Location of the Shared Proton in Proton-Bound Dimer Compound of Hydrogen Sulfate and Formate: Path Integral Molecular Dynamics Study.

The structure of the proton-bound dimer compound of hydrogen sulfate and formate has been studied by considering nuclear quantum effects (NQEs) using the path integral molecular dynamics method. This study unveiled the location of the shared proton and answered the following question: "Is the shared proton localized on either an anion or located around the center of two anions?" We have elucidated that the shared proton is distributed in the region beyond the transition state due to the NQEs, even though the shared proton did not completely overcome the transition state for the proton shuttle.

Nuclear quantum and H/D isotope effects on intramolecular hydrogen bond in curcumin.

Curcumin and its derivatives possess intramolecular low-barrier hydrogen bonds for intramolecular proton transfer. The π-delocalization in the OCCCO framework of the hydrogen bond in these compounds is reorganized concomitantly with the proton transfer. To characterize the hydrogen bond and π-delocalization, we performed path integral molecular dynamics simulations, revealing that although the proton migration and reorganization of the π-delocalized structure showed a positive correlation, the correlation was weak.

Room-temperature Ia3̄d phase obtained for the binary mixture containing different sizes of siloxanyl terminals.

Two types of binary mixtures were examined to optimize the siloxanyl fraction by filling the gap between the two Cub-phase-forming molecules with di- and tri-siloxanyl terminals. Adding siloxanyl to the disiloxanyl system largely inhibited crystallization, increasing the stability at room temperature of the meta-stable Ia3̄d phase obtained by cooling from the high-temperature phase. The effect was prominent for the mixtures containing both di- and tri-siloxanyl compounds. The most prominent result was obtained for the 50 : 50 mixture; the Ia3̄d phase was quite stable and survived at room temperature after more than 1 year, as if it were like a thermodynamically stable phase.

Direct Elucidation of the Vibrationally Averaged Structure of Benzene: A Path Integral Molecular Dynamics Study.

Path integral molecular dynamics (PIMD) simulations for C6H6, C6D6, and C6T6 have been carried out to directly estimate the distribution of projected C-H(D,T) bond lengths onto the principal axis plane. The average values of raw C-H(D,T) bond lengths obtained from PIMD simulations are in the order of ⟨RC-H⟩ > ⟨RC-D⟩ > ⟨RC-T⟩ due to the anharmonicity of the potential energy curve. However, the projected C-H(D,T) bond lengths are almost the same as those reported by Hirano et al. [J. Mol. Struct. 2021, 1243, 130537]. Our PIMD simulations directly and strongly support the explanation by Hirano et al. for the experimental observations that almost the same projected C-H(D) bond lengths are found for C6H6 and C6D6. The PIMD simulations also predicted the same projected bond lengths for C6T6 as those of C6H(D)6. In addition to the previous local mode analysis, the present PIMD simulations predicted, for benzene isotopologues, that the vibrationally averaged structure is planar but non-flat.

Oxidative Functionalization of Catechol Derivatives Substituted with Electron-Withdrawing Groups.

Catechols possessing electron-withdrawing groups at the C3 position effectively underwent oxidative functionalization at the C4 position in the presence of phenyliodine(III) diacetate (PIDA) and heteroarene nucleophiles (e.g., indole, indazole, and benzotriazole) to produce the corresponding biaryl products. The PIDA-mediated oxidation of catechol derivatives afforded the ortho-benzoquinone intermediate, which subsequently underwent regioselective nucleophilic addition to the α,ß-unsaturated carbonyl moiety of ortho-benzoquinone using indole, indazole, and benzotriazole to give 4-substituted catechol derivatives in a one-pot manner. Notably, the nucleophilic substitution positions of indazole and benzotriazole were perfectly controlled. Additionally, the reaction using N-methylaniline as the nucleophile afforded a tertiary amine product.

Design, Regioselective Synthesis, and Photophysical Properties of Perfluoronaphthalene-Based Donor-Acceptor-Donor Fluorescent Dyes.

