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For the first time, the capture of the planar antiaromatic parent benzene dianion in between two trivalent rare earth (RE) metal cations (RE III ), each stabilized by two guanidinate ligands, is reported. The synthesized inverse-sandwich complexes [{(Me 3 Si) 2 NC(N i Pr) 2 } 2 RE] 2 (μ-η 6  : η 6 -C 6 H 6 ), (RE=Y (1), Dy (2), and Er (3)) were crystallized from aprotic solvents and feature a remarkably planar parent benzene dianion, previously not encountered for any metal ion prone to low or absent covalency. The -2 charge localization at the benzene ligand was deduced from the results obtained by single-crystal X-ray diffraction analyses, spectroscopy, magnetometry, and Density Functional Theory (DFT) calculations. In the 1 H NMR spectrum of the diamagnetic Y complex 1, the equivalent proton resonance of the bridging benzene dianion ligand is drastically shifted to higher field in comparison to free benzene. This and the calculated highly positive Nucleus-Independent Chemical Shift (NICS) values are attributed to the antiaromatic character of the benzene dianion ligand. The crucial role of the ancillary guanidinate ligand scaffold in stabilizing the planar benzene dianion conformation was also elucidated by DFT calculations. Remarkably, the planarity of the benzene dianion originates from the stabilization of the π-type orbitals of the d-manifold and compression through its strong electrostatic interaction with the two RE III sites., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Anionic ancillary ligands play a critical role in the construction of rare earth (RE) metal complexes due to the large influence on the stability of the molecule and engendering emergent electronic properties that are of interest in a plethora of applications. Supporting ligands comprising oxygen donor atoms are highly pursued in RE chemistry owing to the high oxophilicity innate to these ions. The scarcely employed bis(acyl)phosphide (BAP) ligands feature oxygen coordination sites and contain a phosphide backbone rendering it attractive for RE-coordination chemistry. Here, we integrate bis(mesitoyl)phosphide ( mes BAP) as an ancillary ligand into RE III chemistry to generate the first dinuclear trivalent RE complexes containing BAP ligands; [{ mes BAP} 2 RE(THF)(μ-Cl)] 2 (RE=Y, (1), Gd (2), and Dy (3); THF=tetrahydrofuran). Each RE center is ligated to two monoanionic mes BAP ligands, one THF molecule and one chloride ion. All three molecules were characterized through single-crystal X-ray diffraction, 31 P NMR, IR and UV-Vis spectroscopy. 31 P, 1 H and 13 C NMR on the diamagnetic yttrium congener 1 confirm asymmetric ligand coordination. DFT calculations conducted on 2 provided insight into the electronic structure. The magnetic properties of 2 and 3 were investigated via SQUID magnetometry. The Gd III ions exhibit weak antiferromagnetic coupling, corroborated by DFT results., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

The seminal isolation of a dinuclear rare earth metal complex comprising a bridging 2,2'-azobispyridyl radical anion, [(Cp tet 2 Y) 2 (μ-abpy˙)](BPh 4 ), is presented, which was obtained from a one-electron chemical oxidation of [(Cp tet 2 Y) 2 (μ-abpy)]. The unprecedented compounds were characterized by crystallography, spectroscopy and DFT computations. The radical character was proven by EPR spectroscopy.

