 (1), 4–17. 10.1007/s10904-007-9191-7. [DOI] [Google Scholar]
  19. Sun R.; Wang L.; Yu H.; Abdin Z.-.; Chen Y.; Huang J.; Tong R. Molecular Recognition and Sensing Based on Ferrocene Derivatives and Ferrocene-Based Polymers. Organometallics 2014, 33 (18), 4560–4573. 10.1021/om5000453. [DOI] [Google Scholar]
  20. Bernardo O.; González-Pelayo S.; López L. A. Synthesis and Applications of Ferrocene-Fused Nitrogen Heterocycles. Eur. J. Inorg. Chem. 2022, 2022 (8), e202100911 10.1002/ejic.202100911. [DOI] [Google Scholar]
  21. Rauf U.; Shabir G.; Bukhari S.; Albericio F.; Saeed A. Contemporary Developments in Ferrocene Chemistry: Physical, Chemical, Biological and Industrial Aspects. Molecules 2023, 28 (15), 5765. 10.3390/molecules28155765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roy G.; Gupta R.; Ranjan Sahoo S.; Saha S.; Asthana D.; Chandra Mondal P. Ferrocene as an Iconic Redox Marker: From Solution Chemistry to Molecular Electronic Devices. Coord. Chem. Rev. 2022, 473, 214816. 10.1016/j.ccr.2022.214816. [DOI] [Google Scholar]
  23. Mizuta T.; Onishi M.; Miyoshi K. Photolytic Ring-Opening Polymerization of Phosphorus-Bridged [1]Ferrocenophane Coordinating to an Organometallic Fragment. Organometallics 2000, 19 (24), 5005–5009. 10.1021/om000453c. [DOI] [Google Scholar]
  24. Patra S. K.; Whittell G. R.; Nagiah S.; Ho C.-L.; Wong W.-Y.; Manners I. Photocontrolled Living Anionic Polymerization of Phosphorus-Bridged [1]Ferrocenophanes: A Route to Well-Defined Polyferrocenylphosphine (PFP) Homopolymers and Block Copolymers. Chem. – Eur. J. 2010, 16 (10), 3240–3250. 10.1002/chem.200902886. [DOI] [PubMed] [Google Scholar]
  25. Tanabe M.; Manners I. Photolytic Living Anionic Ring-Opening Polymerization (ROP) of Silicon-Bridged [1]Ferrocenophanes via an Iron-Cyclopentadienyl Bond Cleavage Mechanism. J. Am. Chem. Soc. 2004, 126 (37), 11434–11435. 10.1021/ja046657s. [DOI] [PubMed] [Google Scholar]
  26. Ieong N. S.; Chan W. Y.; Lough A. J.; Haddow M. F.; Manners I. Photoinduced Fe-Cp Bond Cleavage and Insertion Reactions of Strained Silicon- and Sulphur-Bridged [1]Ferrocenophanes in the Presence of Transition-Metal Carbonyls. Chem. Weinh. Bergstr. Ger. 2008, 14 (4), 1253–1263. 10.1002/chem.200700961. [DOI] [PubMed] [Google Scholar]
  27. Herbert D. E.; Mayer U. F. J.; Gilroy J. B.; López-Gómez M. J.; Lough A. J.; Charmant J. P. H.; Manners I. Photocontrolled Ring-Opening Polymerization of Strained Dicarba[2]Ferrocenophanes: A Route to Well-Defined Polyferrocenylethylene Homopolymers and Block Copolymers. Chem. – Eur. J. 2009, 15 (45), 12234–12246. 10.1002/chem.200901311. [DOI] [PubMed] [Google Scholar]
  28. Di Giannantonio M.; Ayer M. A.; Verde-Sesto E.; Lattuada M.; Weder C.; Fromm K. M. Triggered Metal Ion Release and Oxidation: Ferrocene as a Mechanophore in Polymers. Angew. Chem., Int. Ed. 2018, 57 (35), 11445–11450. 10.1002/anie.201803524. [DOI] [PubMed] [Google Scholar]
  29. Zhang Y.; Wang Z.; Kouznetsova T. B.; Sha Y.; Xu E.; Shannahan L.; Fermen-Coker M.; Lin Y.; Tang C.; Craig S. L. Distal Conformational Locks on Ferrocene Mechanophores Guide Reaction Pathways for Increased Mechanochemical Reactivity. Nat. Chem. 2021, 13 (1), 56–62. 10.1038/s41557-020-00600-2. [DOI] [PubMed] [Google Scholar]