A one-step route to a series of perfluoronaphthalene-based donor (D)-acceptor (A)-D fluorescent dyes with various electron-donating groups was developed. The perfluoronaphthalene moiety in the D-A-D dyes served as a good electron-accepting aromatic ring with excellent intramolecular charge transfer properties, as determined by density functional theory calculations and measurements of the fluorescence properties in solution, in poly(methyl methacrylate) (PMMA) films, and in crystal form. Notably, replacing the naphthalene ring with perfluoronaphthalene in the D-A-D dyes carrying the phenothiazine moiety not only stabilized the highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels but also reduced the energy band gap to change the emission color from blue to yellow. Among the four synthesized perfluoronaphthalene D-A-D dyes, those bearing diphenylamino groups afforded the best fluorescence quantum yields in Et2O solution (0.60) and in PMMA film (0.65) because the propeller structure of the diphenylamino group that acts as a donor substituent effectively suppresses radiation-free deactivation. In contrast, in the crystalline state, the carbazoyl-bearing D-A-D dye provided the best fluorescence quantum yield (0.35) because the radiation-free inactivation was suppressed by π-πF stacking at the donor site, which was confirmed by single-crystal X-ray analysis.

A path integral molecular dynamics study on the NH4+ rotation in NH4+⋯XH2 (X = Be or Mg) dihydrogen bond systems.

The nuclear quantum effects (NQEs) in dihydrogen bond (DHB) complexes, i.e., NH4+⋯BeH2 and NH4+⋯MgH2, have been investigated using multicomponent quantum mechanics (MC_QM) calculations and path integral molecular dynamics (PIMD) simulation. The MC_QM method considers the NQEs, whereas PIMD considers both the NQEs and the thermal effects. The linear C3v structure is maintained in the optimized structures obtained by the static MP2 and MC_MP2 calculations, whereas the average structures obtained by the PIMD simulation are nonlinear. The strong DHB interaction in NH4+⋯MgH2 suppresses the fluctuation in the Hδ+NMg and Hδ-MgN angles, and hence, the NH4+ rotation did not occur in the simulation of NH4+⋯MgH2. The analysis of the radius of gyration revealed that the nuclear quantum fluctuation in the perpendicular direction is suppressed by the formation of the DHB complex, whereas that in the parallel direction is slightly enhanced in both the Hδ+ and Hδ- nuclei.

Effect of alkali metal cations on network rearrangement in polyisoprene ionomers.

The effects of cations, Li+, Na+, and Cs+, on the structure of ionic aggregates and network rearrangement in carboxylated polyisoprene (PI) ionomers were studied. We found that network rearrangement via interaggregate hopping of metal carboxylates is improved with a decrease in cation size, even though density functional theory (DFT) calculation indicated the increase in the attractive interaction between metal carboxylates. At the same time, we also found that as the size of the cation decreases, the inclusion of the PI segment in the ionic aggregate increases. The DFT calculation suggested the cation-π interaction between the cation and double bonds in the PI segment as the cause for the inclusion. The inclusion of the PI segment with a low glass transition temperature (Tg) plasticizes the ionic aggregate and would sterically hinder the attractive interaction between metal carboxylates. In fact, the electron spin resonance measurement revealed a decrease in the Tg of the ionic aggregate with a decrease in cation size. Based on our findings, we proposed that the inclusion of PI segments in the ionic aggregate is the possible cause for the enhancement of network rearrangement in the carboxylated PI ionomers with a decrease in the cation size.

Stabilization of Bicontinuous Cubic Phase and Its Two-Sided Nature Produced by Use of Siloxane Tails and Introduction of Molecular Nonsymmetry.

