Inorganic Chemistry Frontiers Blog

We are delighted to highlight the following highly cited review articles published in Inorganic Chemistry Frontiers since 2023. We hope you enjoy reading them.

	MOF nanozymes: active sites and sensing applications Ziyan Zhang, Yujie Li, Zhishuang Yuan, Lingxia Wu, Jiping Ma, Weiqiang Tan, Yingjie Sun, Guangyao Zhang and Huining Chai   Inorg. Chem. Front., 2025,12, 400-429 https://doi.org/10.1039/D4QI02555E
	Porphyrin-based MOFs for photocatalysis in water: advancements in solar fuels generation and pollutants degradation Fangbing Liu, Irene Rincón, Herme G. Baldoví, Amarajothi Dhakshinamoorthy, Patricia Horcajada, Sara Rojas, Sergio Navalón and Alexandra Fateeva Inorg. Chem. Front., 2024,11, 2212-2245 https://doi.org/10.1039/D3QI01996A
	Recent progress on modulating luminescence thermal quenching properties of Bi3+-activated phosphors Xiang Lv, Ran Xiao, Jianxia Liu, Chunwei Yang, Yanmei Xin and Ning Guo Inorg. Chem. Front., 2024,11, 1668-1682 https://doi.org/10.1039/D3QI02588H
	Recent advancements in graphitic carbon nitride based direct Z- and S-scheme heterostructures for photocatalytic H2O2 production Subrat Kumar Sahoo, Lopamudra Acharya, Lijarani Biswal, Priyanka Priyadarshinia and Kulamani Parida Inorg. Chem. Front., 2024,11, 4914-4973 https://doi.org/10.1039/D4QI00950A
	Rational design of local microenvironment for electrocatalytic water splitting Xiang Li, Wangchuan Zhu, Yanqun Zhang, Yueyue Zhao, Danjun Wang, Yanzhong Zhen, Feng Fu and Chunming Yang Inorg. Chem. Front., 2024,11, 4080-4106 https://doi.org/10.1039/D4QI00854E
	Magneto-chiral dichroism of chiral lanthanide complexes Fabrice Pointillart, Matteo Atzori and Cyrille Train Inorg. Chem. Front., 2024,11, 1313-1321 https://doi.org/10.1039/D3QI02510A
	Research progress of MXenes and layered double hydroxides for supercapacitors Zhongtai Lin, Xue Li, Hao Zhang, Ben Bin Xu, Priyanka Wasnik, Handong Li, Man Vir Singh, Yong Ma, Tingxi Li and Zhanhu Guo Inorg. Chem. Front., 2023,10, 4358-4392 https://doi.org/10.1039/D3QI00819C
	Recent progress and strategies on the design of catalysts for electrochemical ammonia synthesis from nitrate reduction Wei Song, Luchao Yue, Xiaoya Fan, Yongsong Luo, Binwu Ying, Shengjun Sun, Dongdong Zheng, Qian Liu, Mohamed S. Hamdye and Xuping Sun Inorg. Chem. Front., 2023,10, 3489-3514 https://doi.org/10.1039/D3QI00554B
	Mechanisms of Mg carbonates precipitation and implications for CO2 capture and utilization/storage Hellen S. Santos, Hoang Nguyen, Fabricio Venâncio, Durgaprasad Ramteke, Ron Zevenhovenc and Paivo Kinnunen Inorg. Chem. Front., 2023,10, 2507-2546 https://doi.org/10.1039/D2QI02482A
	Recent progress in polyoxometalate–viologen photochromic hybrids: structural design, photochromic mechanism, and applications Li Li, Yang-Tao Yu, Yang Hua, Xiao-Nan Li and Hong Zhang Inorg. Chem. Front., 2023,10, 1965-1985 https://doi.org/10.1039/D3QI00040K

 

To celebrate the Year of the Snake, we are delighted to highlight some of the most popular articles published in Inorganic Chemistry Frontiers by corresponding authors based in countries celebrating the Chinese New Year.