The generation of noncovalent intermolecular interactions represents a powerful method to control molecular vibrations and rotations. Combining these with the axial ligand field enforced by the metallocene ligand scaffold provides a dual-pronged approach in controlling the magnetic-relaxation pathways for dysprosium-based single-molecule magnets (SMMs). Here, we present the first implementation of 2,3,4,5-tetraiodopyrrole (TIPH) in its anionic form [TIP] - as a ligand in three isostructural rare-earth metal complexes Cp* 2 RE(TIP) (1-RE, RE = Y, Gd, and Dy; Cp* = pentamethylcylopentadienyl), where the TIP ligand binds through the nitrogen and one iodine atom κ 2 (N,I) to the metal centre. The shallow potential energy surface of the intermolecular σ-hole interaction yields distortions of the interatomic distances at elevated temperatures which were investigated by variable-temperature SCXRD. 1-RE constitute the first crystallographically characterized molecules containing TIP as a ligand for any metal ion, and 1-Dy is the first SMM that employs the TIP ligand. The structural dependence on temperature allowed the mechanism of magnetic relaxation to be explored through ab initio calculations at different temperatures. The electronic influence of the coordinated iodine substituent was probed via magnetometry and cw-EPR spectroscopy on 1-Gd. To further scrutinize the impact of the iodine substituents on the physical properties, a second set of new complexes Cp* 2 RE(DMP) (2-RE, RE = Y, and Dy) where DMP = 2,5-dimethylpyrrolyl were synthesized. Here, the DMP ligand binds similarly to the TIP ligand and represents an all-hydrocarbon analogue to 1-RE. 2-Dy constitutes the first SMM bearing a DMP ligand., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ancillary ligand scaffolds that sufficiently stabilize a metal ion to allow its coordination to an open-shell ligand are scarce, yet their development is essential for next-generation spin-based materials with topical applications in quantum information science. To this end, a synthetic challenge must be met: devising molecules that enable the binding of a redox-active ligand through facile displacement and clean removal of a weakly coordinating anion. Here, we probe the accessibility of unprecedented radical-containing rare-earth guanidinate complexes by combining our recently discovered yttrium tetraphenylborate complex [{(Me 3 Si) 2 NC(N i Pr) 2 } 2 Y][(μ-η 6 -Ph)(BPh 3 )] with the redox-active ligands 2,2'-bipyridine (bpy) and 2,2'-bis(benzimidazole) (Bbim), respectively, under reductive conditions. Our endeavor resulted in the first evidence of guanidinate complexes that contain radicals, namely, a mononuclear bipyridyl radical complex, {(Me 3 Si) 2 NC(N i Pr) 2 } 2 Y(bpy • ) ( 1 ), and a dinuclear bis(benzimidazolyl) radical-bridged complex, [K(crypt-222)][{(Me 3 Si) 2 NC(N i Pr) 2 } 2 Y] 2 (μ-Bbim • ) ( 2' ). The latter was achieved by an in situ reduction of [{(Me 3 Si) 2 NC(N i Pr) 2 } 2 Y] 2 (μ-Bbim) ( 2 ), which was isolated from a salt metathesis reaction. 1 and 2 were characterized by X-ray crystallography and IR and UV-vis spectroscopy. Variable-temperature electron paramagnetic resonance spectroscopy was applied to gain insight into the distribution of unpaired spin density on 1 and 2' . Density functional theory calculations were conducted on 1 and 2' to elucidate further their electronic structures. The redox activity of 1 and 2' was also probed by electrochemical methods.

The π- and σ-basicity of the pyrrolyl ligand affords several coordination modes. A sterically encumbering coordination sphere around metal centers may foster new coordination modes for the pyrrolyl ligand. Here, we present three dinuclear rare earth complexes [Cp* 2 RE(μ-pyr)] 2 , [RE = Y ( 1 ), La ( 2 ), Dy ( 3 ); Cp* = pentamethylcyclopentadienyl, pyr = pyrrolyl], which were synthesized through a protonolysis reaction between allyl complexes and H-pyrrole. Each metal is ligated by two Cp* ligands and the N atom of the pyrrolyl ring while interacting with the π-system of the other pyrrolyl ligand, yielding an unprecedented coordination mode for pyrrolyl best described as [((η 5 -Cp*) 2 RE) 2 (μ-1η 2 -pyr-2κN)(μ-2η 2 -pyr-1κN)]. The steric congestion implemented by the Cp* ligands forces this asymmetric coordination of the pyrrolyl ligand. 1 - 3 were characterized by crystallography, electrochemistry, and spectroscopy. Density functional theory calculations on 1 uncovered the bonding situation between the pyrrolyl ligand and the yttrium(III) ion. Excitingly, 3 displays slow magnetic relaxation under zero dc field with U eff = 98.9(7) cm -1 and τ o = 6.7(1) × 10 -8 s, placing it among coveted dinuclear metallocene single-molecule magnets. CASSCF calculations provided the energy of the crystal field states of Dy III and confirmed the barrier height.

