Toward New Horizons in Verdazyl-Nitroxide High-Spin Systems: Thermally Robust Tetraradical with Quintet Ground State.

High-spin organic tetraradicals with significant intramolecular exchange interactions have high potential for advanced technological applications and fundamental research, but examples reported to date exhibit limited stability and processability. In this work, we designed the first tetraradical based on an oxoverdazyl core and nitronyl nitroxide radicals and successfully synthesized it using a palladium-catalyzed cross-coupling reaction of an oxoverdazyl radical bearing three iodo-phenylene moieties with a gold(I) nitronyl nitroxide-2-ide complex in the presence of a recently developed efficient catalytic system. The molecular and crystal structures of the tetraradical were confirmed by single crystal X-ray diffraction analysis. The tetraradical possesses good thermal stability with decomposition onset at ∼125 °C in an inert atmosphere; in a toluene solution upon prolonged heating at 90 °C in air, no decomposition was observed. The resulting unique verdazyl-nitroxide conjugate was thoroughly studied using a range of experimental and theoretical techniques, such as SQUID magnetometry of polycrystalline powders, EPR spectroscopy in various matrices, cyclic voltammetry, and high-level quantum chemical calculations. All collected data confirm the high thermal stability of the resulting tetraradical and quintet multiplicity of its ground state, which makes the synthesis of this important paramagnet a new milestone in the field of creating high-spin systems.

Sweetened Alkylated Verdazyls Effectively Kill Cancer Cells under Light Irradiation.

The development of novel photo-dynamic therapy (PDT) agents enabling to treat the oxygen-deficient tumors is the emerging tasks for the modern medicinal chemistry. Herein, we describe the design and preparation of water-soluble agents for PDT which generate active radical species upon light irradiation. Two conjugates of carbohydrates with 1,2,4,6-substituted-1,4-dihydro-1,2,4,5-tetrazin-3(2H)-ones (AlkVZs) demonstrated high oxygen-independent cytotoxicity on PC-3 and Jurkat cancer cells under light irradiation combining with low toxicity in the dark. The efficacy of prepared compounds was estimated using MTT and Alamar Blue tests as well as microscopic dead/live colored images and flow cytometry. The analysis of obtained results reveals the influence of sugar moiety on the activity of AlkVZs. We believe that obtained compounds have high potency as platform for design of new agents for photo-dynamic therapy.

Alkylverdazyls as a Source of Alkyl Radicals for Light-Triggered Cancer Cell Death.

Two alkylated verdazyl radicals (AlkVZs) were investigated as active compounds for photoinitiated controlled MCF-7 cell death. Observed results unambiguously showed that AlkVZ could be a potential structural moiety for the design of a novel family of photodynamic therapy agents. The main advantage of the proposed substances is an oxygen-independent generation of active radicals, which play a pivotal role in the treatment of oxygen-deficient tumors.

Platform for High-Spin Molecules: A Verdazyl-Nitronyl Nitroxide Triradical with Quartet Ground State.

Thermally resistant air-stable organic triradicals with a quartet ground state and a large energy gap between spin states are still unique compounds. In this work, we succeeded to design and prepare the first highly stable triradical, consisting of oxoverdazyl and nitronyl nitroxide radical fragments, with a quartet ground state. The triradical and its diradical precursor were synthesized via a palladium-catalyzed cross-coupling reaction of diiodoverdazyl with nitronyl nitroxide-2-ide gold(I) complex. Both paramagnetic compounds were fully characterized by single-crystal X-ray diffraction analysis, superconducting quantum interference device magnetometry, EPR spectroscopy in various matrices, and cyclic voltammetry. In the diradical, the verdazyl and nitronyl nitroxide centers demonstrated full reversibility of redox process, while for the triradical, the electrochemical reduction and oxidation proceed at practically the same redox potentials, but become quasi-reversible. A series of high-level CASSCF/NEVPT2 calculations was performed to predict inter- and intramolecular exchange interactions in crystals of di- and triradicals and to establish their magnetic motifs. Based on the predicted magnetic motifs, the temperature dependences of the magnetic susceptibility were analyzed, and the singlet-triplet (135 ± 10 cm-1) and doublet-quartet (17 ± 2 and 152 ± 19 cm-1) splitting was found to be moderate. Unique high stability of synthesized verdazyl-nitronylnitroxide triradical opens new perspectives for further functionalization and design of high-spin systems with four or more spins.

Kinetic investigation of thermal and photoinduced homolysis of alkylated verdazyls.

The on-demand generation of stable organic radicals from the precursors can be considered as an essential challenge for the plethora of applications in various fields of science. In this contribution, we prepared a range of N-(methyl)benzyl derivatives of 6-oxoverdazyl via atom transfer radical addition from moderate to high yields and studied their thermal- and photo-initiated homolysis. The kinetics of homolysis was measured, and the dissociating rate constant kd, activation energy Ea and frequency factor A were estimated. Variation of the substituent at the C3-position of the verdazyl ring was successfully applied for fine-tuning the homolysis rate: the value of kd was higher for alkylverdazyls with electron-withdrawing groups, e.g., the para nitro group afforded a 6-fold increase in kd. In contrast to thermal homolysis, the rate of photoinduced decomposition depends on both the extinction coefficient and the value of activation energy. Thus, nitro-containing alkylated verdazyls show the highest homolysis rate in both types of initiations. The achieved results afford a novel opportunity in the controlled generation of verdazyls and further application of these compounds in medicine and chemical industry.

Ferromagnetically Coupled S=1 Chains in Crystals of Verdazyl-Nitronyl Nitroxide Diradicals.

Thermally stable organic diradicals with a triplet ground state along with large singlet-triplet energy gap have significant potential for advanced technological applications. A series of phenylene-bridged diradicals with oxoverdazyl and nitronyl nitroxide units were synthesized via a palladium-catalyzed cross-coupling reaction of iodoverdazyls with a nitronyl nitroxide-2-ide gold(I) complex with high yields. The diradicals exhibit high stability and do not decompose in an inert atmosphere up to 180 °C. For the diradicals, both substantial AF (ΔEST ≈-64 cm-1 ) and FM (ΔEST ≥25 and 100 cm-1 ) intramolecular exchange interactions were observed. The sign of the exchange interaction is determined both by the bridging moiety (para- or meta-phenylene) and by the type of oxoverdazyl block (C-linked or N-linked). Upon crystallization, diradicals with the triplet ground state form unique one-dimensional exchange-coupled chains with strong intra- and weak inter-diradical ferromagnetic coupling.

A Weakly Antiferromagnetically Coupled Biradical Combining Verdazyl with Nitronylnitroxide Units.

An antiferromagnetically (AFM) coupled biradical based on oxoverdazyl and nitronylnitroxide was synthesized in 46 % yield using Sonogashira coupling. The obtained heterobiradical evidenced distinct properties of both radical entities in solution. Depending on the solvent, the prepared biradical crystallized in two different forms. SQUID magnetization measurements on Form II showed coupling constants JintraII /kB =-2.1 K and zJinterII /kB =-11.5 K. Consequently, total intermolecular exchange interactions are five times larger than the intramolecular ones. Further, DFT calculations explained this phenomenon and indicated the advantage of Form I for further in-depth investigations.