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A series of pyridyl‐substituted nitronyl nitroxides was synthesized and structurally characterized. A comprehensive magnetochemical and quantum chemical study of extended raw of the nitroxides with different substituents R in the pyridine fragment was performed. It was shown, that temperature‐dependent magnetic properties are determined by the short contacts between nitroxide groups of adjacent molecules as well as between nitroxide group and methyl substituents in the pseudo axial positions of imidazoline fragments. Quantum chemistry allows to select the appropriate model of exchange cluster for analysis of experimental magnetic data and evaluation of the exchange interaction parameters. For NN–PyCl the "order‐disorder" transition was detected by means of low temperature XRD. The difference in the experimental and calculated exchange interaction energies may serve as an indicator of temperature‐induced structural rearrangements. For instance, for methyl substituted nitronyl nitroxide NN‐PyMe structural transformations and significant changes in exchange interaction energies were observed. [ABSTRACT FROM AUTHOR]

A novel synthetic approach has been employed to synthesize a series of new nitronyl nitroxides: 2‐(1‐propyl‐1H‐imidazol‐5‐yl)‐ (Ln−Pr), 2‐(1‐isopropyl‐1H‐imidazol‐5‐yl)‐ (Li−Pr) and 2‐(1‐butyl‐1H‐imidazol‐5‐yl)‐4,4,5,5‐tetramethyl‐4,5‐dihydro‐1H‐imidazole‐3‐oxide‐1‐oxyl (Ln−Bu). The reaction of Cu(hfac)2 with LR in a 1 : 2 ratio yields mononuclear heterospin complexes [Cu(hfac)2(LR)2] (LR=Ln‐Pr, Li‐Pr, Ln‐Bu), which have a similar crystal structure to the "jumping" crystals [Cu(hfac)2(LMe)2] that exhibit chemomechanical activity. It was shown that an increase in the alkyl substituent R leads to changes in the crystal packing of the molecules and the absence of chemomechanical activity. Furthermore, it was found that two polymorph modifications of the heterospin complex [Cu(hfac)2(Ln−Pr)2] can be obtained, and magnetic properties of [Cu(hfac)2(Ln−Pr)2] strongly depend on the angle between the planes of the paramagnetic fragment O•–N‐C=N→O and the imidazole ring in Ln−Pr. [ABSTRACT FROM AUTHOR]

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds LCF3 and LMe, with LMe inducing temporary bradycardia and hypotension specifically in female rats, and LCF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards β 1 adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders. [Display omitted] • Distinctive antiarrhythmic and hypotensive properties. • The third-positioned nitronyl nitroxide fragment is a must. • Gender variations in compound activity are observed. • Stable aqueous solutions and lower toxicity compared to established HNO donors. [ABSTRACT FROM AUTHOR]

Abstract: An approach to the synthesis of nitronyl nitroxide 2,2′-(buta-1,3-diyne-1,4-diyl)bis(4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole 3-oxide 1-oxyl) (4) was developed. Compound 4 is the first diradical with nitronyl nitroxide groups directly linked through a diacetylene fragment. In solid phase the diradicals are arranged in stacks with parallel Cts, with the distances between the terminal carbon atoms of the neighboring diacetylene groups (T and d) being 6.170 and 4.466Å, respectively, and the angle between the translation vector and the median line passing through the Ch name="sbnd" />Ct of 45.9°. The values of T and d are outside the range of structural criteria allowing a topochemical reaction. Thus UV irradiation does not initiate solid phase polymerization of 4. After exposure at 373K for 1h the crystals of 4 turn dark-brown, become X-ray amorphous and lose the majority of their paramagnetic centers without significantly changing their mass. Upon further heating up to 400–420K the product explodes, releasing about 360kJ/mol of heat. A diluted solution of 4 in 1,4-dioxane produces an EPR spectrum typical of a strong exchange (a multiplet of nine broadened lines with A 4N =0.35mT), indicating the efficiency of the Ch name="sbnd" />Ct as an exchange channel. The character of the experimental μ eff(T) dependence for 4 indicates a strong intramolecular antiferromagnetic-type exchange interaction (J/k B ∼−104K) and the dominating weak intermolecular ferromagnetic exchange. [Copyright &y& Elsevier]

Abstract: It was established that the reactions of pyrazol-3-yl-substituted nitronyl nitroxide (HL 1) and pyrazol-3-yl-substituted imino nitroxide (HL 3) with Cu(II) acetate lead to self-assembly of the Cu4(OH)2(OAc)4(DMF)2(L1)2 tetranuclear and Cu2(OAc)2(H2O)2(L3)2 dinuclear complexes, respectively. The reaction of Cu(II) acetate with 5-ethoxycarbonyl-pyrazol-3-yl-substituted nitronyl nitroxide (HL 2) gave unexpected solid Cu2(H2O)2(L6)2 ·2DMF, in which L 6 is a deprotonated 5-carboxy-pyrazol-3-yl-substituted nitronyl nitroxide, formed as a result of cleavage of an ester bond in the starting HL 2. A similar transformation of the paramagnetic ligand was observed in the reaction of Cu(II) acetate with 5-ethoxycarbonyl-pyrazol-3-yl-substituted imino nitroxide (HL 4). It led to the formation of Cu2(DMF)2(L7)2, where L 7 is deprotonated 2-(5-carboxy-1H-pyrazol-3-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole 3-oxide. An X-ray diffraction study indicated that in Cu4(OH)2(OAc)4(DMF)2(L1)2 and Cu2(OAc)2(H2O)2(L3)2, the L 1 and L 3 paramagnetic ligands perform the bridging cyclic tridentate function, while in Cu2(H2O)2(L6)2 ·2DMF and Cu2(DMF)2(L7)2, the paramagnetic L 6 and diamagnetic L 7 are bridging bicyclic tetradentate ligands. The magnetic behavior of complexes with coordinated nitronyl nitroxide – Cu4(OH)2(OAc)4(DMF)2(L1)2 and Cu2(H2O)2(L6)2 ·2DMF is dictated by the dominant antiferromagnetic exchange interactions, which is confirmed by quantum-chemical data. The magnetic susceptibility of Cu2(OAc)2(H2O)2(L3)2 reflects the competition between the antiferromagnetic and ferromagnetic components, of which the latter is due to electron coupling in the Cu(II)←N=C–N∸O exchange channels. EPR data confirm the results received from static magnetic measurements for multispin solids. [Copyright &y& Elsevier]

It is shown that SNH approach opens new possibilities in the synthesis of polyfunctional nitronyl and imino nitroxides. It is found that the interaction of 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl lithium salt Li1 with 3,6-diaryl-1,2,4-triazines leads to formation of the corresponding triazines bearing nitronyl nitroxide or imino nitroxide substituent at position 5 of the heterocycle. The reaction of Li1 with pyridazine-N-oxide gives rise to nitroxide with buten-3-ynyl substituent 5. Spin-labeled 5 could be readily transformed by the use of 1,3-dipolar and nucleophilic addition reactions, as well as oxidative coupling, that gives a large group of new paramagnets: 2-(1H-pyrazol-5-yl)vinyl-, 2-ethynylcyclopropyl-, 2-(3-(ethoxycarbonyl) isoxazol-5-yl)vinyl-, 1-(pyrrolidin-1-yl)but-3-ynyl-substituted nitronyl nitroxide and a diradical - 2,2'-((1E,7E)-octa-1,7-dien-3,5-diyne-1,8-diyl)bis(4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl). The new nitroxides were characterized by X-ray single crystal data, ESR and static magnetic susceptibility measurements. [ABSTRACT FROM AUTHOR]