A room temperature stable complex formulated as Y(NHAr*) 2 has been prepared, where Ar* = 2,6-(2,4,6-( i Pr) 3 C 6 H 2 )C 6 H 3 , by KC 8 reduction of ClY(NHAr*) 2 . Based on EPR evidence, Y(NHAr*) 2 is an example of a d 1 Y(ii) complex with significant delocalization of the unpaired electron density from the metal to the ligand. The isolation of molecular divalent metal complexes is challenging for rare earth elements such as yttrium. In fact, stabilization of the divalent state requires judicious ligand design that allows the metal center to be coordinatively saturated. Divalent rare earth elements tend to be reactive towards various substrates. Interestingly, Y(NHAr*) 2 reacts as a radical donor towards t BuNC to generate an unusual yttrium isocyanide complex, CNY(NHAr*) 2 , based on spectroscopic evidence and single-crystal X-ray diffraction data., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Isolable heteroleptic tris(metallocenes) containing five-membered and larger rings remain extremely scarce. The utilization of tripositive rare-earth-metal ions with ionic radii >1 Å allowed access to unprecedented and sterically congested dibenzocyclooctatetraenyl (dbCOT) metallocenes, [K(crypt-222)][Cp tet 2 RE(η 2 -dbCOT)] (RE = Y ( 1 ), Dy ( 2 ); Cp tet = tetramethylcyclopentadienyl), through a salt metathesis reaction involving Cp tet 2 anion in a complex containing d- or f-block metals. Remarkably, the (Cp 4 ) and the potassium salt of the dbCOT dianion. The solid-state structures were investigated by single-crystal X-ray diffraction, magnetometry, and IR spectroscopy and provided evidence for the first crystallographically characterized (dbCOT) 2- anion in a complex containing d- or f-block metals. Remarkably, the (Cp tet ) - ligands force a distortion from planarity within the (dbCOT) 2- moiety, engendering a rare η 2 -bonding motif, as opposed to the classical η 8 conformation observed in complexes bearing a (COT) 2- ion. The η 2 coordination mode was proven crystallographically between 100 and 298 K and computationally (DFT and NBO). Furthermore, nucleus independent chemical shift (NICS) calculations uncovered significant ring current within the dbCOT ligand. The solution-state properties of 1 and 2 were analyzed via cyclic voltammetry, NMR, and UV-vis spectroscopy. Cyclic voltammograms of 1 and 2 exhibit a quasi-reversible feature indicating the accessibility of complexes with dbCOT in two oxidation states (dbCOT 2-/3-• ). Importantly, the dysprosium congener, 2 , is a zero-field single-molecule magnet (SMM).

Background: Prompt diagnosis and treatment of acute mesenteric ischemia (AMI) requires a high index of suspicion for timely management. Poor clinical outcomes and delays in surgical treatment are demonstrated even in modern clinical series. Recognition of exhaled volatile organic compounds (VOCs) specific to AMI may facilitate early detection and diagnosis and improve patient outcomes., Methods: Adult Wistar rats (n = 5) were intubated and anesthetized, and control tracheostomy breath samples were collected using Tedlar gas sample bags. Intestinal ischemia was induced by placing an occlusive clip across the superior mesenteric artery, and breath samples were collected after 1 hour of intestinal ischemia and after 15 minutes of intestinal reperfusion. Gas chromatography was used to identify and measure levels of VOCs obtained, and measured retention indices were compared with known values in the Kovats retention index database., Results: Multiple retention indices (n = 41) were noted on gas chromatography, representing a variety of VOCs detected. Z,Z-farnesol (C15H26O), an isoprenoid, was the only compound detected that was undetectable during the control phase (median = 0 cts/sec) but which significantly elevated during the ischemic (median = 34 cts/sec, range = 25-37) and reperfusion (median = 148 cts/sec, range = 42-246) phases. Three other isoprenoid compounds (E,E-alpha-farnesene, germacrene A, and Z,Z-4,6,8-megastigmatriene) were also detected in all five animals, but their levels did not differ significantly between control, ischemic, and reperfusion phases., Conclusions: This pilot study demonstrates the feasibility of analyzing exhaled VOCs using a novel rat model for AMI. These findings may be useful for the development and identification of similar assays for the rapid diagnosis of AMI., (Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

