Inorganic Chemistry Frontiers Blog

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_

We are delighted to announce the Best Inorganic Chemistry Frontiers Covers of 2021!

Read below the scientific papers.

A red-light-chargeable near infrared MgGeO₃:Mn²⁺,Yb³⁺ persistent phosphor for bioimaging and optical information storage applications

Binuclear metal complexes with a novel hexadentate imidazole derivative for the cleavage of phosphate diesters and biomolecules: distinguishable mechanisms

The efficient semihydrogenation of internal alkynes to selectively produce either E– or Z-alkenes is one of the main challenges in homogeneous catalysis. Numerous systems were reported in the past, however, such reactions typically require either the use of gaseous hydrogen at high pressure, noble metal catalysts, or rather high catalyst loading at long reaction times, the latter resulting in alkene isomerisation or overreduction to produce alkanes. Amine boranes such as ammonia borane (H₃B·NH₃) are known to be well-suited for transfer hydrogenation reactions, providing stoichiometric amounts of H₂ either by dehydrogenation (i.e. H₂ production), followed by hydrogenation, or by stepwise hydride and proton transfer to an organic substrate. Homogeneous precatalysts based on the Co(II) oxidation state have been reported in the past, however, mechanistic insights into such systems were rather limited to date.

Recently, the groups of Jiao and Beweries at LIKAT Rostock have demonstrated that PNN(H) Co(II) complexes serve as very efficient precatalysts for the selective formation of E-alkenes at very mild conditions, suing MeOH and H₃B·NH₃ as the hydrogen source. This reaction is suggested to take place exclusively via the Co(II) oxidation state, which was corroborated though a combination of control experiments, EPR spectroscopy, and DFT analysis. Key feature for the high activity of this Co system is the proton responsive PNN(H) ligand, possessing a pyrazole fragment that undergoes deprotonation during catalyst activation. The results presented herein could be relevant for the design of other proton responsive ligands for non-noble metal free transfer hydrogenation reactions.

Corresponding author:

PD Dr. Torsten Beweries (Leibniz Institute for Catalysis, Rostock)

Torsten Beweries is head of the department Coordination Chemistry and Catalysis at the Leibniz Institute for Catalysis in Rostock (Germany). He received his PhD in Chemistry at LIKAT in 2008, working on the coordination chemistry of hafnocenes. He then moved to the University of York (UK) for a postdoctoral stay with Prof. Robin N. Perutz in 2009, working on late transition metal complexes for halogen bonding. He returned to LIKAT in 2010, where he established an independent research group. The research field of PD Dr. Torsten Beweries is organometallic chemistry and homogeneous catalysis with focus on new pincer ligands and complexes, main group polymers, and unusual metalacyclic systems. He is the author of 91 articles indexed by SCI and cited more than 1600 times with an index H = 23.

Organometallic chemistry of the rare earth and actinide elements has been a driving force for the development of novel functional materials and catalysts for decades, giving rise to impressive advances in the fields of single-molecule magnetism, luminescence, and polymer sciences. Excitingly, organometallic approaches have always been on the forefront of fundamental chemistry and allowed breakthroughs in the field, not only with the lighter metals but also some of the heaviest actinide candidates. The inherent reactivity of organometallic compounds owing to the apparent labile and reactive metal-carbon bonds renders the isolation and characterization of such molecules exceptionally challenging, especially when aiming at polymetallic rare earth complexes, and is therefore underdeveloped to this date. Consequently, the exploration of suitable synthetic routes to access bridged organometallic metallocene complexes is of great interest for the rare earth and more general inorganic chemistry community.  

Recently, the group of Selvan Demir at Michigan State University has demonstrated that two rare earth metallocene fragments are able to capture the tetradentate salophen ligand, giving rise to the first series of dinuclear salophen-bridged rare earth metallocene complexes with the metals yttrium, gadolinium and dysprosium, Figure 1. These molecules also constitute the first metallocene salophen complexes for any metal ion. Remarkably, the flexibility of the salophen bridge allows the binding pockets to face outwards upon complexation to the metal ions which is a rare, yet intriguing, coordination mode. Consequently, a substantial separation of the metal centers (7.858 – 7.895 Å) occurs leading to weak electronic or magnetic communication between the rare earths. Since the magnitude of magnetic exchange coupling between paramagnetic metal centers and/or organic radical is crucial for the generation of better-performing multinuclear single-molecule magnets,  the magnetic communication in these salophen complexes was explored. 

