Spin Delocalization Research Articles

Ligand-Based Radical Reactivity of Metal Thiosemicarbazones Prompts the Identification of Platinum(II)-Based Cytoprotectants.

CuATSM, a copper(II) complex of a bis(thiosemicarbazone) of diacetyl, prevents oxidative cell death and acts as a neuroprotectant in vivo, prompting its evaluation to treat amyotrophic lateral sclerosis and other neurodegenerative conditions in the clinic. We recently demonstrated that CuATSM functions as a potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation and associated ferroptotic cell death by a noncanonical mechanism based on radical addition to the ligand backbone. Herein we report our investigations of the generality of this reactivity, which include studies of corresponding complexes of various other metals, including Co, Ru, Ni, Pd, Pt, and Au. Inhibited autoxidations of styrene and dioxane reveal that most of these complexes exhibit RTA activity, consistent with ligand-based reactivity, but the identity of the metal atom nevertheless plays a role. In particular, analyses of the electronic structures of the complexes of metals within the same group (i.e., the group 10 metals Ni, Pd and Pt) highlight how the metal atom can modulate the ligand-based reactivity by enabling spin delocalization to the other thiosemicarbazone moiety. The RTA activity determined in organic solution largely translates to phospholipid bilayers and mammalian cells, where most complexes inhibited lipid peroxidation and associated ferroptotic cell death. A preliminary structure-activity study revealed Pt complexes with potencies eclipsing those of archetype ferroptosis inhibitors ferrostatin-1 and liproxstatin-1, suggesting that Pt (and to a lesser extent Ni) bis(thiosemicarbazone)s may be better suited to optimization for therapeutic development than those based on Cu.

Evidence for the formation of 6PPD-quinone from antioxidant 6PPD by cytochrome P450

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) as a rubber antioxidant has attracted global concern, since its ozone-oxidation product 6PPD-quinone (6PPDQ) was found to be the primary toxicant responsible for urban runoff mortality syndrome in coho salmon. However, the biotransformation fate and associated toxicological mechanism of 6PPD have not received much study yet. In this work, the in vitro assays showed 6PPD can be transformed into 6PPDQ by cytochromes P450 (CYP450) in human liver microsomes (HLMs) with 0.98 % production rate, and the adducts of 6PPDQ with calf thymus DNA and the N-N coupling product between 6PPD and 6PPDQ were further identified after 6PPD incubation in HLMs. Further evidence for the 6PPDQ formation can be obtained from the in vivo assays that the 6PPDQ-DNA adducts and 6PPD-N-N-6PPDQ dimer were detected in mice by oral gavage with 6PPD, and the latter dimer species was detected as well in 6PPD exposure to zebrafish larvae. Especially, the bioaccumulation property and high reactivity of 6PPDQ result in the continuous formation of the significant DNA adducts and 6PPD-N-N-6PPDQ dimer even in case of low production rate of biotransformation of 6PPD to 6PPDQ, which may provide potentially effective biomarkers for such process. DFT computations revealed the formation mechanism of 6PPDQ is the (N)H-abstraction of 6PPD by CYP450, followed by amino radical rebound at the nearby ortho-carbon, yielding a quinol intermediate due to spin delocalization, that might readily undergo further oxidation by CYP450 into 6PPDQ.

Site‐selective Photoredox‐Catalyzed Late‐stage Benzylic Hydrogen Isotope Exchange

A highly regioselective visible light photoredox‐catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst in combination with a thiol‐based hydrogen atom transfer catalyst, while the use of D2O as an isotope source ensures operational simplicity and cost‐effectiveness. High reactivity has been achieved for electron‐rich benzylic positions. Moreover, targeted radical formation enables unprecedented selective HIE on intramolecular competing benzylic and alpha to heteroatom positions with moderate to excellent deuterium incorporation. The utility of the reaction was demonstrated on the late‐stage HIE of several natural compounds and drug derivatives. Experimental studies and density functional theory (DFT) calculations suggested a single electron transfer (SET) mechanism followed by deprotonation to generate the benzylic radical, and revealed the importance of halogenated solvents or additives. Upon a weak complexation of the halogenated species to the substrate, an oxidation potential lowering effect is induced, as well as a stabilization of the radical‐cation species through spin delocalization.