One of the key features of cardiovascular complications, such as hypertension or diabetes, is that they often appear at the same time in the same individual together with other forms of co-morbidities. While clinically a recognized phenomenon, no molecular mechanism for such co-morbidities has received universal acceptance. We propose a new hypothesis that provides a molecular basis for co-morbidities in hypertension due to unchecked proteolytic activity and receptor destruction. Testing of the hypothesis in the spontaneously hypertensive rat reveals an unchecked matrix metalloproteinase and serine protease activity in plasma and on several cardiovascular and parenchymal cells. The elevated proteolytic activity causes extracellular cleavage of multiple receptor types, such that cleavage of one receptor type leads to loss of the function carried out by this receptor. Proteolytic cleavage of the extracellular domain of the β(2) adrenergic receptor in arteries and arterioles causes vasoconstriction and elevation of the central blood pressure while cleavage of the extracellular domain of the insulin receptor leads to insulin resistance and lack of transmembrane glucose transport. A diverse set of cell dysfunctions in the spontaneously hypertensive rat are accompanied by cleavage of the membrane receptors that are involved in these functions. Chronic inhibition of the unchecked protease activity in the spontaneously hypertensive rat serves to restore the extracellular receptor density and alleviates the corresponding cell dysfunctions. The mild unchecked proteolytic activity in the spontaneously hypertensive rat points towards a chronic autodigestion process as a contributor to the end organ injury encountered in this rat strain. The presence of various soluble receptors, which consist of extracellular fragments of membrane receptors, in the plasma of hypertensive and diabetic patients suggest that the autodigestion process may also be present in man.

Objective: In vitro studies suggest that microhemorrhages with escape of red cells into the tissue may be cytotoxic to parenchymal cells due to oxygen free radical formation. We examined in the rat mesentery the impact of microhemorrhages on parenchymal cell death, as detected by propidium iodide staining, using an intravital approach., Methods and Results: Postcapillary venules were punctured with a closed-end micropipette, permitting escape of blood cells and plasma into the mesentery interstitium. Over a period of 2 h, no significant increase in parenchymal cell death was encountered in tissues with hemorrhagic sites compared with nonhemorrhagic control sites. Interstitial microinjections of plasma derived from whole blood incubated for several hours with and without a combination of sodium azide (2 mM) and hydrogen peroxide (1 mM) led to significantly increased levels of cell death compared to control experiments. Interventions against the hydroxyl radical with dimethylthiourea (DMTU, 2 mM) or 2,2'-dipyridyl (DPD, 2 mM), a lipid soluble iron chelator, provided no protective effect against the parenchymal cell death. DMTU slightly delayed tile cytotoxic reaction., Conclusions: These observations suggest that a newly formed microhemorrhage is not necessarily cytotoxic to parenchymal tissue cells. Interstitial microinjections of plasma, derived from whole blood after prolonged exposure to oxygen free radicals or just aging under in vitro conditions, may be cytotoxic to mesenteric parenchymal cells without effective blockade by interventions against the hydroxyl radical.

Objective: To determine if oxygen free radicals derived from xanthine oxidase are involved in the development of salt-induced hypertension. Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction and provide a mechanism for lesion formation., Methods: Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed either a low-salt, high-salt or high-salt + tungsten diet for 4 wk. In vivo production of superoxide (O2-) was detected by the reduction of a tetranitroblue tetrazolium (TNBT) dye in the rat mesentery, while plasma hydrogen peroxide (H2O2) production levels were determined using a modified electrochemical electrode technique., Results: The tungsten diet lowered the blood pressure of Dahl-S rats compared to high-salt-treated Dahl-S rats, but had no effect on blood pressure in Dahl-R rats. Light absorption of formazan deposits revealed that tungsten-treated Dahl-S rats had reduced TNBT staining along the endothelium of arterioles and venules compared to hypertensive, high-salt-treated Dahl-S rats. In addition, tungsten-treated Dahl-S rats had a lower plasma H2O2 concentration compared to hypertensive, high-salt-treated Dahl-S rats., Conclusions: These findings indicate that xanthine oxidase-derived oxygen free radicals are involved in the pathogenesis of salt-induced hypertension.

Objective: The objective of this study was to explore the degree of parenchymal cell injury after mast cell degranulation by application of compound 48/80 (CMP 48/80) in the absence of adherent leukocytes in the rat mesentery., Methods: Rats were rendered leukopenic by injection of an antibody against leukocytes, and the mesentery was superfused with CMP 48/80 during intravital microscopy. The extent of cell injury was determined using a fluorescent cell-viability indicator, propidium iodide (PI). In an additional group, mast cell degranulation with CMP 48/80 was prevented by using the mast cell stabilizer Ketotifen., Results: After a reduction in the number of circulating leukocytes, mast cell degranulation produced a mild increase in parenchymal cell injury. The injury levels significantly increased when individual regions of the mesentery were compared. Stabilization of the mast cells with Ketotifen reduced the injury to below baseline values., Conclusions: In the absence of leukocyte adhesion to the endothelium, mast cell degranulation contributes to parenchymal cell injury in the mesentery.