The dynamic magnetic properties of the paramagnetic dysprosium complex revealed characteristics of single-molecule magnet behavior, while the static magnetic susceptibility data collected for the paramagnetic gadolinium complex allowed quantification of the magnetic exchange, Figure 2. The determined coupling is of similar magnitude to other polynuclear rare earth complexes containing diamagnetic bridging ligands. DFT calculations on the diamagnetic yttrium conger revealed negligible orbital overlap between the metal center and the salophen ligand in the highest occupied molecular orbital, Figure 1, which may account for the weak magnetic coupling in the paramagnetic variants.

Notably, the lowest unoccupied molecular orbital might be able to be populated with an unpaired electron. Radicals, innate to unpaired electrons, promote strong exchange coupling when placed between rare earth magnetic moments and are, thus, extremely sought-after in the fields of single-molecule magnetism and spintronics. Excitingly, cyclic voltammetry measurements of the salophen

complexes revealed a quasi-reversible feature attributed to the reduction and oxidation of the salophen bridge on the timescale of the electrochemical experiment, Figure 2. This paves the way for chemical reductions of these molecules to generate coveted metal-radical compounds in the future. Noteworthy, chemical functionalization of the salophen backbone may readily be attained which serves as an additional path to augment magnetic coupling and as such highlights the enormous potential of the salophen ligand in organometallic chemistry.

Selvan Demir is an Assistant Professor of Chemistry at Michigan State University. She earned her Dr. rer. Nat. at 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 focused on lanthanide-based single-molecule magnets and porous aromatic frameworks with Prof. Jeffrey R. Long at the University of California, Berkeley, and worked on 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. The research group focuses mainly on organometallic chemistry, small molecule activation, single-molecule magnetism, and lanthanide/actinide separations. A particular emphasis is also on heavy p-block element and uranium chemistry.

 

 

 

Amongst the myriad uses of metal-organic frameworks (MOFs) and coordination polymers, separation of complex mixtures, either gaseous or in solution, is one of the most promising applications due to the regular array of well-defined pores. Integration of specific points of interaction that are complementary to the targeted guest species can provide highly selective materials. In particular, precise control of the 3D space within pores may provide a mechanism for enantioselective discrimination for which the exact spatial arrangement of multiple sites of interaction is paramount.

The vast majority of research in this area is driven by 3D metal-organic frameworks, often those possessing permanent porosity. However, for solution-based applications this need not be a prerequisite and materials comprising lower dimensionality coordination polymers may be just as effective is they contain solvent-filled pores.

Recently the group of David Turner at Monash University has shown that a 1D coordination polymer, with pores formed by alignment of loops within the 1D chain, is capable of sorbing 1-phenylethanol with a good degree of enantioselectivity (Figure 1). A closely related material shows no such selectivity, and a reduced uptake capacity, highlighting the importance of structural match between the host framework and the analyte. Ground samples showed higher uptake than unground crystals for the active material, suggesting an influence of surface area or ease of permeation into the solid. Both static (soaking) and dynamic (“micro-LC”) methods showed enhanced uptake of one enantiomer from a racemic solution of 1-phenylethanol, albeit not perfect separation. The group was also able to crystallographically determine the binding site of the preferred enantiomer (Figure 2), showing an array of hydrogen bonding interactions that lie behind the enhanced uptake of one enantiomer over the other.

These results highlight the potential of non-3D coordination polymers in chemical separations and demonstrate the array of host-guest interactions that are required for separations of very similar compounds.

Corresponding Author:

David Turner is a Senior Lecturer in the School of Chemistry at Monash University, Australia. After receiving his PhD in 2004 from King’s College, London, he held a number of fellowships at Monash University prior to joining as a Faculty member. Research in the Turner group revolves around metallosupramolecular assemblies, exploring both coordination polymers/MOFs and coordination cages with a particular emphasis on chirality. Dr Turner has published over 130 papers, in addition to two books, attracting almost 5000 citations and an h-index of 32.

https://research.monash.edu/en/persons/david-turner

Since Wilson and Flanigen found the first microporous aluminophosphate (AlPO) in 1982, the synthesis of AlPO materials with novel frameworks and study their potential properties, such as adsorption, catalysis, and separation, has attracted intense interest of researchers. As the main family of AlPO based materials, 2D layered materials show a rich variety of structures and compositions depending on the diverse coordination and connection modes of Al and P atoms. In recent years, 2D materials, possessing highly exposed surfaces and diverse structures, have become a dramatic category of supports. However, 2D molecular sieves are serving as catalyst supports are very few.