  30. Sha Y.; Zhang Y.; Xu E.; Wang Z.; Zhu T.; Craig S. L.; Tang C. Quantitative and Mechanistic Mechanochemistry in Ferrocene Dissociation. ACS Macro Lett. 2018, 7 (10), 1174–1179. 10.1021/acsmacrolett.8b00625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Jasti R.; Bhattacharjee J.; Neaton J. B.; Bertozzi C. R. Synthesis, Characterization, and Theory of [9]-, [12]-, and [18]Cycloparaphenylene: Carbon Nanohoop Structures. J. Am. Chem. Soc. 2008, 130 (52), 17646–17647. 10.1021/ja807126u. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Segawa Y.; Yagi A.; Matsui K.; Itami K. Design and Synthesis of Carbon Nanotube Segments. Angew. Chem., Int. Ed. 2016, 55 (17), 5136–5158. 10.1002/anie.201508384. [DOI] [PubMed] [Google Scholar]
  33. Lan B.; Xu J.; Zhu L.; Chen X.; Kono H.; Wang P.; Zuo X.; Yan J.; Yagi A.; Zheng Y.; et al. Side-Chain Type Ferrocene Macrocycles. Precis. Chem. 2024, 2, 143. 10.1021/prechem.3c00121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zhu L.; Xu J.; Lan B.; Chen X.; Kono H.; Xu H.; Yan J.; Li W.; Yagi A.; Yuan Y.; Itami K.; Li Y. Ferrocene-Based Conjugated Macrocycles: Shotgun Synthesis, Size-Dependent Properties and Tunable Fluorescence Intensity. Org. Chem. Front. 2024, 11 (18), 5130–5137. 10.1039/D4QO01079E. [DOI] [Google Scholar]
  35. Kubota N.; Segawa Y.; Itami K. η 6 -Cycloparaphenylene Transition Metal Complexes: Synthesis, Structure, Photophysical Properties, and Application to the Selective Monofunctionalization of Cycloparaphenylenes. J. Am. Chem. Soc. 2015, 137 (3), 1356–1361. 10.1021/ja512271p. [DOI] [PubMed] [Google Scholar]
  36. Kayahara E.; Patel V. K.; Mercier A.; Kündig E. P.; Yamago S. Regioselective Synthesis and Characterization of Multinuclear Convex-Bound Ruthenium-[n]Cycloparaphenylene (N = 5 and 6) Complexes. Angew. Chem., Int. Ed. 2016, 55 (1), 302–306. 10.1002/anie.201508003. [DOI] [PubMed] [Google Scholar]
  37. Van Raden J. M.; Louie S.; Zakharov L. N.; Jasti R. 2,2′-Bipyridyl-Embedded Cycloparaphenylenes as a General Strategy To Investigate Nanohoop-Based Coordination Complexes. J. Am. Chem. Soc. 2017, 139 (8), 2936–2939. 10.1021/jacs.7b00359. [DOI] [PubMed] [Google Scholar]
  38. Ojea M. J. H.; Raden J. M. V.; Louie S.; Collins R.; Pividori D.; Cirera J.; Meyer K.; Jasti R.; Layfield R. A. Spin-Crossover Properties of an Iron(II) Coordination Nanohoop. Angew. Chem., Int. Ed. 2021, 60 (7), 3515–3518. 10.1002/anie.202013374. [DOI] [PubMed] [Google Scholar]
  39. Darzi E. R.; White B. M.; Loventhal L. K.; Zakharov L. N.; Jasti R. An Operationally Simple and Mild Oxidative Homocoupling of Aryl Boronic Esters To Access Conformationally Constrained Macrocycles. J. Am. Chem. Soc. 2017, 139 (8), 3106–3114. 10.1021/jacs.6b12658. [DOI] [PubMed] [Google Scholar]
  40. Patel V. K.; Kayahara E.; Yamago S. Practical Synthesis of [n]Cycloparaphenylenes (N = 5, 7–12) by H2SnCl4-Mediated Aromatization of 1,4-Dihydroxycyclo-2,5-Diene Precursors. Chem. – Eur. J. 2015, 21 (15), 5742–5749. 10.1002/chem.201406650. [DOI] [PubMed] [Google Scholar]
