Roman Yu. Peshkov

ZUSAMMENFASSUNG: Der Mechanismus der thermischen Z → E ‐Isomerisierung von Azobenzol und seinen Derivaten wird seit nahezu einem Jahrhundert kontrovers diskutiert; zur Erklärung des nichtlinearen Zusammenhangs der Reaktionsgeschwindigkeit von verschiedenen Substituenten wurden sowohl Inversions‐, Rotations‐ als auch nicht‐adiabatische Reaktionswege vorgeschlagen. In der vorliegenden Arbeit kombinieren wir eine systematische kinetische Analyse der Isomerisierungsreaktion mit temperaturabhängigen Eyring‐ und isokinetischen Auswertungen, um den Ursprung des beobachteten Verhaltens experimentell zu untersuchen. Die durchgängig negative Aktivierungsentropie, die so für eine Reihe para ‐substituierter Azobenzole gefunden wurde, deutet darauf hin, dass ein einheitlicher, nicht‐adiabatischer Rotationsmechanismus über alle Substituenten hinweg vorliegt. Wir konnten zeigen, dass die charakteristische „V‐förmige“ Hammett‐Korrelation von substituierten Azobenzolen nicht auf einen Mechanismuswechsel zurückzuführen ist, sondern auf die unzureichende Eignung der σ _p ‐Skala zur Beschreibung der Stabilisierung der open‐shell, diradikalartigen Spezies im nicht‐adiabatischen Reaktionspfad. Der Creary‐σ·‐Radikalparameter stellt die Linearität wieder her und bestätigt, dass sowohl elektronenschiebende als auch elektronenziehende Substituenten die Reaktionsgeschwindigkeit erhöhen, indem sie die diradikalartige Spezies stabilisieren. Quantenchemische Rechnungen mit unterschiedlichen Multireferenz‐, Spin‐Flip‐Ansätzen sowie Ansätzen mit inzelreferenz reproduzierten die beobachteten, experimentellen Tendenzen und stützten die Dominanz des nicht‐adiabatischen Reaktionspfads, wohingegen DFT diese Trends systematisch nicht reproduzieren konnte.

The mechanism of thermal Z → E isomerization in azobenzenes has been debated for nearly a century, with inversion, rotation, and nonadiabatic pathways proposed to account for the nonlinear substituent dependence of the reaction rate. Here, we combine systematic kinetic analysis with temperature‐dependent Eyring and isokinetic evaluations to experimentally evaluate the origin of this behavior. A series of para ‐substituted azobenzenes exhibits uniformly negative entropies of activation, suggesting a single nonadiabatic rotational mechanism is operative across all substituents. We found that the characteristic “V‐shaped” Hammett correlation of azobenzene arises not from a mechanistic change, but from the inadequacy of the σ _p scale to describe the stabilization of the open‐shell, diradicaloid species involved in the nonadiabatic pathway. The Creary σ· radical parameter restores linearity, confirming that both electron‐donating and electron‐withdrawing substituents increase the reaction rate, stabilizing the diradicaloid species. Complementary calculations using different multireference spin‐flip and single‐reference approaches reproduce the experimental trends and support the predominance of the nonadiabatic pathway, whereas density functional theory (DFT) systematically fails to reproduce these trends.

Nature uses protonation and microenvironmental effects to modulate photoisomerization, as seen in rhodopsins and GFP. Inspired by this, we report phosphaindirubin (PI), a visible‐light responsive photoswitch bearing a stereogenic phosphorus center that exhibits reversible Z / E isomerization controlled by light, acid, and nucleophiles. While structurally related to photoinert isoindigo, phosphaindirubin undergoes efficient Z → E isomerization in low‐polarity solvents but remains inert in polar media unless protonated. Acid gating alters the excited‐state landscape, enabling switching under light irradiation in acetonitrile. Strikingly, the thermal back‐isomerization of PI is accelerated by nucleophiles, including pyridine and iodide, offering an underexplored mechanism for catalyzing double bond rotation. This triple‐responsiveness to light, acid, and nucleophile enables reversible, fatigue‐resistant cycling between Z ‐ and E ‐forms. These findings introduce a new design principle for photoswitches based on dynamic, multi‐stimuli gating of excited‐state and ground‐state reactivity.

Nature uses protonation and microenvironmental effects to modulate photoisomerization, as seen in rhodopsins and GFP. Inspired by this, we report phosphaindirubin (PI), a visible‐light responsive photoswitch bearing a stereogenic phosphorus center that exhibits reversible Z / E isomerization controlled by light, acid, and nucleophiles. While structurally related to photoinert isoindigo, phosphaindirubin undergoes efficient Z → E isomerization in low‐polarity solvents but remains inert in polar media unless protonated. Acid gating alters the excited‐state landscape, enabling switching under light irradiation in acetonitrile. Strikingly, the thermal back‐isomerization of PI is accelerated by nucleophiles, including pyridine and iodide, offering an underexplored mechanism for catalyzing double bond rotation. This triple‐responsiveness to light, acid, and nucleophile enables reversible, fatigue‐resistant cycling between Z ‐ and E ‐forms. These findings introduce a new design principle for photoswitches based on dynamic, multi‐stimuli gating of excited‐state and ground‐state reactivity.