The mechanisms contributing to organ injury in hypertension have been incompletely defined. The thymus gland of the spontaneously hypertensive rat (SHR) shows significant atrophy at the age of 15 wk compared with its normotensive control, the Wistar-Kyoto rat (WKY). The aim of the present study was to examine the thymus of SHR for evidence of DNA nicking as one of the mechanisms for thymic atrophy. SHR and WKY were subjected to adrenalectomy or sham surgery at 12 wk and studied at 15 wk. Adrenalectomy served to normalize the blood pressure in the SHR. DNA nicking was detected by in situ nick-end labeling (ISEL) of fixed tissue sections. Tissue sections were treated with proteolysis, and terminal deoxyribonucleotidyl transferase was used to incorporate biotinylated deoxynucleotides into DNA nick end in situ. Separately, DNA fragmentation was evaluated by measuring the level of released mono- and oligonucleosomes to the cytoplasm. A higher number of thymic ISEL-positive cells and a higher level of cytoplasmic mono- and oligonucleosomes were observed in SHR than in WKY. After adrenalectomy the enhanced level of ISEL and cytoplasmic mono- and oligonucleosomes in SHR was reduced to the level in WKY. Dexamethasone treatment (0.05 mg. kg-1. day-1) in WKY serves to decrease the thymus weight and significantly elevate the level of mono- and oligonucleosomes. Thus increased DNA fragmentation represents one of the mechanisms associated with thymic atrophy, a feature that reflects immune suppression in SHR.

One of the hallmarks of venous insufficiency is an elevated venous pressure. While a number of mechanisms have been proposed for vascular and parenchymal cell damage following venous pressure elevation, such as white cell infiltration, a key question remains as to what degree venous occlusion and flow interruption per se may constitute a risk factor in venous disease. To gain an insight into this mechanism, we examined the effect of venous occlusion followed by reperfusion. A draining venule (circa 50 micrometer) in the rat mesentery was occluded with a micropipette (1 h) followed by reperfusion (1 h). The procedure serves to raise the microvascular pressure to about 31 mm Hg during the occlusion while the flow is completely stopped in the local venous and capillary network. Parenchymal cell death in the mesentery was monitored by propidium iodide (PI) labeling. The number of PI-positive cells significantly increased predominantly during reperfusion. A 1-week treatment with a micronized purified flavonoid fraction (100 mg/kg/day) served to significantly reduce parenchymal cell death as well as leukocyte rolling, adhesion to postcapillary venule, and migration into the tissue both during occlusion and reperfusion. The results indicate, that even in an initially symptomless tissue, flow reduction combined with microvascular pressure elevation during venous occlusion results in tissue damage not only during reperfusion (as in arterial occlusion) but also during occlusion.

Recent evidence in vivo indicates that spontaneously hypertensive rats (SHR) exhibit an increase in oxyradical production in and around microvascular endothelium. This study is aimed to examine whether xanthine oxidase plays a role in overproduction of oxidants and thereby may contribute to hypertensive states as a consequence of the increasing microvascular tone. The xanthine oxidase activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that depletes molybdenum as a cofactor for the enzyme activity as well as by administration of (-)BOF4272 [(-)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo(1,5-alpha)-1,3, 5-triazine-4-monohydrate], a synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY) rats displayed no significant alteration in the pressure. Multifunctional intravital videomicroscopy in mesentery microvessels with hydroethidine, an oxidant-sensitive fluoroprobe, showed that SHR endothelium exhibited overproduction of oxyradicals that coincided with the elevated arteriolar tone as compared with WKY rats. The tungsten diet significantly repressed these changes toward the levels observed in WKY rats. The activity of oxyradical-producing form of xanthine oxidase in the mesenteric tissue of SHR was approximately 3-fold greater than that of WKY rats, and pretreatment with the tungsten diet eliminated detectable levels of the enzyme activity. The inhibitory effects of the tungsten diet on the increasing blood pressure and arteriolar tone in SHR were also reproducible by administration of (-)BOF4272. These results suggest that xanthine oxidase accounts for a putative source of oxyradical generation that is associated with an increasing arteriolar tone in this form of hypertension.