Site-selective Photoredox-Catalyzed Late-stage Benzylic Hydrogen Isotope Exchange.

A highly regioselective visible light photoredox-catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst in combination with a thiol-based hydrogen atom transfer catalyst, while the use of D2O as an isotope source ensures operational simplicity and cost-effectiveness. High reactivity has been achieved for electron-rich benzylic positions. Moreover, targeted radical formation enables unprecedented selective HIE on intramolecular competing benzylic and alpha to heteroatom positions with moderate to excellent deuterium incorporation. The utility of the reaction was demonstrated on the late-stage HIE of several natural compounds and drug derivatives. Experimental studies and density functional theory (DFT) calculations suggested a single electron transfer (SET) mechanism followed by deprotonation to generate the benzylic radical, and revealed the importance of halogenated solvents or additives. Upon a weak complexation of the halogenated species to the substrate, an oxidation potential lowering effect is induced, as well as a stabilization of the radical-cation species through spin delocalization.

Tuning the Spin Interaction in Nonplanar Organic Diradicals through Mechanical Manipulation.

Open-shell polycyclic aromatic hydrocarbons (PAHs) represent promising building blocks for carbon-based functional magnetic materials. Their magnetic properties stem from the presence of unpaired electrons localized in radical states of π character. Consequently, these materials are inclined to exhibit spin delocalization, form extended collective states, and respond to the flexibility of the molecular backbones. However, they are also highly reactive, requiring structural strategies to protect the radical states from reacting with the environment. Here, we demonstrate that the open-shell ground state of the diradical 2-OS survives on a Au(111) substrate as a global singlet formed by two unpaired electrons with antiparallel spins coupled through a conformational-dependent interaction. The 2-OS molecule is a "protected" derivative of the Chichibabin's diradical, featuring a nonplanar geometry that destabilizes the closed-shell quinoidal structure. Using scanning tunneling microscopy (STM), we localized the two interacting spins at the molecular edges, and detected an excited triplet state a few millielectronvolts above the singlet ground state. Mean-field Hubbard simulations reveal that the exchange coupling between the two spins strongly depends on the torsional angles between the different molecular moieties, suggesting the possibility of influencing the molecule's magnetic state through structural changes. This was demonstrated here using the STM tip to manipulate the molecular conformation, while simultaneously detecting changes in the spin excitation spectrum. Our work suggests the potential of these PAHs as all-carbon spin-crossover materials.

Recent advances of 5-endo-trig radical cyclization: promoting strategies and applications.

5-endo-trig radical cyclization has long been recognized as one of the most straightforward ways for the construction of densely functionalized five-membered rings. Nevertheless, according to Baldwin's rules, the 5-endo-trig radical cyclization is kinetically disfavored due to stereoelectronic effects and thus usually proceeds via a slow rate, which renders its application a challenging task. In recent years, with the emergence of efficient radical generation methods and effective cyclization strategies, 5-endo-trig radical cyclization has been successfully accelerated to a synthetically useful rate and has been utilized in the access of diverse five-membered carbo- and heterocyclic compounds. This review comprehensively summarizes the methodologies involving the 5-endo-trig radical cyclization process, with particular emphasis on the elucidation of the promoting strategies, which include the polar effect, geometrical constraints, spin delocalization effect, and persistent radical effect. Each of these strategies is discussed in detail, with illustrative examples from recent literature studies to highlight their practical applications and effectiveness. It is anticipated that the in-depth understanding of the 5-endo-trig radical cyclization provided by this review would inspire further innovation of this privileged reaction mode and expand its applications. Moreover, the potent ring-closure-promoting strategies revealed herein would also contribute to achieving other challenges of cyclizations with particular significance for organic synthesis.

Isolation of Elusive Fluoflavine Radicals in Two Differing Oxidation States.

