Photodriven Charge Separation and Transport in Self‐Assembled Zinc Tetrabenzotetraphenylporphyrin and Perylenediimide Charge Conduits

Zinc tetrabenzotetraphenyl porphyrin (ZnTBTPP) covalently attached to four perylenediimide (PDI) acceptors self‐assembles into a π‐stacked, segregated columnar structure, as indicated by small‐ and wide‐angle X‐ray scattering. Photoexcitation of ZnTBTPP rapidly produces a long‐lived electron–hole pair having a 26 Å average separation distance, which is much longer than if the pair is confined within the covalent monomer. This implies that the charges are mobile within their respective segregated ZnTBTPP and PDI charge conduits.     

Mechanically stabilized tetrathiafulvalene radical dimers

Two donor-acceptor [3]catenanes-composed of a tetracationic molecular square, cyclobis(paraquat-4,4'-biphenylene), as the π-electron deficient ring and either two tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) containing macrocycles or two TTF-butadiyne-containing macrocycles as the π-electron rich components-have been investigated in order to study their ability to form TTF radical dimers. It has been proven that the mechanically interlocked nature of the [3]catenanes facilitates the formation of the TTF radical dimers under redox control, allowing an investigation to be performed on these intermolecular interactions in a so-called "molecular flask" under ambient conditions in considerable detail. In addition, it has also been shown that the stability of the TTF radical-cation dimers can be tuned by varying the secondary binding motifs in the [3]catenanes. By replacing the DNP station with a butadiyne group, the distribution of the TTF radical-cation dimer can be changed from 60% to 100%. These findings have been established by several techniques including cyclic voltammetry, spectroelectrochemistry and UV-vis-NIR and EPR spectroscopies, as well as with X-ray diffraction analysis which has provided a range of solid-state crystal structures. The experimental data are also supported by high-level DFT calculations. The results contribute significantly to our fundamental understanding of the interactions within the TTF radical dimers.     

Magnetic field-induced switching of the radical-pair intersystem crossing mechanism in a donor-bridge-acceptor molecule for artificial photosynthesis

A covalent, fixed-distance donor-bridge-acceptor (D-B-A) molecule was synthesized that upon photoexcitation undergoes ultrafast charge separation to yield a radical ion pair (RP) in which the spin-spin exchange interaction (2J) between the two radicals is sufficiently large to result in preferential RP intersystem crossing to the highest-energy RP eigenstate (T(+1)) at the 350 mT magnetic field characteristic of X-band (9.5 GHz) EPR spectroscopy. This behavior is unprecedented in covalent D-B-A molecules, and is evidenced by the time-resolved EPR (TREPR) spectrum at X-band of (3*)D-B-A derived from RP recombination, which shows all six canonical EPR transitions polarized in emission (e,e,e,e,e,e). In contrast, when the RP is photogenerated in a 3400 mT magnetic field, the TREPR triplet spectrum at W-band (94 GHz) of (3*)D-B-A displays the (a,e,e,a,a,e) polarization pattern characteristic of a weakly coupled RP precursor, similar to that observed in photosynthetic reaction center proteins, and indicates a switch to selective population of the lower-energy T(0) eigenstate.     

A Potent Leukocyte Transmigration Blocker: GT-73 Showed a Protective Effect against LPS-Induced ARDS in Mice