  41. Lovell T. C.; Colwell C. E.; Zakharov L. N.; Jasti R. Symmetry Breaking and the Turn-on Fluorescence of Small, Highly Strained Carbon Nanohoops. Chem. Sci. 2019, 10 (13), 3786–3790. 10.1039/C9SC00169G. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Li P.; Sisto T. J.; Darzi E. R.; Jasti R. The Effects of Cyclic Conjugation and Bending on the Optoelectronic Properties of Paraphenylenes. Org. Lett. 2014, 16 (1), 182–185. 10.1021/ol403168x. [DOI] [PubMed] [Google Scholar]
  43. Evans P. J.; Zakharov L. N.; Jasti R. Synthesis of Carbon Nanohoops Containing Thermally Stable Cis Azobenzene. J. Photochem. Photobiol. Chem. 2019, 382, 111878. 10.1016/j.jphotochem.2019.111878. [DOI] [Google Scholar]
  44. Dunitz J. D.; Orgel L. E.; Rich A. The Crystal Structure of Ferrocene. Acta Crystallogr. 1956, 9 (4), 373–375. 10.1107/S0365110X56001091. [DOI] [Google Scholar]
  45. Segawa Y.; Omachi H.; Itami K. Theoretical Studies on the Structures and Strain Energies of Cycloparaphenylenes. Org. Lett. 2010, 12 (10), 2262–2265. 10.1021/ol1006168. [DOI] [PubMed] [Google Scholar]
  46. Foucher D. A.; Tang B. Z.; Manners I. Ring-Opening Polymerization of Strained, Ring-Tilted Ferrocenophanes: A Route to High-Molecular-Weight Poly(Ferrocenylsilanes). J. Am. Chem. Soc. 1992, 114 (15), 6246–6248. 10.1021/ja00041a053. [DOI] [Google Scholar]
  47. Rulkens R.; Gates D. P.; Balaishis D.; Pudelski J. K.; McIntosh D. F.; Lough A. J.; Manners I. Highly Strained, Ring-Tilted [1]Ferrocenophanes Containing Group 16 Elements in the Bridge: Synthesis, Structures, and Ring-Opening Oligomerization and Polymerization of [1]Thia- and [1]Selenaferrocenophanes. J. Am. Chem. Soc. 1997, 119 (45), 10976–10986. 10.1021/ja972043u. [DOI] [Google Scholar]
  48. Khozeimeh Sarbisheh E.; Bhattacharjee H.; Cao M. P. T.; Zhu J.; Müller J. How Strained Are [1]Ferrocenophanes?. Organometallics 2017, 36 (3), 614–621. 10.1021/acs.organomet.6b00808. [DOI] [Google Scholar]
  49. Erickson M. S.; Fronczek F. R.; McLaughlin M. L. Synthesis of 1,4-(1,1′-Ferrocenediyl)-1,3-Butadiene: A Dieno-Ferrocenophane. Tetrahedron Lett. 1993, 34 (2), 197–198. 10.1016/S0040-4039(00)60545-2. [DOI] [Google Scholar]
  50. Pudelski J. K.; Callstrom M. R. Structure, Reactivity, and Electronic Properties of [4]Ferrocenophanes and [4]Ruthenocenophanes Prepared via a Novel Heteroannular Cyclization Reaction. Organometallics 1994, 13 (8), 3095–3109. 10.1021/om00020a026. [DOI] [Google Scholar]
  51. Gordon K. R.; Warren K. D. Spectroscopic and Magnetic Studies of the 3d Metallocenes. Inorg. Chem. 1978, 17 (4), 987–994. 10.1021/ic50182a038. [DOI] [Google Scholar]
  52. Yamaguchi Y.; Ding W.; Sanderson C. T.; Borden M. L.; Morgan M. J.; Kutal C. Electronic Structure, Spectroscopy, and Photochemistry of Group 8 Metallocenes. Coord. Chem. Rev. 2007, 251 (3–4), 515–524. 10.1016/j.ccr.2006.02.028. [DOI] [Google Scholar]
  53. Scuppa S.; Orian L.; Dini D.; Santi S.; Meneghetti M. Nonlinear Absorption Properties and Excited State Dynamics of Ferrocene. J. Phys. Chem. A 2009, 113 (33), 9286–9294. 10.1021/jp9047192. [DOI] [PubMed] [Google Scholar]