Facile access and switchability between multiple oxidation states are key properties of many catalytic applications and spintronic devices yet poorly understood due to inherent complications arising from isolating a redox system in multiple oxidation states without drastic structural changes. Here, we present the first isolable, free fluoflavine (flv) radical flv(1-•) as a bottleable potassium compound, [K(crypt-222)](flv•), 1, and a new series of organometallic rare earth complexes [(Cp*2Y)2(μ-flvz)]X, (where Cp* = pentamethylcyclopentadienyl, X = [Al(OC{CF3}3)4]- (z = -1), 2; X = 0 (z = -2), 3; [K(crypt-222)]+ (z = -3), 4) comprising the flv ligand in three different oxidation states, two of which are paramagnetic flv1-• and flv3-•. Excitingly, 1, 2, and 4 constitute the first isolable flv1-• and flv3-• radical complexes and, to date, the only isolated flv radicals of any oxidation state. All compounds are accessible in good crystalline yields and were unambiguously characterized via single-crystal X-ray diffraction analysis, cyclic voltammetry, IR-, UV-vis, and variable-temperature EPR spectroscopy. Remarkably, the EPR spectra for 1, 2, and 4 are distinct and a testament to stronger spin delocalization onto the metal centers as a function of higher charge on the flv radical. In-depth analysis of the electron- and spin density via density functional theory (DFT) calculations utilizing NLMO, QTAIM, and spin density topology analysis confirmed the fundamental interplay of metal coordination, ligand oxidation state, aromaticity, covalency, and spin density transfer, which may serve as blueprints for the development of future spintronic devices, single-molecule magnets, and quantum information science at large.

Theoretical Insight of Structural Effects on Bridge Mononitration of Tetrasubstituted p‐tert‐Butylcalix[4]Arenes

AbstractIn order to deeply understand calix[4]arene bridge mononitration, four representative tetrasubstituted p‐tert‐butylcalix[4]arenes were selected as substrates to theoretically explore calix[4]arene structural effects. Based on our proposed mechanism, the four corresponding calix[4]arene bridge radicals were artificially constructed. Then, three different levels of density functional theory (DFT) were used to calculate their pertinent species energies in radical generations and radical spin densities. The nitration differences of these four substrates were tentatively interpreted through comparison of their reaction activation energies in radical generations and radical stability. As a result, Gibbs activation free energies in radical generations cannot rationally interpret their nitration behaviors while radical stability can, which are characterized with radical stability energies (RSEs) and center carbon spin densities (SDcs). From radical structural analysis, it can be concluded that aromatic ring inversion is remarkably beneficial to enhance calix[4]arene bridge radical stability through strengthening spin delocalization onto their connecting aromatic rings, whereas a substituent with large steric hindrance is unbeneficial due to weakening spin delocalization. The theoretical analysis of radical intrinsic structural effects on their spin delocalizations provides guidance in designing new efficient calix[4]arene‐based substrates.

Antioxidant Activity of MgSO4 Ion Pairs by Spin-Electron Stabilization of Hydroxyl Radicals through DFT Calculations: Biological Relevance.

Magnesium sulfate has been of great interest as an antioxidant for its ability to decrease the oxidizing capacity of the hydroxyl radical. Previously, it was shown that the contact ion pair of this salt could stabilize •OH by coordinating with Mg and delocalizing the unpaired electron over sulfate. The present study explores in detail the MgSO4 antioxidant properties, considering all its ion pairs with •OH in different conformations. The analyses were based on structural, spin, and energetic properties using the DFT approach. As a result, the high antioxidant potential of MgSO4 is related to the spin-electron transfer from SO4 -2 to •OH causing electron spin delocalization and electrostatic stabilization. This transfer occurs for all ion pairs when •OH approaches the Mg first solvation shell, without being coordinated to Mg. The direct Mg-•OH interaction further stabilizes the radical system. These results show that spin-electron transfers are feasible in all hydrated ion pairs MgSO4-•OH, even at a •OH-sulfate distance greater than 10 Å.

(η8-Cyclooctatetraene)(η5-fluorenyl)titanium: a processable molecular spin qubit with optimized control of the molecule-substrate interface.