We hope you enjoy reading these articles and wish you a happy and prosperous year of the Snake.

	Achieving ultra-trace analysis and multi-light driven photodegradation toward phenolic derivatives via a bifunctional catalyst derived from a Cu(I)-complex-modified polyoxometalate Shuang Li, Bingqian Wang, Guocheng Liu, Xiaohui Li, Chang Sun, Zhong Zhang and Xiuli Wang Inorg. Chem. Front., 2024,11, 1561-1572 https://doi.org/10.1039/D3QI02513F
	PEO/Li1.25Al0.25Zr1.75(PO4)3 composite solid electrolytes for high-rate and ultra-stable all-solid-state lithium metal batteries with impregnated cathode modification Yongquan Zhang, Hongchang Gao, Jingshun Wang, Qingguo Chi, Tiandong Zhang, Changhai Zhang, Yu Feng, Yue Zhang, Dianxue Cao and Kai Zhu Inorg. Chem. Front., 2024,11, 1289-1300 https://doi.org/10.1039/D3QI02407E
	Low-content Ru–Pt supported on oxygen vacancy enriched black TiO2 with strong electronic interactions as efficient hydrogen generation electrocatalysts Yuanzong Shen, Weichen Li, Wenna Wang, Liantao Xin, Weiping Xiao, Guangrui Xu, Dehong Chen, Lei Wang, Fusheng Liu and Zexing Wu Inorg. Chem. Front., 2024,11, 5508-5516 https://doi.org/10.1039/D4QI00919C
	Hierarchical mesoporous N-doped carbon as an efficient ORR/OER bifunctional electrocatalyst for rechargeable zinc–air battery Ping Li, Jinghong Wen, Yang Xiang, Meiqi Li, Yunxiu Zhao, Suna Wang, Jianmin Dou, Yunwu Li, Huiyan Ma and Liqiang Xu Inorg. Chem. Front., 2024,11, 5345-5358 https://doi.org/10.1039/D4QI00637B
	A chelating coordination modulation method for the synthesis of Ti-MOF single crystals Hui-Zi Li, Shangda Li, Fei Wang and Jian Zhang Inorg. Chem. Front., 2024,11, 2876-2883 https://doi.org/10.1039/D4QI00436A
	Optimized arrangement of non-π-conjugated PO3NH3 units leads to enhanced ultraviolet optical nonlinearity in NaPO3NH3 Lingli Wu, Haotian Tian, Chensheng Lin, Xin Zhao, Huixin Fan, Pengxiang Dong, Shunda Yang, Ning Ye and Min Luo Inorg. Chem. Front., 2024,11, 1145-1152 https://doi.org/10.1039/D3QI02465B
	Recent progress on modulating luminescence thermal quenching properties of Bi3+-activated phosphors Xiang Lv, Ran Xiao, Jianxia Liu, Chunwei Yang, Yanmei Xin and Ning Guo Inorg. Chem. Front., 2024,11, 1668-1682 https://doi.org/10.1039/D3QI02588H
	Covalent organic framework based photocatalysts for efficient visible-light driven hydrogen peroxide production Ke-Hui Xie, Guang-Bo Wang, Fei Zhao, Miao-Can Wang, Hao-Yu Zhang, Hao-Ran Ma, Zi-Zheng Chen, Lin Jiang, Yan Geng and Yu-Bin Dong Inorg. Chem. Front., 2024,11, 1322-1338 https://doi.org/10.1039/D3QI02391E
	Rational design of local microenvironment for electrocatalytic water splitting Xiang Li, Wangchuan Zhu, Yanqun Zhang, Yueyue Zhao, Danjun Wang, Yanzhong Zhen, Feng Fu and Chunming Yang Inorg. Chem. Front., 2024,11, 4080-4106 https://doi.org/10.1039/D4QI00854E
	Advancing biomedical applications of polyoxometalate-based metal–organic frameworks: from design to therapeutic potential Lijin Wang, Pengyu Dai, Hongli Ma, Tiedong Sun and Jinsong Peng Inorg. Chem. Front., 2024,11, 1339-1365 https://doi.org/10.1039/D3QI02414H

