Evamarie Hey-Hawkins

University of Leipzig · Institute of Inorganic Chemistry

Invited for this month's cover is the group of Evamarie Hey-Hawkins at Leipzig University. The cover picture shows the three different bonding modes (mono-, bi- and tridentate) of the modular ligand towards palladium(II) or platinum(II), illustrated with Winston who kindly served as the model. The cat has three binding sites (mouth, front paws and...

Sulfur-protected enantiopure P-chiral 1-phosphanorbornane silyl ethers 5a,b are obtained in high yields via the reaction of the hydroxy group of P-chiral 1-phosphanorbornane alcohol 4 with tert-butyldimethylsilyl chloride (TBDMSCl) and triphenylsilyl chloride (TPSCl). The corresponding optically pure silyl ethers 5a,b are purified via crystallizati...

Reversible hydrogen storage in the form of stable and mostly harmless chemical substances such as formic acid (FA) is a cornerstone of a fossil fuels-free economy. In the past, we have reported a primary amine-functionalized bifunctional iridium(III)-PC(sp3)P pincer complex as a mild and chemoselective catalyst for the additive-free decomposition o...

The presence of a large number of boron atoms in boron clusters make them attractive tools for the treatment of cancer using boron neutron capture therapy (BNCT). Since the quantity of boron atoms present in the target cell directly affects the effectiveness of BNCT, the idea of gathering a high number of boron atoms in a single entity has emerged...

The reaction of cyclopentaphosphine cyclo-(P5Ph5) (1) with ketones (acetone and cyclooctanone) in the presence of [Mo(CO)4(cod)] (cod = cycloocta-1,5-diene) led to the air-stable trinuclear complexes in which the bis-phosphanido ligands (PPhPPh-PPh-PPh-CMe2O-PPh)2- (complex 2) and (PPh-PPh-PPh-PPh-C(CH2)7O-PPh)2- (complex 3) bridge a Mo(CO)3-Mo(CO)...

A series of group 6 heterobimetallic complexes [M0;IrIII] (M = Cr, Mo, W) were synthesized and fully characterized, and the catalytic behavior was studied. The heterobimetallic complex [Mo0;IrIII] (C1) was by far the most active and has shown a considerable synergistic effect, with both metals actively participating in homogeneous carbon dioxide hy...

Invited for the cover of this issue is the group of Prof. Evamarie Hey-Hawkins at Leipzig University. The image depicts a deer with diastereomeric antlers. Read the full text of the article at 10.1002/chem.202300790.

In the original publication [...]

Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising...

Oxaliplatin is a third‐generation platinum(II)‐based drug mainly utilized to treat colon cancer, as part of a combinatory regime. Aiming to expand the knowledge on the effects of oxaliplatin and its derivatives on different tumor types, oxaliplatin‐based platinum(IV) platforms are designed and prepared to assess their antitumor capacity against var...

Inspired by multimetallic assemblies and their role in enzyme catalysis, chemists have developed a plethora of heterobimetallic complexes for application in homogeneous catalysis. Starting with small heterobimetallic complexes with σ-donating and π-accepting ligands, such as N-heterocyclic carbene and carbonyl ligands, more and more complex systems...

The reactive P-N bond in a racemic mixture of endo-1-phospha-2-azanorbornene (PAN) (RP/SP)-endo-1 is readily cleaved with enantiomerically pure lithium alkoxides followed by protonation to afford diastereomeric mixtures of P-chiral 1-alkoxy-2,3-dihydrophosphole derivatives. The isolation of these compounds is rather challenging due to the reversibi...

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most widely used therapeutics against pain, fever, and inflammation; additionally, antitumor properties are reported. NSAIDs reduce the synthesis of prostaglandins by inhibiting the cyclooxygenase (COX) isoforms COX‐1 and COX‐2. As nonselective inhibition is associated with off‐target effects, s...

The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer-related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically...

Phosphino hydrazones represent a versatile class of nitrogen-containing phosphine ligands. Herein, we report a modular synthesis of phosphino hydrazone ligands by hydrazone condensation reaction of three different aryl hydrazines with 3-(diphenylphosphino)propanal (PCHO). Complexation reactions of these phosphino hydrazone ligands with palladium(II...

Boron neutron capture therapy (BNCT) is a cancer therapy in which boron delivery agents play a crucial role. In theory, delivery agents with high tumor targeting capabilities can lead to selective eradication of tumor cells without causing harmful side effects. We have been working on a GLUT1-targeting strategy to BNCT for a number of years and fou...

Transition metal coordination chemistry and catalysis are rife with phosphine ligands. One of the rather less studied members of the phosphine ligand family are phosphine aldehydes. We have synthesised 3-(diphenylphosphino)propanal (PCHO) with a slight modification of the known procedure and studied its complexation behaviour with palladium(II) and...