Depositing single paramagnetic molecules on surfaces for sensing and quantum computing applications requires subtle topological control. To overcome issues that are often encountered with sandwich metal complexes, we exploit here the low symmetry architecture and suitable vaporability of mixed-sandwich [FluTi(cot)], Flu = fluorenyl, cot = cyclooctatetraene, to drive submonolayer coverage and select an adsorption configuration that preserves the spin of molecules deposited on Au(111). Electron paramagnetic resonance spectroscopy and ab initio quantum computation evidence a d z 2 ground state that protects the spin from phonon-induced relaxation. Additionally, computed and measured spin coherence times exceed 10 μs despite the molecules being rich in hydrogen. A thorough submonolayer investigation by scanning tunneling microscopy, X-ray photoelectron and absorption spectrocopies and X-ray magnetic circular dichroism measurements supported by DFT calculations reveals that the most stable configuration, with the fluorenyl in contact with the metal surface, prevents titanium(iii) oxidation and spin delocalization to the surface. This is a necessary condition for single molecular spin qubit addressing on surfaces.

The influence of phosphine ligands on the redox properties of 1,4-divinylanthrylene-bridged diruthenium complexes and a derived macrocyclic analog

We report on a series of dinuclear 1,4-divinylanthrylene-bridged diruthenium complexes 1A-Ru-PR3 with different phosphine ligands (PiPr3, PiPr2Me, PPh3, and PMe3) and with coordination numbers of five or six. All compounds were characterized by NMR spectroscopy, high resolution ESI-MS and, in the case of 1A-Ru-PiPr3 and 1A-Ru-PMe3, single crystal X-ray diffraction. Cyclic voltammetry measurements reveal that the PR3 ligands, besides tuning the redox potentials, exert a strong influence on the stability of their one- and two-electron oxidized forms. Information on the charge- and spin-density distribution was obtained by IR, UV/Vis/NIR and EPR spectroscopy. Our results indicate full charge and spin delocalization in 1A-Ru-PiPr3•+, 1A-Ru-PMe3•+ and macrocyclic, isophthalate-bridged 2A-Ru-PiPr2Me••2+, whereas 1A-Ru-PiPr2Me•+ constitutes a peculiar case, where valence-delocalized and valence-localized structures seem to coexist.

Exchange Couplings and Magneto‐Structural Correlations of Trinuclear MII‐UIV‐MII (MII=Co, Ni, Cu) Complexes

AbstractThe magnetic properties of the trinuclear Schiff base complexes M2UL7 (MII=Co, Ni, Cu; L7=N,N’‐bis(3‐hydroxysalicylidene)‐2,2‐dimethyl‐1,3‐propanediamine), exhibiting the [M(μ‐O)2]2U core structure (3d‐5 f‐3d subsystem), have been investigated theoretically using scalar relativistic ZORA/DFT computations combined with the broken symmetry (BS) approach. The calculated coupling constants JMU between the adjacent M1−U and M2−U agree with the observed ferromagnetic (Ferro) character observed in the case of the Cu2UL7 complex, the antiferromagnetic (AF) character of the Ni2UL7 one is consistent with the experimentally observed AF behaviour for Co2UL7. The structural parameters, in particular the M−U distances and the M−Ob−U angles, as well as the electronic factors driving the superexchange couplings are discussed. The bond orders and the magnetic molecular orbital analyses reveal that the U(5 f) covalent contribution to the bonding within the M−O−U coordination is more important in the Co2UL7 and Ni2UL7 complexes than in the Cu2UL7 congener, thus favouring AF coupling between the transition metal and the uranium magnetic centers, in the first complexes. The analyses are supported by the study of the mixed ZnMUL7 and M2ThL7 systems, where the CoII (3d7) and NiII (3d8) paramagnetic ions are replaced by the diamagnetic ZnII(3d10) one, whereas in the second complex, the UIV(5f2) paramagnetic center is replaced by the diamagnetic ThIV(5f0) one. The Natural Populations Analyses confirm the crucial role of spin delocalization that is at work in favour of the AF vs. Ferro magnetic character of the M−U−M (M=Ni, Co) and Cu−U−Cu coordination, respectively.

High-valent actinyl (AnO2; An = U, Np and Pu) complexation with TEtraQuinoline (TEQ) ligand - a DFT study.