A recent intriguing finding that a helical network arrangement forms the bicontinuous cubic phase is attracting great attention for the possibility of new routes to asymmetric synthesis by achiral molecules. However, the design of the molecular structure for the cubic phase is still unrevealed. In this work, a nonsymmetric core molecule with larger naphthalene and smaller benzene moieties at each side of the central linkage and the same disiloxanyldecyloxy terminal at both terminals is shown to be the first example of molecule forming both single-layered and double-layered core assembly modes in the Ia3d phase as a single molecule system. The molecule forms the former mode at high temperatures as a thermodynamically stable phase, similarly to the symmetric naphthalene core system, whereas, on cooling below a temperature (∼350 K), a metastable Ia3d phase forms a double-layered core state down to room temperature, which is common to the benzene core system. As another effect of the nonsymmetric core, the cubic phase is maintained at room temperature for more than 100 days with slight distortion. Infrared spectral studies and quantum chemical calculations suggested the easy transformation between the two core assembly modes. The core nonsymmetry can be a versatile fine-tuning of the core assembly mode and phase stability for the cubic phase molecules.

Toward strong self-healing polyisoprene elastomers with dynamic ionic crosslinks.

To compromise high mechanical strength and efficient self-healing capability in an elastomer with dynamic crosslinks, optimization of the molecular structure is crucial in addition to the tuning of the dynamic properties of the crosslinks. Herein, we studied the effects of molecular weight, content of carboxy groups, and neutralization level of ionically crosslinked polyisoprene (PI) elastomers on their morphology, network rearrangement behavior, and self-healing and mechanical properties. In this PI elastomer, nanosized sphere-shaped ionic aggregates are formed by both neutralized and non-neutralized carboxy groups that act as stickers. The number density of the ionic aggregates that act as physical crosslinks increased with increase in the stickers' concentration, although the size of the ionic aggregates was independent of the molecular weight and the stickers' concentration. The ionic network was dynamically rearranged by the stickers' hopping between the ionic aggregates, and the rearrangement was accelerated by decreasing the neutralization level. We found that the 2Rg of the PI must be significantly larger than the average distance between the ionic aggregates to obtain a mechanically strong PI elastomer. We also found that further increase in the molecular weight is effective to enhance the dimensional stability of the elastomer. However, this approach reduced the elastomer's self-healing rate at the same time because the diffusion and randomization of the polymer chains between the damaged faces were reduced. In this work, we clearly demonstrated the principle in the optimization of the molecular structure for the ionically crosslinked PI elastomers to tune the mechanical and autonomous self-healing properties.

Alternative Route Triggering Multistep Spin Crossover with Hysteresis in an Iron(II) Family Mediated by Flexible Anion Ordering.

Multistep spin crossover (SCO) compounds have attracted much attention, since they can be great candidates for high-density multinary memory devices. The introduction of substituents, such as methyl (Me), chloro (Cl), bromo (Br), and methoxy (MeO) groups, at para positions to the phenyl-substituted tripodal N6 ligand-coordinated SCO FeII material, [FeLPh](NTf2)2 [where LPh = tris(2-{[(1-phenyl-1H-1,2,3-triazol-4-yl)methylidene]amino}ethyl)amine and NTf2 = bis(trifluoromethanesulfonyl)imide], affords a new family of solvent-free FeII complexes: [FeL4-R-Ph](NTf2)2 {where L4-R-Ph = tris[2-({[1-(4-R-phenyl)-1H-1,2,3-triazol-4-yl]methylidene}amino)ethyl]amine, where R = Me (1), Cl (2), Br (3), and MeO (4)}. 1 shows temperature invariant high-spin (HS) state, whereas the others show spin transitions with different characteristics, such as half-SCO (4), two-step SCO (3), and unusual three-step SCO with hysteresis (2). Mössbauer and X-ray absorption fine structure (XAFS) spectroscopic studies of them support the magnetic susceptibilities results. Density functional theory calculations indicate that the electronic effect of different substituents on magnetic properties is negligible in this FeII family. Single-crystal X-ray diffraction studies reveal that 1-4 has a similar packing arrangement with three-dimensional supramolecular network via intermolecular π-π and CH···π interactions between complex cations, and CH···X (X = O, N, and F) hydrogen bonding interactions between cations and inherently frustrated NTf2 anions. Variable-temperature structural studies unveil a variety of stepped SCO behaviors of 2-4 and deactivation of SCO in 1 are governed by the regulation of ordering of NTf2 counteranions through the subtle modification of terminal substituents of complex cations. Quantitative light-induced excited spin-state trapping (LIESST) effect was observed for 2-4 via green light irradiation (532 nm) at 10 K. This study opens up a new way for systematic control of magnetic response from no SCO to half-, two-step, and finally three-step SCO with hysteresis by precise tuning of the ordering of flexible NTf2 anions included in the supramolecular network with potentially SCO-active complex cations.