Molecular magnetism is a diverse field within chemistry with strong links to other disciplines across physical sciences. Current research focuses on magnetic memory and quantum information processing but also extends to medical diagnostics and catalysis. Here we highlight some of the exciting research on this topic that was recently published in Inorganic Chemistry Frontiers. Hope you find them enjoyable to read.

	Low-coordinate bis(imidazolin-2-iminato) dysprosium(III) single-molecule magnets Rong Sun, Chen Wang, Bing-Wu Wang, Zhe-Ming Wang, Yao-Feng Chen, Matthias Tamm and Song Gao Inorg. Chem. Front., 2023,10, 485-492 https://doi.org/10.1039/D2QI02180C
	Single-ion magnetism behaviors in lanthanide(III) based coordination frameworks Qingyun Wan, Masanori Wakizaka and Masahiro Yamashita Inorg. Chem. Front., 2023,10, 5212-5224 https://doi.org/10.1039/D3QI00925D
	Actinide-based single-molecule magnets: alone or in a group? Ming Liu, Xiao-Han Peng, Fu-Sheng Guo and Ming-Liang Tong Inorg. Chem. Front., 2023,10, 3742-3755 https://doi.org/10.1039/D3QI00523B
	The importance of second sphere interactions on single molecule magnet performance Brodie E. Matheson, Tyson N. Dais, Marryllyn E. Donaldson, Gareth J. Rowlands and Paul G. Plieger Inorg. Chem. Front., 2023,10, 6427-6439 https://doi.org/10.1039/D3QI01634J
	From unprecedented 2,2′-bisimidazole-bridged rare earth organometallics to magnetic hysteresis in the dysprosium congener Florian Benner and Selvan Demir Inorg. Chem. Front., 2023,10, 4981-4992 https://doi.org/10.1039/D3QI00546A

We welcome you to submit your next paper to Inorganic Chemistry Frontiers and contribute to the advancement of this fascinating field.

We are delighted to announce the establishment of our inaugural Early Career Advisory Board at Inorganic Chemistry Frontiers. This initiative aims to provide a direct channel for engaging with early-career researchers, supporting their professional development, and infusing our journal with fresh innovative perspectives from the younger generation.

We warmly invite you to nominate emerging investigators to the board or encourage your colleagues to self-nominate before 25 February 2024.  

Role of the Early Career Advisory Board

At Inorganic Chemistry Frontiers, we value the voices of early-career researchers. Joining the board, you will be part of a dynamic group of emerging investigators, helping shape the future of a leading inorganic chemistry journal and benefiting from networking opportunities with the journal’s Editorial and Advisory Board members.

Your insights will be invaluable as you provide feedback on the journal’s scientific standards, suggest emerging topics and researchers worth featuring, and contribute to promotional and visibility initiatives within your community.

Terms of Service

Normally, members of the Early Career Advisory Board will serve a term of two years, with an option for reappointment for a maximum of two consecutive terms.

Eligibility

• Nominations are open to researchers of any nationality from academia or industry.
• Candidates should typically be no more than 6 years from starting an independent research position (Assistant Professor or industry equivalent); appropriate consideration will be given to those who have taken a career break, followed a different career path or work in systems where their time period to independence may vary.
• Candidates should demonstrate a commitment to advancing inorganic chemistry through developing high-quality journals.

How to Nominate

Please email the following information to InorgChemFrontiersED@rsc.org for your nominations.

Self-nominations are very welcome. If you are interested in joining our Early Career Advisory Board, please provide:

• An up-to-date CV which highlights your engagements in academic activities (conferences participation etc.) and services to the wider community (journals, societies, etc.)
• Any supplementary materials, such as a brief supporting statement from an active Principal Investigator or contact information of references.