A recently synthesised novel macrocycle composed of four quinoline units called TEtraquinoline (TEQ) (J. Am. Chem. Soc., 2023, 145(4), 2609-2618) was reported to exhibit transition metal complexation ability. Meanwhile, there is a growing interest in different binding motifs for radioactive and toxic actinides. In this study, we modelled high-valent actinyl (AnO2)n+, An = U, Np, Pu; n = 1, 2, 3 complexes of TEQ and studied their geometric and electronic properties using scalar relativistic density functional theory (SR-DFT). The calculated results showed that the equatorial An-N and axial AnO bonds were polar bonds with a high degree of covalence, the former being longer than the latter. Natural bond orbital (NBO) analysis of the An-N bond orders decreased from complexes of uranyl to plutonyl and from complexes of heptavalent to pentavalent actinyls. This was due to the localization of the 5f orbital in the heavier actinyl and the high charge on An. The charge analysis showed a ligand-to-metal charge transfer (LMCT) on complexation. It was interesting to observe metal-to-ligand spin delocalization only in the [AnVI/VIIO2L]2+/3+ complexes, where the spin density on An was observed to increase on complexation. Based on the assigned oxidation states, it was observed that the heptavalent neptunyl cation retained its formal high oxidation state on complexation with TEQ. The energetics associated with the formation reaction of all the actinyl-TEQ complexes suggest spontaneity at lower temperatures (i.e., lower than 298.15 K). The energy decomposition analysis (EDA) indicates that the electrostatic energy contributions were predominant in the [AnVO2L]+ complexes, while covalent (orbital) energy contributions were higher in the [AnVIO2L]2+ and [AnVIIO2L]3+ complexes. The extended transition state-natural orbitals for chemical valence (ETS-NOCV) analysis confirmed the prominent covalent character in [AnVIIO2L]3+ over [AnVIO2L]2+ and [AnVO2L]+and the back donation of charges from An to N that stabilizes TEQ.

Electronic isomerism in a heterometallic nickel-iron-sulfur cluster models substrate binding and cyanide inhibition of carbon monoxide dehydrogenase.

The nickel-iron carbon monoxide dehydrogenase (CODH) enzyme uses a heterometallic nickel-iron-sulfur ([NiFe4S4]) cluster to catalyze the reversible interconversion of carbon dioxide (CO2) and carbon monoxide (CO). These reactions are essential for maintaining the global carbon cycle and offer a route towards sustainable greenhouse gas conversion but have not been successfully replicated in synthetic models, in part due to a poor understanding of the natural system. Though the general protein architecture of CODH is known, the electronic structure of the active site is not well-understood, and the mechanism of catalysis remains unresolved. To better understand the CODH enzyme, we have developed a protein-based model containing a heterometallic [NiFe3S4] cluster in the Pyrococcus furiosus (Pf) ferredoxin (Fd). This model binds small molecules such as carbon monoxide and cyanide, analogous to CODH. Multiple redox- and ligand-bound states of [NiFe3S4] Fd (NiFd) have been investigated using a suite of spectroscopic techniques, including resonance Raman, Ni and Fe K-edge X-ray absorption spectroscopy, and electron paramagnetic resonance, to resolve charge and spin delocalization across the cluster, site-specific electron density, and ligand activation. The facile movement of charge through the cluster highlights the fluidity of electron density within iron-sulfur clusters and suggests an electronic basis by which CN- inhibits the native system while the CO-bound state continues to elude isolation in CODH. The detailed characterization of isolable states that are accessible in our CODH model system provides valuable insight into unresolved enzymatic intermediates and offers design principles towards developing functional mimics of CODH.

NIR-absorbing and emitting α,α-nitrogen-bridged BODIPY dimers with strong excitonic coupling.

Three new distinct NIR α,α-NH-bridged BODIPY dimers were prepared by a direct nucleophilic substitution reaction. The synergistic effects of the nitrogen bridges and strong excitonic coupling between each BODIPY unit play major roles in enhancing the delocalization of an electron spin over the entire BODIPY dimers. The in situ formed aminyl radical dimer showed an absorption maximum at 1040 nm.

Spin characteristics in conjugated stable diradicals.