Synthesis and photophysical properties of selenopheno[2,3-b]quinoxaline and selenopheno[2,3-b]pyrazine heteroacenes.

In this paper, we report the novel synthesis of three different heterocycles, namely 2-arylselenopheno[2,3-b]quinoxaline, 3-(aryl/alkylselanyl)-2-arylselenopheno[2,3-b]quinoxaline and 6-phenyl-7-(arylselanyl)selenopheno[2,3-b]pyrazine derivatives, from the corresponding 2,3-dichloroquinoxaline and 2,3-dichloropyrazine derivatives. Furthermore, photophysical properties were investigated to study the effect of heteroatoms on UV-absorbance and fluorescence properties.

Molecular design of anti-spindle-like molecules by use of siloxanyl terminals for a thermotropic bicontinuous cubic phase.

Selecting 1,2-bis(aryloyl)hydrazine as a model molecular framework, this article examines how the combined modification of two molecular moieties, i.e., variation of the molecular core motif (benzene B or naphthalene N as two aromatic rings) and use of bulky and flexible siloxane segments (disiloxane Si2, trisiloxane Si3, or its branched type iSi3) at the end of both chains, affects the phase behavior including the cubic (Cub) phases such as well-known achiral Ia3d or the so-called "Im3m" phase mostly recognized as a chiral one. It was found that the use of a naphthalene core as a larger core effectively provides the compound with improved thermal stability, and the clearing temperature in the N series is ca. 50 K higher than that of the B series. On the other hand, the introduction of siloxane segments at their terminals is effective for lowering the LC-phase temperature range by several tens of K. Focusing on the Cub phases, only the introduction of the disiloxane Si2 segment was useful for their formation, and we envisioned how much degree the anti-spindle shape of the average molecular shape is in the Ia3d phase. The use of the trisiloxane Si3/iSi3 segment primarily led to the formation of columnar (Col) phases. Consideration of the chemical composition revealed that the delicate balance between the three molecular moieties, siloxane terminal, alkyl spacer, and aromatic core part, is critical for the Cub phase formation, and it can be summarized as the threshold weight fraction of the alkyl spacer in the three moieties being 0.284 or larger, which derives an anti-spindle shape favorable for the formation of the Ia3d-Cub phase.

Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein.

Quinoxaline is one of the privileged heterocyclic fragments for drug molecules. Quinoxaline anticancer drug candidates XK469 and CQS exhibit antiproliferative and proapoptotic properties against various cancers. Based on their chemical structures, we therefore synthesized a series of quinoxaline-1,3,4-oxadiazole hybrids and assessed their anticancer potential on human leukemia HL-60 cells. Although these hybrids exerted significant inhibition of HL-60 cell proliferation, they showed high cytotoxicity on human normal cells (WI-38). Utilizing information from molecular modelling of the hybrids to the anti-apoptotic Bcl-2 protein, we added substructures including phenyl, piperazine, piperidine, and morpholine rings to their frameworks. The designed quinoxaline-1,3,4-oxadiazole hybrid derivatives successfully induced apoptotic response on HL-60 cells with low toxicity on WI-38 cells. Furthermore, RT-PCR analysis demonstrated that these derivatives predominantly inhibit Bcl-2 expression. Our findings highlight the great potential for the development of synthetic quinoxaline-1,3,4-oxadiazole hybrid derivatives as proapoptotic anticancer agents.