To nominate someone else, please provide:

• Candidate’s name, position, affiliation, website URL and contact details, along with a brief description of the candidate’s research contribution and community engagement
• Nominator’s name, position, affiliation and contact details
• Any supporting materials, such as an up-to-date CV of the candidate

Selection Criteria

Editorial Board of the journal will consider the following aspects of all nominations as appropriate:

• Profile within institute and/or community
• Involvement in community and advocacy activities
• Area and quality of research
• Motivation to join Early Career Advisory Board

We look forward to receiving your nominations!

Kind Regards,

Prof Song Gao 
Editor-in-Chief, Inorganic Chemistry Frontiers
Sun Yat-sen University and Peking University

Dr Wenjun Liu
Executive Editor, Inorganic Chemistry Frontiers
Royal Society of Chemistry

From unprecedented 2,2′-bisimidazole-bridged rare earth organometallics to magnetic hysteresis in the dysprosium congener

Florian Benner and Selvan Demir

Inorg. Chem. Front., 2023, 10, 4981-4992

https://doi.org/10.1039/D3QI00546A

Single-molecule magnets (SMMs) are molecules that show slow magnetic relaxation, originating from a bistable magnetic ground state with a thermal barrier to spin relaxation (U_eff). Remarkably, SMM can exhibit open magnetic hysteresis loops which correspond to retaining magnetic memory just like tiny bar magnets can. This property renders SMMs exciting for potential applications in high-density information storage, magnetic refrigeration, quantum computing and spintronics. Over the last years, the SMM field exploited mononuclear dysprosium metallocenium cations as spin carriers, where the well-defined coordination sphere imposed by cyclopentadienyl ligands strongly amplifies the easy axis of the dysprosium(III) ion. To date, synthetically accessible single-ion magnets operate at best slightly above the boiling temperature of liquid nitrogen (77 K).   Consequently, it was realized that lanthanide ions must be strongly coupled to one another to increase operating temperatures, ideally towards room temperature. To this end, the nature of the bridging ligand is vital and the exploration of new organic bridging ligands along with their utility in coupling lanthanide metallocene fragments is crucial. That knowledge will aid to devise design principles of SMMs with amplified magnetic coupling between lanthanide metallocene moieties.

Recently, the group of Selvan Demir at Michigan State University implemented the bridging ligand 2,2′-bisimidazole for the first time into rare earth and magnetochemistry, where this tetranitrogen ligand connects two metallocenium units (Figure 1). The synthesized series consists of three compounds comprising the diamagnetic yttrium, the paramagnetic gadolinium (isotropic) and paramagnetic dysprosium (anisotropic) ions. Excitingly, the dinuclear dysprosium complex features SMM behavior and on the timescale of magnetic hysteresis measurements, open hysteresis loops of up to 5 K. The half-filled f-electron valence shell for trivalent gadolinium ions allows quantification of the magnetic exchange coupling since the orbital singlet affords magnetic behavior that is free of complications arising from spin-orbit coupling. Thus, dc magnetic susceptibility measurements on the respective gadolinium complex revealed weak antiferromagnetic interaction between the metal ions. Due to its comparable ionic size, the yttrium analog served as a diamagnetic surrogate to the lanthanides, enabling the in-depth investigation of the electronic structure of these complexes via spectroscopic methods and density functional theory (DFT) calculations. In this way, absorption spectra were related to the underlying electronic structure of these complexes, revealing prevalent excitations from the predominantly ligand-based frontier orbitals into metal-based higher-lying orbitals. This provided also profound insight into the redox (in)activity of the bisimidazole bridge, which, in contrast to its annulated 2,2′-bisbenzimidazole analog, showed no reactivity towards reductants or oxidants. This was primarily ascribed to the title compounds lacking accessible ligand-based low-lying π* orbitals, unlike the opposite observation for the respective bisbenzimidazole counterparts. In sum, the fact that the bisimidazole ligand retains and enhances the single-ion anisotropy of the dysprosium ions while providing a wealth of substitution sites for future chemical modification renders this ligand system highly promising for the construction of higher nuclearity systems.