In this communication, we report on the successful application of a high-valent RuIV bifunctional catalyst (1) for mild hydrogenation of cyclic and acyclic carbonates. Our experimental and theoretical studies suggest that the hydrogenation mechanism is operated by an unusual formally zwitterionic RuIV complex. According to our hypothesis, the posit...

The role of ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) in anti-cancer therapy is often challenging, frequently leading to inefficiency of treatments. Cancer cells exploit efflux transporters, like the breast cancer resistance protein (BCRP, ABCG2), to secrete chemotherapeutic substances. In this study, an N-phenyl-2-...

Organotin(IV) carboxylates are a class of compounds explored as alternatives to platinum-containing chemotherapeutics due to propitious in vitro and in vivo results, and distinct mechanisms of action. In this study, triphenyltin(IV) derivatives of non-steroidal anti-inflammatory drugs (indomethacin (HIND) and flurbiprofen (HFBP)) are synthesized an...

The development of cannabinoid receptor type 2 (CB2R) radioligands for positron emission tomography (PET) imaging was intensively explored. To overcome the low metabolic stability and simultaneously increase the binding affinity of known CB2R radioligands, a carborane moiety was used as a bioisostere. Here we report the synthesis and characterizati...

Two heterobimetallic Mo,M’ complexes (M’ = IrIII, RhIII) were synthesized and fully characterized. Their catalytic activity in homogeneous carbon dioxide hydrogenation to formate was studied. A pronounced synergistic effect between the two metals was found, most notably between Mo and Ir, leading to a fourfold increase in activity compared with a b...

The Front Cover shows fish representing fenoprofen analogues. In contrast to the phenyl analogue (left pufferfish), the carborane derivative (right inflated carboranefish) is more cytotoxic. Fenoprofen is a widely used nonsteroidal anti‐inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis, and g...

The encapsulation of icosahedral closo-dicarbadodecaborane (o-, m-, and p-carboranes, Cb) as guest molecules at the intrinsic cavities of the three isostructural tetrahedral cages [{Pd3(NiPr)3PO}4(Cl-AN)6] (1), [{Pd3(NiPr)3PO}4(Br-AN)6] (2), and [{Pd3(NiPr)3PO}4(H-AN)6] (3) was studied. The formation of definite host-guest assemblies was probed wit...

The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tam...

In this work, we present a powerful synthetic strategy for selectively converting phosphole oxides by reaction with sulfonyl isocyanates into the corresponding sulfonylimino phospholes, which show a decrease or increase in solid-state emission.

The ineffectiveness and failing of chemotherapeutic treatments are often associated with multidrug resistance (MDR). MDR is primarily linked to the overexpression of ATP-binding cassette (ABC) transporter proteins in cancer cells. ABCG2 (ATP-binding cassette subfamily G member 2, also known as the breast cancer resistance protein (BCRP)) mediates M...

For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative approaches, leading to hybrid metallodrugs that...

Fenoprofen is a widely used nonsteroidal anti‐inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX‐1 the “house‐keeping” enzyme and COX‐2 the induced isoform from...

The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. We, therefore, focus on the incorporation of metabolically stable, sterically demanding and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhib...

The syntheses of the first B9‐connected carboranylphosphines (B9‐Phos) featuring two carboranyl moieties as well as access to B9‐Phos ligands with bulky electron‐donating substituents, previously deemed unattainable, is reported. The electrochemical properties of the B9‐Phos ligands were investigated, revealing the ability of the mesityl derivative...

The syntheses of the first B9‐connected carboranylphosphines (B9‐Phos) featuring two carboranyl moieties as well as access to B9‐Phos ligands with bulky electron‐donating substituents, previously deemed unattainable, is reported. The electrochemical properties of the B9‐Phos ligands were investigated, revealing the ability of the mesityl derivative...

This proceeding article compiles current research on the development of boron delivery drugs for boron neutron capture therapy that was presented and discussed at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy that took place on April 20-22, 2022. The most used boron sources are icosahedral boron clusters attached to peptid...

Automated X-ray data recording and data reduction strategies are straightforward and powerful these days, as well as semi-automated routines to solve standard structures without, or at least with only little manual intervention and within a relatively short time. The structure determination of the amino-carborane closo -9-[4-(dibenzylamino)phenyl]-...

The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tem...

A synthetic method for a primary 2-(thiophen-2'-yl)ethylphosphine was developed. The reaction of thiophenylethylphosphine with paraformaldehyde and primary arylamines leads to the formation of cyclic bisphosphines, namely, 1,5-di(aryl)-3,7-bis(thiophenylethyl)-1,5-diaza-3,7-diphosphacyclooctane (aryl = phenyl, p-tolyl). The obtained bisphosphines f...