We recently developed a molecule (GT-73) that blocked leukocyte transendothelial migration from blood to the peripheral tissues, supposedly by affecting the platelet endothelial cell adhesion molecule (PECAM-1) function. GT-73 was tested in an LPS-induced acute respiratory distress syndrome (ARDS) mouse model. The rationale for this is based on the finding that the mortality of COVID-19 patients is partly caused by ARDS induced by a massive migration of leukocytes to the lungs. In addition, the role of tert-butyl and methyl ester moieties in the biological effect of GT-73 was investigated. A human leukocyte, transendothelial migration assay was applied to validate the blocking effect of GT-73 derivatives. Finally, a mouse model of LPS-induced ARDS was used to evaluate the histological and biochemical effects of GT-73. The obtained results showed that GT-73 has a unique structure that is responsible for its biological activity; two of its chemical moieties (tert-butyl and a methyl ester) are critical for this effect. GT-73 is a prodrug, and its lipophilic tail covalently binds to PECAM-1 via Lys536. GT-73 significantly decreased the number of infiltrating leukocytes in the lungs and reduced the inflammation level. Finally, GT-73 reduced the levels of IL-1β, IL-6, and MCP-1 in bronchoalveolar lavage fluid (BALF). In summary, we concluded that GT-73, a blocker of white blood cell transendothelial migration, has a favorable profile as a drug candidate for the treatment of ARDS in COVID-19 patients.     

Structure and dynamics of photogenerated triplet radical ion pairs in DNA hairpin conjugates with anthraquinone end caps

A series of DNA hairpins (AqGn) possessing a tethered anthraquinone (Aq) end-capping group were synthesized in which the distance between the Aq and a guanine-cytosine (G-C) base pair was systematically varied by changing the number (n - 1) of adenine-thymine (A-T) base pairs between them. The photophysics and photochemistry of these hairpins were investigated using nanosecond transient absorption and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. Upon photoexcitation, (1*)Aq undergoes rapid intersystem crossing to yield (3*)Aq, which is capable of oxidizing purine nucleobases resulting in the formation of (3)(Aq(-?)Gn(+?)). All (3)(Aq(-?)Gn(+?)) radical ion pairs exhibit asymmetric TREPR spectra with an electron spin polarization phase pattern of absorption and enhanced emission (A/E) due to their different triplet spin sublevel populations, which are derived from the corresponding non-Boltzmann spin sublevel populations of the (3*)Aq precursor. The TREPR spectra of the (3)(Aq(-?)Gn(+?)) radical ion pairs depend strongly on their spin-spin dipolar interaction and weakly on their spin-spin exchange coupling. The anisotropy of (3)(Aq(-?)Gn(+?)) makes it possible to determine that the π systems of Aq(-?) and G(+?) within the radical ion pair are parallel to one another. Charge recombination of the long-lived (3)(Aq(-?)Gn(+?)) radical ion pair displays an unusual bimodal distance dependence that results from a change in the rate-determining step for charge recombination from radical pair intersystem crossing for n < 4 to coherent superexchange for n > 4.     

Fast photodriven electron spin coherence transfer: a quantum gate based on a spin exchange j-jump

Photoexcitation of the electron donor (D) within a linear, covalent donor-acceptor-acceptor molecule (D-A(1)-A(2)) in which A(1) = A(2) results in sub-nanosecond formation of a spin-coherent singlet radical ion pair state, (1)(D(+?)-A(1)(-?)-A(2)), for which the spin-spin exchange interaction is large: 2J = 79 ± 1 mT. Subsequent laser excitation of A(1)(-?) during the lifetime of (1)(D(+?)-A(1)(-?)-A(2)) rapidly produces (1)(D(+?)-A(1)-A(2)(-?)), which abruptly decreases 2J 3600-fold. Subsequent coherent spin evolution mixes (1)(D(+?)-A(1)-A(2)(-?)) with (3)(D(+?)-A(1)-A(2)(-?)), resulting in mixed states which display transient spin-polarized EPR transitions characteristic of a spin-correlated radical ion pair. These photodriven J-jump experiments show that it is possible to use fast laser pulses to transfer electron spin coherence between organic radical ion pairs and observe the results using an essentially background-free time-resolved EPR experiment.     