Recently, Prof. Jiuxing Jiang at Sun Yat-sen University and Dr. Jiang-Zhen Qiu of Zhongkai University of Agriculture and Engineering synthesized a new 2D layered aluminophosphate compound by adopting rigid and bulky template of 3,5,N,N-tetramethyladamantane-1-amine (ada) through hydrothermal conditions, which is named the Zhongkai University of Agriculture and Engineering NO.1 (ZHKU-1), with the composition |Hada|₆[Al₆(PO₄)₈](H₂O)₁₁. The structure of ZHKU-1 was constructed from the alternate connection of AlO₄ and triply bridged PO₄ tetrahedra ([O=PO₃]^3-) to form a 4, 6, 12-net (Figure 1). The inorganic sheets are linked and separated by protonated amine and H₂O molecules by extensive H-bonds, giving a new 2D structure with an interlayer space of 19.6 Å.

ZHKU-1, as a 2D material with a more exposed surface, could be adapted for encapsulating metal nanoparticles (NPs). Ag species are immobilized on the supports of ZHKU-1 by UV reduction and deposition, forming the catalyst of Ag@ZHKU-1 with high loading of 4.9 wt%. The HRTEM images reveal the highly uniform Ag clusters with visually observed sizes of 1.9 nm (Figure 2).

Since 4-nitrophenol (4-NP) is a notorious industrial pollutant, Ag@ZHKU-1 is applied to the model reaction for 4-NP reduction. The catalytic results show that the reduction reaction of 4-NP into 4-aminophenol could be completely performed within 75 s in NaBH₄ solution (Figure 3). Moreover, the catalytic activity was almost the same, with almost 99% conversion after eight cycles. The remarkable catalytic activity and recyclability of Ag@ZHKU-1can be attributed to the high dispensability of Ag nanoclusters confined to the 2D support, which provides more accessible Ag active sites to 4-NP.

This work reports a new 2D layered aluminophosphate compound, which expends the aluminophosphates family. Furthermore, the confinement of metal Ag on this new layer structure through photodeposition gives rise to a small size (~1.9 nm) of AgNPs with homogeneous dispersion. The catalyst of Ag@ZHKU-1 shows excellent catalytic activity and high conversion for 4-nitrophenol reduction. This work is significant for designing 2D aluminophosphate materials to confine small metal nanoparticles for catalytic application.

Prof: Jiuxing Jiang (ORCID: 0000-0001-9664-3235). I received Ph.D degree from Jilin University in 2010. Afterward, I spent 5 years for a Post Doc. stay in Instituto Technologia Quimica (UPV-CSIC) in Valencia Spain supervised by Prof: Avelino Corma. After independent work in Sun Yat-sen University (2015-now), I keep my interesting on the topologically new zeolite synthesis (four three letter code, IRR, -IRY, -IFU, -SYT were granted by Structure Committee of Internation Zeolite Association), and zeolite based heterogeneous catalysis, such as: acid-base catalysis, catalytic ammonium synthesis, NH₃-SCR for deNOx reaction, porous materials for energy storage, etc. I have published more than 20 high-impact journal articles, such as Science, Angew. Chem. Int, Ed, Chem.Sci, Chem. Mater. etc. Among them, the work on the synthesis and structure of zeolite ITQ-43 was published in Science, 2011, 333, 1131-1134 and was selected as annually breakthrough of 2011 by Science. Currently serve as a member of Zeolite Committee of Chinese Chemical Society and youth editorial member of Journal of Chemical Research in Chinese University.

Jiang-Zhen Qiu: She received her Ph.D. degree in 2019 from Sun Yat-sen University with M.S. Supervisor Prof. Ming-Liang Tong and Ph.D. Supervisor Prof. Jiuxing Jiang. In 2020, she was introduced to Chemical Engineering of Zhongkai University of Agriculture and Engineering as an “Excellent Doctor”. Her interested research fields include synthesizing new topological structures of zeolite and exploring multifunctional materials with novel functionalities such as light, conductivity, magnetism, or catalysis. Currently, she and her collaborators published 10 papers in related fields, such as Chem. Mater., Chem. Sci., Inorg. Chem. Front., Chem. Commun., Chem. Eur. J.