Glucose- and sodium-dependent glucose transporters (GLUTs and SGLTs) play vital roles in human biology. Of the 14 GLUTs and 12 SGLTs, the GLUT1 transporter has gained the most widespread recognition because GLUT1 is overexpressed in several cancers and is a clinically valid therapeutic target. We have been pursuing a GLUT1-targeting approach in bor...

Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites such as inflammatory mediators—prostaglandins and leukotrienes. The inhibition of lipoxygenases is increasingly employed in the treatment of cancer. We evaluated the anticancer potential of two novel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, whi...

Hepta-tert-butylnonaphosphane {cyclo-(P4tBu3)}2PtBu was employed as a ligand in transition metal complexes of iron(0) (1), cobalt(-I) (2), copper(I) (3) and rhodium(I) (4), which are readily formed in moderate to good yields, and an unstable palladium(II) complex (5). The ligand features three different bonding modes (one monodentate (compounds 1 a...

Mefenamic acid represents a widely used nonsteroidal anti-inflammatory drug (NSAID) to treat the pain of postoperative surgery and heavy menstrual bleeding. Like other NSAIDs, mefenamic acid inhibits the synthesis of prostaglandins by nonselectively blocking cyclooxygenase (COX) isoforms COX-1 and COX-2. For the improved selectivity of the drug and...

High‐valent metal complexes are viable candidates for hydrogenation catalysts: The domain of catalytic hydrogenation is traditionally dominated by low‐valent metals; however, the heterolytic bond‐splitting mechanism does not require an electron‐rich metal. Here we report a structurally well‐defined ruthenium(IV) catalyst capable of hydrogen activat...

The reaction of heteroditopic ligand 1 featuring a hard pyridine-hydrazone-pyrimidine (N,N,N) site and a softer pyrimidine-hydrazone-phosphane (N,N,P) pocket with [Pd(CH3CN4)](OTf)2 in different metal-to-ligand ratios (M:L) gave the homobimetallic PdII complex [Pd2(1)(CH3CN)2](OTf)4 (2, M:L ratio 2:1), the [4+4] metallomacrocyclic PdII complex [Pd(...

A frustrated Lewis pair reminds us of a dog trying to lick a tail wound but being unable to do so because the bulky protective collar prevents this. Note the cute carborane‐shaped dog toy to relieve frustration until the wound is fully healed. More information can be found in the Research Article by E. Hey‐Hawkins and co‐workers (DOI: 10.1002/chem....

The synthesis of phosphorus-rich analogues of carbon-based compounds is a desirable but challenging endeavour. Now, the synthesis of the anion [Fe(P4)2]2– is reported, which so far is the most similar all-phosphorus relative to well-known ferrocene, [Fe(η5-C5H5)2].

Low‐valent metals traditionally dominate the domain of catalytic hydrogenation. However, metal‐ligand cooperating (MLC) catalytic systems, operating via heterolytic H‐H bond splitting by a Lewis acidic metal and a basic ligand site, do not require an electron‐rich metal. On the contrary, high‐valent metals that induce weaker back donation facilitat...

The conversion of biomass into sustainable biofuel is achievable through biorefinery. In this regard, the selective hydrogenation of furfural to furfuryl alcohol, 2-methylfuran, and tetrahydrofurfuryl alcohol has attracted a great interest. This research aims to prepare an active and selective catalyst for hydrogenation of furfural in liquid phase....

The primary phosphines MesPH 2 and t ‐BuPH 2 react with 9‐iodo‐ m ‐carborane yielding B9‐connected secondary carboranylphosphines 1,7‐H 2 C 2 B 10 H 9 ‐9‐PHR, R = 2,4,6‐Me 3 C 6 H 2 (Mes) ( 1a ), t‐ Bu ( 1b )). Addition of tris(pentafluorophenyl)borane (BCF) to 1a,b resulted in the zwitterionic compounds 1,7‐H 2 C 2 B 10 H 9 ‐9‐PHR( p ‐C 6 F 4 )BF(...

The reaction of tetra-tert-butylcyclotetraphosphane cyclo-(PtBu)4 (L) with one to four equivalents [AuCl(tht)] (tht = tetrahydrothiophene) leads to the gold(I) complexes [(AuCl)nL] (n = 1–4, 1–4) in which the ligand coordinates...

Correction for ‘Facile synthesis of cyclo -(P 4 t Bu 3 )-containing oligo- and pnictaphosphanes’ by Volker Jens Eilrich et al. , Dalton Trans. , 2021, 50 , 14144–14155, DOI: 10.1039/D1DT02639A.

The treatment of Parkinson's disease (PD) has not been consistently modified for more than 60 years. L-DOPA, the blood–brain barrier permeable precursor prodrug of dopamine, is to date the only effective therapy on the market. However, it is well known that prolonged treatment with L-DOPA leads to several side effects, which may affect the patient'...