 

Corresponding Author:

Selvan Demir is an Assistant Professor of Chemistry at Michigan State University. She received a Dr. rer. nat. in Chemistry from the University of Cologne researching on scandium solid state chemistry with Prof. Gerd Meyer and scandium organometallic chemistry with Prof. William J. Evans at the University of California, Irvine. Subsequently, she was a Postdoctoral Scholar, where she conducted research on lanthanide-based single-molecule magnets and porous aromatic frameworks with Prof. Jeffrey R. Long at the University of California, Berkeley. Simultaneously, she explored the transuranics with Dr. David K. Shuh at the Lawrence Berkeley National Laboratory. Afterwards, she took up a junior professorship of inorganic chemistry at the University of Göttingen. Since 2019, she researches with her group at Michigan State University, on various areas surrounding the chemistry of the rare earth elements and actinides. Her research program has a strong emphasis on organometallic chemistry, small molecule activation, organic radicals, single-molecule magnets, qubits, bismuth chemistry, dibenzocyclooctatetraene chemistry, and lanthanide/actinide separations.

In recent years, derivatives of carbazole have been studied intensively with focus on their optical properties to scry for applicability as materials in OLEDs and OFETs. Fine tuning of the electronic properties of the materials was achieved by a large variety of substitution patterns both on the central nitrogen atom and the carbon periphery.

Recently, the group of Dr. Hinz (Karlsruhe Institute of Technology, Germany) has investigated a series of alkali metal carbazolides with bulky arenes in positions 1 and 8 of the carbazole scaffold (see Figure 1). The alkali metal complexes of the type [(Cbz)M] show visible fluorescence with emissions maxima in the range of 520 and 460 nm in dependence of the metal ion. Quantum yields of up to 29% in the solid state were measured for the rubidium derivative.

The electronic transitions were rationalised with the aid of TD-DFT calculations. Upon HOMO→LUMO+1 excitation, density shifts from the carbazole scaffold to the arenes in positions 1 and 8 and thus are intraligand transitions. The geometry of the complexes only change slightly upon excitation which enables the highly efficient fluorescence.

Coordination of additional toluene molecules to the alkali metal shifts the emission maximum to lower energy and enables a second emission band arising from an interligand excitation from the carbazole to a toluene molecule. The quantum yields for the complexes in toluene solution are even higher than in the solid state and reach 100% for the lithium complex.

Corresponding author:

Alexander Hinz studied chemistry in Rostock, Germany, and is currently a junior group leader at the Karlsruhe Institute of Technology. The work of the Hinz group is focused on molecular main group chemistry and devoted to the investigation of low-coordinated, but highly reactive compounds.

E-mail: alexander.hinz@kit.edu

Single-molecule magnets (SMMs) are molecules that retain the slow relaxation of their magnetization upon removal of an applied magnetic field, acting as magnets below a characteristic temperature known as the blocking temperature. Research in this field has recently focused on the use of radicals as ligands to enhance the performance of SMMs through the exchange coupling of the radical- and metal-based spins. The strong interaction between the spin of the radical with the unpaired electrons of a metal ion effectively suppresses the quantum tunneling of the magnetization (QTM) and fast spin relaxation pathways involving spin excited states, thus promoting a thermal relaxation pathway for magnetization reversal. The latter is particularly important when designing lanthanide (Ln) based SMMs as the core-like nature of the 4f orbitals makes magnetic coupling challenging and thus they tend to suffer from through-barrier relaxation of the magnetization (i.e., QTM, Raman and direct mechanisms).