Spin properties are intrinsic characters of electrons. Radical molecules contain unpaired electron(s), and their unique chemical and physical properties make them an ideal platform for investigating spin properties in molecular systems. Among them, the burgeoning interest in stable conjugated diradicals is attributed to their distinctive characteristics, notably the dynamic resonance structures between open-shell and closed-shell forms, the malleability of their spin states, and the profound influence of intermolecular spin-spin interactions. A deep understanding of the spin characteristics of unpaired electrons in stable conjugated diradicals provides guidance for the design, synthesis, and characterization of radical-based materials. In this review, we discuss the unique spin delocalization, spin states, and spin-spin coupling characteristics of conjugated diradicals and emphasize how to precisely control these spin characteristics to understand their role in the molecules and as functional radical materials.

Crystal structure, magnetic properties and theoretical study of a bithiazolebis(oxamate)-containing [NiII3] helicate

New trinuclear Ni(ii) complex exhibiting intratrimer both weak ferro- and antiferromagnetic interactions resulting from the strict orthogonality between the magnetic orbitals, and a combination of spin delocalisation and spin polarisation mechanisms.

Electron and Spin Delocalization in [Co6 Se8 (PEt3 )6 ]0/+1 Superatoms.

Molecular clusters can function as nanoscale atoms/superatoms, assembling into superatomic solids, a new class of solid-state materials with designable properties through modifications on superatoms. To explore possibilities on diversifying building blocks, here we thoroughly studied one representative superatom, Co6 Se8 (PEt3 )6 . We probed its structural, electronic, and magnetic properties and revealed its detailed electronic structure as valence electrons delocalize over inorganic [Co6 Se8 ] core while ligands function as an insulated shell. 59 Co SSNMR measurements on the core and 31 P, 13 C on the ligands show that the neutral Co6 Se8 (PEt3 )6 is diamagnetic and symmetric, with all ligands magnetically equivalent. Quantum computations cross-validate NMR results and reveal degenerate delocalized HOMO orbitals, indicating aromaticity. Ligand substitution keeps the inorganic core nearly intact. After losing one electron, the unpaired electron in [Co6 Se8 (PEt3 )6 ]+1 is delocalized, causing paramagnetism and a delocalized electron spin. Notably, this feature of electron/spin delocalization over a large cluster is attractive for special single-electron devices.

Conjugation-Induced Spin Delocalization in Helical Chiral Carbon Radicals via Through-Bond and Through-Space Effects.

A class of highly stable hydrocarbon radicals with helical chirality are synthesized, which can be isolated and purified by routine column chromatography on silica gel. These carbon-centered radicals are stabilized by through-bond delocalization and intramolecular through-space conjugation, which is evidenced by Density Functional Theory (DFT) calculation. The high stability enables to directly modify the carbon radical via palladium-catalyzed cross-coupling with the radical being untapped. The structures and optoelectronic properties are investigated with a variety of experimental methods, including Electron Paramagnetic Resonance (EPR), Ultraviolet Visisble Near Infrared (UV-vis-NIR) measurements, Cyclic Voltammetry (CV), Thermogravimetry Analysis (TGA), Circular Dichroism (CD) spectra, High-Performance Liquid Chromatography (HPLC), and X-ray crystallographic analysis. DFT calculations indicated that the 9-anthryl helical radical is more stable than its tail-to-tail σ-dimer over 13.2kJmol-1 , which is consistent with experimental observations.

Bis-Olefin Based Crystalline Schlenk Hydrocarbon Diradicals with a Triplet Ground State.

A modular approach for the synthesis of isolable crystalline Schlenk hydrocarbon diradicals from m-phenylene bridged electron-rich bis-triazaalkenes as synthons is reported. EPR spectroscopy confirms their diradical nature and triplet electronic structure by revealing a half-field signal. A computational analysis confirms the triplet state to be the ground state. As a proof-of-principle for the modular methodology, the 4,6-dimethyl-m-phenylene was further utilized as a coupling unit between two alkene motifs. The steric conjunction of the 4,6-dimethyl groups substantially twists the substituents at the nonbonding electron bearing centers relative to the central coupling m-phenylene motif. As a result, the spin delocalization is decreased and the exchange coupling between the two unpaired spins, hence, significantly reduced. Notably, 108 years after Schlenk's m-phenylene-bis(diphenylmethyl) synthesis as a diradical, for the first time we were able to isolate its derivative with the same spacer, i.e. m-phenylene, between two radical centers in a crystalline form.