In this work, a semi‐automated pipeline for the transition state search of molecular switches (PiTS ³ ) is reported, which facilitates the search, optimization, and conformational analysis of transition states of user‐generated molecular structures. This tool is oriented towards the casual user interested in simulating the thermal properties of photochemical switches. Hence, the pipeline can easily read the commonly used .cdxml files as input, and leverages different established packages such as ORCA, xTB, CREST, and pysisyphus. Additional scripts are provided to combine different inputs to create libraries of compounds from chemical drawings, to explore large chemical spaces of photoswitches based on the stilbene, imine, aza‐diarylethene, and norbornadiene structures.

Structural properties, intra- and inter-ring interactions, and vibrational and optical spectra of a series of symmetric spirenes were investigated. The best candidate for opto-electronic applications was revealed.

Conventional spiro-linked conjugated materials are attractive for organic optoelectronic applications due to the unique combination of their optical and electronic properties. However, spiro-linked conjugated materials with conjugation extension directed along the main axis of the molecule are still only rare examples among the vast number of spiro-linked conjugated materials. Herein, the synthesis, leading to π-extended spiro-linked conjugated materials─spiro[4.4]nonane-1,6-diones and spiro[5.5]undecane-1,7-diones─has been developed and optimized. The proposed design concept starts from readily available malonic esters and contains several steps: double alkylation of malonic ester with bromomethylaryl(hetaryl)s; conversion of a malonic ester into the corresponding malonic acid; electrophilic spirocyclization of the latter into the annulated spiro[4.4]nonane-1,6-dione or spiro[5.5]undecane-1,7-dione in the presence of phosphorus pentoxide. On the basis of these insights, the developed method yielded spiro-linked conjugated cores fused with benzene, thiophene, and naphthalene, decorated with active halogen atoms. The structures of the synthesized spirocycles were determined by single-crystal X-ray diffraction analysis. Benzene fused spiro[4.4]nonane-1,6-dione decorated with bromine atoms was transformed into V-shape phenylene-thiophene co-oligomer type spirodimers via Stille coupling. The spiro-bis(4-n-dodecylphenyl)-2,2′-bithiophene derivative possessed high photoluminescence properties in both solution and solid state with a photoluminescence quantum yield (PL QY) of 38%.

A new ring opening reaction was found while attempting to isolate the imines from ortho‐heteroatom substituted anilines and camphor‐like bicyclic ketones. The benzoazoles containing a cyclopentanemethyl group at position 2 of the heterocycle were isolated instead of the expected imines. The detailed study of the transformation, including EPR experiments, revealed the most probable radical mechanism. The proposed reaction pathways were confirmed by quantum chemical calculations. The dichotomy of 1–2 and 2–3 bonds cleavage is discussed together with the evaluation of the stereochemical outcome of the reactions. The benzoazoles obtained via the new reaction are of particular interest for the medicinal chemistry.

We report on the design, synthesis and molecular modeling study of conjugates of adenosine diphosphate (ADP) and morpholino nucleosides as potential selective inhibitors of poly(ADP-ribose)polymerases-1, 2 and 3. Sixteen dinucleoside pyrophosphates containing natural heterocyclic bases as well as 5-haloganeted pyrimidines, and mimicking a main substrate of these enzymes, nicotinamide adenine dinucleotide (NAD+)-molecule, have been synthesized in a high yield. Morpholino nucleosides have been tethered to the β-phosphate of ADP via a phosphoester or phosphoramide bond. Screening of the inhibiting properties of these derivatives on the autopoly(ADP-ribosyl)ation of PARP-1 and PARP-2 has shown that the effect depends upon the type of nucleobase as well as on the linkage between ADP and morpholino nucleoside. The 5-iodination of uracil and the introduction of the P–N bond in NAD+-mimetics have shown to increase inhibition properties. Structural modeling suggested that the P–N bond can stabilize the pyrophosphate group in active conformation due to the formation of an intramolecular hydrogen bond. The most active NAD+ analog against PARP-1 contained 5-iodouracil 2ʹ-aminomethylmorpholino nucleoside with IC50 126 ± 6 μM, while in the case of PARP-2 it was adenine 2ʹ-aminomethylmorpholino nucleoside (IC50 63 ± 10 μM). In silico analysis revealed that thymine and uracil-based NAD+ analogs were recognized as the NAD+-analog that targets the nicotinamide binding site. On the contrary, the adenine 2ʹ-aminomethylmorpholino nucleoside-based NAD+ analogs were predicted to identify as PAR-analogs that target the acceptor binding site of PARP-2, representing a novel molecular mechanism for selective PARP inhibition. This discovery opens a new avenue for the rational design of PARP-1/2 specific inhibitors.