To this day several attempts towards this direction have been made leading to the isolation of strongly coupled Ln SMMs with the N₂^•3--based family exhibiting very good magnetic performance. However, the rational incorporation of the N₂ species into complexes is a synthetic challenge and it does not offer any room for structural modification. For this reason, other radicals, such as tetrazines have been explored by the group of Prof. Muralee Murugesu of the University of Ottawa. In the past the researchers had successfully incorporated the 1,2,4,5-tetrazine radical anion (tz^•−) into tetranuclear “Ln₄” metallocenes which led to strong magnetic coupling and significant magnetic hysteresis (H_c = 3 T).

Recently, the researchers aimed to isolate a dinuclear building block so that the role of the bridging ligand in the overall magnetic coupling in Ln systems can be better understood. In further detail, they have utilized the high performing {Cp^*₂Ln^III}⁺ moieties and bridge them by employing the tz^•−_, leading to the isolation of a new family of radical-bridged Ln metallocenes: [(Cp^*₂Ln^III)₂(tz^•−)(THF)₂](BPh₄), (Ln = Gd (1), Tb (2), Dy (3); THF = tetrahydrofuran).

They showed that a strong magnetic coupling between the Ln^III ions and the tz^•− was achieved, revealing a J_Gd-rad = -7.2 cm^-1 for 1 which is even comparable to some N₂^•3- bridged SMMs. Due to this, both 2 and 3 displayed zero-field SMM behavior with slow relaxation of the magnetization and magnetic hysteresis.

Ab initio calculations verified the strong antiferromagnetic Ln-rad coupling and showed that the magnetic state of 2 and 3 can be interpreted as a “giant-spin” where the relaxation of the magnetization is related to changes in the magnetic state of the overall exchange-coupled system. The slow relaxation of these SMMs is mediated via thermally activated processes through the first excited KDs which correspond to an Ising-type ferrimagnetic spin configuration where the magnetic moments of the Ln^III ions are co-aligned while the magnetic moment of the radical points to the opposite direction.

The researchers believe that the results presented in this work will be helpful for future strategies on designing new lanthanide metal complexes employing radical ligands in the pursuit of new strongly-coupled zero field SMMs.

Corresponding author:

Prof. Muralee Murugesu received his PhD from the University of Karlsruhe in 2002 under the supervision of Prof. A. K. Powell. He undertook postdoctoral stays at the University of Florida (2003–2005) with Prof. G. Christou, and jointly at the University of California, Berkeley and the University of California, San Francisco under the supervision of Prof. J. R. Long and the Nobel Laureate Prof. S. Pruissner (2005–2006). In 2006, he joined the University of Ottawa as an assistant professor and since 2015 he is a full professor. Prof. Murugesu’s research focuses on the design and development of Single-Molecule Magnets, Metal-Organic Frameworks and High-Energy materials.

Advances in the coordination chemistry of multinuclear compounds have been exploited to drive the self-assembly of many new discrete metallo-supramolecular motifs. Due to the nature of the metal-ligand interactions, many of these systems have a dynamic character with reversible association and dissociation able to generate complex mixtures. Unveil such dynamic behaviours, it is a priority to fully understand, control and design their functional properties. Among metallo-supramolecular systems, lanthanide (Ln) based architectures attracts much attention due to their remarkable optical and magnetic properties. However, design and control of the final supramolecule is very challenging due to the inner nature of the 4f orbitals and consequent small ligand-field effects. There is, however, a steady variation of the effective ionic radius (EIR) across the series, the so called “lanthanide contraction”. Although the radii difference (ΔEIR) is quite small (ca. 0.20 Å between La³⁺ and Lu³⁺ and ca. 0.02 Å between two consecutive lanthanides), it can have important chemical consequences on the nature and features of supramolecular complexes.

Recently, a group headed by Marzio Rancan of ICMATE-CNR (Italy) and collaborators from the University of Padova (Italy) and Dortmund University (Germany) have demonstrated that ΔEIR strongly affects the kinetics of Ln ions exchange between preassembled quadruple-stranded [Ln₂L₄]^2– cages (Figure 1).