The title compound [Au2{μ-(SC6H4-2-AsPh2)-κS,κAs}2] consists of a dinuclear unit with two AsS– ligands (AsSH = 1-AsPh2-2-SHC6H4) bridging the gold(I) atoms. Each gold(I) atom is coordinated by a sulfur atom from one ligand and one arsenic atom from the other ligand with formation of a ten-membered centrosymmetric Au2As2S2C4 ring. The deviation of t...

Aryl-substituted sodium 3,4,5-triaryl-1,2-diphosphacyclopentadienides Na(C3R3P2) (R = Ph, 4-Me-C6H4, 4-Cl-C6H4, 1a-c) react with [FeCp(η6-C6H5CH3)][PF6] to give heteroleptic 3,4,5-triaryl-1,2-diphosphaferrocenes [FeCp(η5-P2C3R3)] (2a-c) in 71-78% yield. The structures of 2a-c were confirmed by NMR,...

For the development of anticancer drugs with higher activity and reduced toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II) counterparts and loading them into mesoporous silica SBA-15 with the aim to utilise the passive enhanced permeability and retention (EPR) ef...

The zeolitic imidazolate framework ZIF-8 (Zn(mim)2, mim = 2-methylimidazolate) has recently been proposed as a drug delivery platform for anticancer therapy based on its capability of decomposing in acidic media. The concept presumes a targeted release of encapsulated drug molecules in the vicinity of tumor tissues that typically produce secretions...

12‐Lipoxygenase is crucial for tumour angiogenesis. 5,6,7‐Trihydroxy‐2‐phenyl‐4 H ‐1‐benzopyran‐4‐one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo . Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carb...

Direct conversion of elemental white phosphorus (P4) to organophosphorus compounds is an attractive and challenging goal in sustainable phosphorus chemistry. We report here the one-pot reaction of P4, sodium metal and (1,2,3-triphenylcyclopropenyl)phosphonium bromides 1a,b to give exclusively sodium 3,4,5-triphenyl-1,2-diphospholide 2. An electroch...

The cyclo-(P4tBu3) synthon [Li{cyclo-(P4tBu3)}(thf)(tmeda)] (1) (thf = tetrahydrofuran, tmeda = N,N,N',N'-tetramethylethane-1,2-diamine) is readily accessible in a one-pot synthesis from P4 and LitBu. The use of 1 as a cyclo-(P4tBu3) building block enables the rational synthesis of cyclo-(P4tBu3)-containing oligophosphanes, namely {cyclo-(P4tBu3)}2...

A straightforward synthesis of the tetradentate phospholane ligand 1 is reported. The 2 : 1 [M : L] reaction of 1 with [AuCl(tht)] (tht = tetrahydrothiophene) resulted in the 4 : 2 [M : L] supramolecular coordination complex 2 where two ligands 1 are bridging four gold(I) cations. The formation of 2 can be rationalised via a geometrical analysis of...

The elevated expression of histone deacetylases (HDACs) in various tumor types renders their inhibition an attractive strategy for epigenetic therapeutics. One key issue in the development of improved HDAC inhibitors (HDACis) is the selectivity for single HDAC isoforms over unspecific pan inhibition to minimize off-target toxicity. Utilizing the ca...

Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-inva...

Oxidative addition of the P-P single bond of an ortho-carborane-derived 1,2-diphosphetane (1,2-C2(PMes)2B10H10) (Mes = 2,4,6-Me3C6H2) to cobalt(-i) and nickel(0) sources affords the first heteroleptic complexes of a carborane-bridged bis(phosphanido) ligand. The complexes also incorporate labile ligands suitable for further functionalisation. Thus,...

The Cover Feature shows the integration of various elaborate physical and chemical methods to prepare cobalt nanoparticles (CoNPs), which can be obtained in different forms depending on the used method. The application of modern analytical methods like TEM, SEM, XRD, EPR, etc. for determining the size, shape, and properties of the generated CoNPs i...

Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the development of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective autophagy. In this work, we investigated the role and mechanism of action of the combination of a ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked...

In this review, the scientific progress of the last 30 years on the chemistry, synthetic procedures and the reactivity of cyclooligophosphanes is presented. Cyclooligophosphanes display a rich coordination chemistry which is still only barely explored. ³¹P NMR spectroscopy is a powerful tool for the characterisation of phosphorus-rich compounds. Fu...

The development of modern chemistry is currently proceeding in several priority areas including investigations focused on the synthesis, stabilisation and application of transition metal nanoparticles (NPs), which are widely used in physical, chemical, engineering and biomedical processes. A special place among known transition metal NPs is occupie...