Detection of Cyclo‐N5− in THF Solution

Compelling evidence has been found for the formation and direct detection of the cyclopentazole anion (cyclo‐N₅^?) in solution. The anion was prepared from phenylpentazole in two steps: reduction by an alkali metal to form the phenylpentazole radical anion, followed by thermal dissociation to yield cyclo‐N₅^?. The reaction solution was analyzed by HPLC coupled with negative mode mass spectrometry. A signal with m/z 70 was eluted about 2.1 min after injection of the sample. Its identification as N₅ was supported by single and double labeling with ¹⁵N, which yielded signals at m/z=71 and 72, respectively, with identical retention times in the HPLC column. MS/MS analysis of the m/z=70 signal revealed a dissociation product with m/z=42, which can be assigned to N₃^?. To our knowledge this is the first preparation of cyclo‐N₅^? in the bulk. The compound is indefinitely stable at temperatures below ?40 °C, and has a half‐life of a few minutes at room temperature.     

W-band31P-ENDOR on the high-affinity Mn2+ binding site in the minimal and tertiary stabilized hammerhead ribozymes

The catalytic activity of the tertiary stabilized hammerhead ribozyme (tsHHRz) is by three orders of magnitude higher than the one of the long-known minimal construct (mHHRz). This gives rise to the question whether the single high-affinity manganese(II) binding site present in both ribozymes is located closer to the cleavage site and the transition state in the tsHHRz than in the mHHRz, which would make a direct involvement of this metal(II) ion in the bond-breaking step more likely. Here, we used W-band³¹P-Davies-ENDOR (electron-nuclear double resonance) to complement earlier reported¹⁴N-ESEEM/HYSCORE (electron spin echo envelope modulation/hyperfine sublevel correlation) studies. The³¹P-ENDOR spectrum of the mHHRz revealed a doublet with a splitting of 8.4(±0.5) MHz but unresolved hyperfine anisotropy. Such a large splitting indicates an inner-sphere coordination of a phosphate backbone group with a significant amount of spin density on the phosphorous nucleus. This is in good agreement with the³¹P isotropic hyperfine constant,A _iso(³¹P), of +7.8 MHz obtained by density functional theory calculations on the structure of the Mn²⁺ binding site as found in crystals of the same ribozyme. This supports the idea that the structure and location of the binding site in the mHHRz is in frozen buffer similar to that found in the crystal. Since the W-band ENDOR spectrum of the tsHHRz also shows a³¹P splitting of 8.4(±0.5) MHz, the local structures of both binding sites appear to be similar, which agrees with the coincidence of the¹⁴N data. An involvement of the high-affinity Mn²⁺ ion in the catalytic step seems therefore unlikely.     

A multistate switchable [3]rotacatenane

Rotacatenanes are exotic molecular compounds that can be visualized as a unique combination of a [2]catenane and a [2]rotaxane, thereby combining both the circumrotation of the ring component (rotary motion) and the shuttling of the dumbbell component (translational motion) in one structure. Herein, we describe a strategy for the synthesis of a new switchable [3]rotacatenane and the investigation of its switching properties, which rely on the formation of tetrathiafulvalene (TTF) radical π-dimer interactions-namely, the mixed-valence state (TTF(2) )(+.) and the radical-cation dimer state (TTF(+.) )(2) -under ambient conditions. A template-directed approach, based on donor-acceptor interactions, has been developed, resulting in an improved yield of the key precursor [2]catenane, prior to rotacatenation. The nature of the binding between the [2]catenane and selected π-electron-rich templates has been elucidated by using X-ray crystallography and UV/Vis spectroscopy as well as isothermal titration microcalorimetry. The multistate switching mechanism of the [3]rotacatenane has been demonstrated by cyclic voltammetry and EPR spectroscopy. Most notably, the radical-cation dimer state (TTF(+.) )(2) has been shown to enter into an equilibrium by forming the co-conformation in which the two 1,5-dioxynaphthalene (DNP) units co-occupy the cavity of tetracationic cyclophane, thus enforcing the separation of TTF radical-cation dimer (TTF(+.) )(2) . The population ratio of this equilibrium state was found to be 1:1. We believe that this research demonstrates the power of constructing complex molecular machines using template-directed protocols, enabling us to make the transition from simple molecular switches to their multistate variants for enhancing information storage in molecular electronic devices.