The process has been qualitatively and quantitatively characterized by time-dependent electrospray ionization mass spectrometry (ESI-MS). Mixing a series of two homonuclear [Ln^A₂L₄]²⁻ and [Ln^B₂L₄]²⁻ with increasing Ln³⁺ ΔEIR always leads to the formation of a statistical mixture of homo- and heteronuclear helicates due to the Ln exchange. All the studied systems have an equilibrium constant close to K = 4. The Ln³⁺ ΔEIR, hence, does not affect the thermodynamics of the process that is mainly governed by statistical factors and entropy-driven. On the other hand, they demonstrate that the rate of the dynamic ion exchange is Ln radius-dependent (Figure 1b). The kinetic constants of the forward and backward reactions revealed an exponential trend depending on the Ln³⁺ ΔEIR of the two homonuclear pre-assembled cages (Figure 1c): from the minimum to the maximum value of ΔEIR, the kinetic constants increase by three orders of magnitude. This fundamental study hints new tools and guidelines to study dynamic processes in metallo-supramolecular ensembles, and for the precise preparation and control of lanthanide-based mixed coordination-driven systems.

Corresponding author:

Marzio Rancan is a Research Fellow at ICMATE-CNR (Italy). He received his PhD in Molecular Sciences at the University of Padova in 2009. He did post-doctoral studies at CNR, University of Padova and spent one year in the Molecular Magnetism Group at The University of Manchester (UK).  His current research is focused on the synthesis and characterization of coordination-driven molecular and supramolecular architectures with functional properties. He is the author of about 60 articles.

WEBSITE: http://wwwdisc.chimica.unipd.it/FMNLab/index.html

ORCID: https://orcid.org/0000-0001-9967-5283

RESEARCHGATE: https://www.researchgate.net/profile/Marzio-Rancan

Cancer is a major health issue worldwide, and the development of innovative and effective drugs is an ultimate demand for research. Iron compounds have aroused a great interest in the search for new metal based chemotherapics, on account of their relatively low toxicity and their redox chemistry, exportable to physiological media.

Some ferrocene derivatives have shown a promising anticancer potential, with a strong activity mostly associated with Fe^II to Fe^III oxidation, leading to alteration of the cellular redox balance and subsequent production of toxic substances (reactive oxygen species, ROS). However, they provide a limited variability of the metal coordination set, and they need to be carefully formulated for in vivo applications due to a generally insufficient water solubility.

Since 2019, a series of cationic [Fe^IFe^I] complexes based on the [Fe₂Cp₂(CO)₂] core and comprising a vinyliminium bridging ligand have emerged as a novel class of potential chemotherapeutic agents. Thanks to the unique features of the bimetallic core, these complexes are easily prepared up to gram scale from a commercial precursor in a few synthetic steps. Remarkably, they are amphiphilic and appreciably water-soluble, and exhibit an antiproliferative activity against cancer cell lines which depends on the ligand substituents. The choice of the latter is virtually limitless, thanks to the generality of the synthetic procedure, and this feature allows to optimise physico-chemical properties for biological purposes. Different mechanisms, mainly ROS production but also protein interaction and weak DNA binding, may contribute to the mode of action of these dinuclear structures.

Recently, the group of Fabio Marchetti and co-workers have reported, for the first time, the conjugation of a ferrocenyl moiety with a diiron framework, as a strategy to obtain robust mixed-valence triiron compounds featured by a potent cytotoxicity and excellent selectivity towards cancer cell lines (i.e., IC₅₀ values in the low micromolar/nanomolar range on the cancer cell lines, and up to 35 times higher values on the nontumoral cells).

A combination of stability studies, electrochemical experiments, iron cellular uptake and targeted biological studies indicate that the cationic triiron complexes synergistically combine the redox behaviour of the ferrocenyl moiety with the amphiphilicity and the versatility of the diiron vinyliminium structure, and that their powerful activity arises from the ability to disrupt the redox homeostasis of tumour cells, through the overproduction of intracellular ROS and the alteration of the thioredoxin reductase, assessed on a synthetic dodecapeptide as a simplified model of the enzyme.