  54. Barlow S.; Drewitt M. J.; Dijkstra T.; Green J. C.; O’Hare D.; Whittingham C.; Wynn H. H.; Gates D. P.; Manners I.; Nelson J. M.; Pudelski J. K. Electronic Structure of Strained Silicon- and Sulfur-Bridged [1]Ferrocenophanes and an Analogous Dicarbon-Bridged [2]Ferrocenophane: An Investigation by Photoelectron Spectroscopy and Density-Functional Theory. Organometallics 1998, 17 (10), 2113–2120. 10.1021/om980087l. [DOI] [Google Scholar]
  55. Mizuta T.; Imamura Y.; Miyoshi K.; Yorimitsu H.; Oshima K. Phosphorus-Bridged [1.1]Ferrocenophane with Syn and Anti Conformations. Organometallics 2005, 24 (5), 990–996. 10.1021/om049155w. [DOI] [Google Scholar]
  56. Imamura Y.; Kubo K.; Mizuta T.; Miyoshi K. Reactions of Ring-Slipped Iron Complexes Derived from P(S)Ph-Bridged [1]Ferrocenophane: Synthesis of Bis(Half-Sandwich) Heterodinuclear Complexes. Organometallics 2006, 25 (9), 2301–2307. 10.1021/om060020v. [DOI] [Google Scholar]
  57. Herbert D. E.; Tanabe M.; Bourke S. C.; Lough A. J.; Manners I. Strain-Controlled, Photochemically, or Thermally Promoted Haptotropic Shifts of Cyclopentadienyl Ligands in Group 8 Metallocenophanes. J. Am. Chem. Soc. 2008, 130 (12), 4166–4176. 10.1021/ja077334+. [DOI] [PubMed] [Google Scholar]
  58. Mizuta T.; Imamura Y.; Miyoshi K. Ring-Opening Reaction of Phosphorus-Bridged [1]Ferrocenophane via Ring Slippage from η 5 - to η-Cp. J. Am. Chem. Soc. 2003, 125 (8), 2068–2069. 10.1021/ja029297m. [DOI] [PubMed] [Google Scholar]
  59. Chan W. Y.; Lough A. J.; Manners I. Organometallic Macrocycles and Cyclic Polymers by the Bipyridine-Initiated Photolytic Ring Opening of a Silicon-Bridged [1]Ferrocenophane. Angew. Chem., Int. Ed. 2007, 46 (47), 9069–9072. 10.1002/anie.200703430. [DOI] [PubMed] [Google Scholar]
  60. Herbert D. E.; Gilroy J. B.; Chan W. Y.; Chabanne L.; Staubitz A.; Lough A. J.; Manners I. Redox-Active Metallomacrocycles and Cyclic Metallopolymers: Photocontrolled Ring-Opening Oligomerization and Polymerization of Silicon-Bridged [1]Ferrocenophanes Using Substitutionally-Labile Lewis Bases as Initiators. J. Am. Chem. Soc. 2009, 131 (41), 14958–14968. 10.1021/ja904928c. [DOI] [PubMed] [Google Scholar]
  61. Chen J.; Guo Z.; Wang H.-B.; Zhou J.-J.; Zhang W.-J.; Chen Q.-W. Multifunctional Mesoporous Nanoparticles as pH-Responsive Fe2+ Reservoirs and Artemisinin Vehicles for Synergistic Inhibition of Tumor Growth. Biomaterials 2014, 35 (24), 6498–6507. 10.1016/j.biomaterials.2014.04.028. [DOI] [PubMed] [Google Scholar]
  62. Li Z.; Wu X.; Wang W.; Gai C.; Zhang W.; Li W.; Ding D. Fe(II) and Tannic Acid-Cloaked MOF as Carrier of Artemisinin for Supply of Ferrous Ions to Enhance Treatment of Triple-Negative Breast Cancer. Nanoscale Res. Lett. 2021, 16 (1), 37. 10.1186/s11671-021-03497-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Yang Y.; Tian Q.; Wu S.; Li Y.; Yang K.; Yan Y.; Shang L.; Li A.; Zhang L. Blue Light-Triggered Fe2+-Release from Monodispersed Ferrihydrite Nanoparticles for Cancer Iron Therapy. Biomaterials 2021, 271, 120739. 10.1016/j.biomaterials.2021.120739. [DOI] [PubMed] [Google Scholar]

Associated Data

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

Supplementary Materials

ja4c15818_si_001.pdf (3.6MB, pdf)

Articles from Journal of the American Chemical Society are provided here courtesy of American Chemical Society

RESOURCES