Corresponding Author:

Fabio Marchetti received his Degree in Industrial Chemistry from the University of Bologna in 1999 (summa cum laude), and the PhD in Chemistry from the same University in 2003. In 2006 he obtained a researcher position at the University of Pisa, and since October 2018 he has been Full Professor in the same University. FM has co-authored over 200 scientific publications on international journals, 2 book chapters and 2 international patents. His research interests regard the synthesis, the characterization and the properties of new transition metal compounds, and the metal-mediated activation of small organic molecules.

Zirconium-89 complexation chemistry is an important area of research in the context of developing radiolabelled proteins for applications in diagnostic positron emission tomography (PET) imaging. For this imaging technology, the metalloradionuclide ⁸⁹Zr⁴⁺ ion needs to be sequestered by a ligand to form a coordination complex that is thermodynamically, kinetically, and metabolically stable in biological systems. In this regard, desferrioxamine B (DFO), a natural bacterial siderophore, is one of the outstanding hexadentate linear chelator for zirconium-89, used in clinical trials with ⁸⁹ZrDFO-radiolabeled antibodies (mAbs). Nevertheless, preclinical studies have demonstrated that ⁸⁹ZrDFO-mAbs can suffer from dissociation and metal ion release in vivo resulting in partial bone uptake in mice which could be partially due to the incomplete coordination sphere around the metallic cation. Driven by the goal of increasing the stability of the ⁸⁹Zr⁴⁺ coordination complex toward demetallation in vivo, several groups around the world have explored the synthesis and coordination chemistry of novel multidentate chelates with coordination numbers from 6 to 8 but the development of heptadentate remained unexplored.

Recently, a collaborative work between the group of Prof. Dr Jason P. Holland (University of Zurich, Switzerland) and a team from the Institut Plurisdisciplinaire Hubert Curien (IPHC, CNRS, University of Strasbourg, France) have demonstrated that photoactivatable heptadentate chelates could be a new alternative for the ultra-fast, light-induced production of stable ⁸⁹Zr-mAbs in vivo (Figure 1). The researchers synthesise new chelates, used density functional theory to predict the thermodynamic stability, and studied the in vitro stability of the radiolabelled complexes to find the most promising candidate for in vivo application.

The researchers also selected the most stable complex (Zr-2) and produced ⁸⁹Zr-radiolabelled onartuzumab (the monoclonal antibody component of MetMAb^TM which binds to the human hepatocyte growth-factor receptor c-MET) using photoradiochemical methods. Finally, the pharmacokinetic profile and c-MET targeting was evaluated in vivo and ex vivo by using PET imaging and biodistribution studies in female athymic nude mice bearing subcutaneous MKN-45 human gastric cancer xenografts (Figure 2).

 

Overall, the researchers proved that [⁸⁹Zr]Zr-2-onartuzumab provides specific tumour targeting and high tumour-to-organ contrast on the PET pictures and from the biodisitribution analysis. The results obtained in the study confirm that heptadentate complexes of ⁸⁹Zr display improved stability in vivo compared with hexadentate analogs and are promising candidates for future ⁸⁹Zr-radiotracer design.

About the corresponding author

Jason P. Holland is from Yorkshire in the UK and is currently an SNSF Professor for Medicinal Radiochemistry at the University of Zurich. Research activities in the Holland group focus on advancing radiolabelling methods through novel bioconjugation approaches for labelling bioactive molecules with various radionuclides (¹⁸F, ⁶⁴Cu, ^67/68Ga, ^86/90Y, ^99mTc, ¹¹¹In, ¹⁷⁷Lu, ¹⁸⁸Re, etc).

E-mail: jason.holland@chem.uzh; Twitter: @HollandLab_