Synthesis of carbazoloquinone derivatives and their antileukemic activity via modulating cellular reactive oxygen species.

Carbazoloquinone alkaloids are of great interest as privileged structures for anticancer drug molecules. The purpose of this study was to investigate the structure-activity relationships of carbazoloquinone derivatives as anticancer agents. A series of carbazoloquinones including murrayaquinone A, koeniginequinones A and B, and related analogues were therefore prepared. Palladium-catalyzed intramolecular cyclization reaction mechanism was well elucidated by DFT calculations. Treatment of the synthesized derivatives showed cytotoxicity on human leukemia HL-60 cells in a dose-dependent fashion. In addition, murrayaquinone A and ß-brazanquinone elevated cellular levels of reactive oxygen species (ROS), thereby triggering apoptosis. Our findings emphasize the excellent potential of carbazoloquinone derivatives as ROS-inducing anticancer agents.

Selenolactams as Synthetic Intermediates for the Synthesis of Polycyclic Amines via Seleno-Claisen Rearrangements.

A highly diastereoselective α-allylation of selenolactams with allyl halides is reported. DFT analyses and experimental observations suggested that this reaction proceeds via a Se-allylation of the eneselenolates of the lactams followed by a seleno-Claisen rearrangement. The thus-obtained products could be efficiently transformed into polycyclic amines using a previously developed sequential addition of organometallic reagents and ring-closing metathesis.

Synthesis of thieno[2,3-b]quinoline and selenopheno[2,3-b]quinoline derivatives via iodocyclization reaction and a DFT mechanistic study.

In this letter, we report the regioselective iodocyclization reaction of 3-alkynyl-2-(methylthio)quinolines and 3-alkynyl-2-(methylseleno)quinolines for the synthesis of thieno[2,3-b]quinoline and selenopheno[2,3-b]quinoline derivatives. Furthermore, by employing various palladium-catalyzed Sonogashira, Suzuki, and Heck reactions, the structural diversification of the resulting halide derivatives, which can act as the important intermediates for building other valuable compounds, was achieved. All compounds were fully characterized by the FT-IR, mass, 1H NMR, and 13C NMR spectral data. Finally, the structure of the thieno[2,3-b]quinoline derivative was confirmed by X-ray crystallography. This methodology provided a novel pathway to access quinoline fused heterocycles via iodocyclization reaction. Furthermore, the reaction process was well elucidated by density functional theory calculations.

Systematic exploitation of thermotropic bicontinuous cubic phase families from 1,2-bis(aryloyl)hydrazine-based molecules.

Rational design of molecules that exhibit a thermotropic bicontinuous cubic (Cub) phase has been earnestly desired. In this work, we describe the suitable selection of a molecular motif that has enabled the systematic exploitation of eight new series of Cub-phase molecules with symmetric molecular cores, N-n (1), PB-n (2), S-n (3), and PEB-n (4), and unsymmetric cores, B-N-n (5), B-PB-n (6), B-S-n (7), and B-PEB-n (8). These eight series all originate from achiral chain-core-chain type rod-like molecules that exhibit two types of Cub phases, an achiral Ia3d phase, and a chiral phase. All the Ia3d phases formed were found to be isomorphous structures, with their cell dimensions being proportional to the core size, and the same was true for the latter chiral phase. We demonstrated that the formation is mainly governed by the segregation between core and alkyl moieties of the molecules, and thus, by the weight fraction of the core portion fcore. This work also demonstrates that the central dicarbonylhydrazine linkage bearing intermolecular hydrogen bonding ability exhibits a pinning effect that prevents slippage of π-stacks of molecules, which is critical for the formation of the two Cub phases that are composed of chiral networks with twisted molecular arrangements. In each series, the emergence of spontaneous chirality formation that occurred in the chiral phase was limited to between 0.36 and 0.50 in the range of fcore. An interesting insight was that the introduced unsymmetry of the molecular core strongly influenced the phase behavior, which lowered the temperature range of Cub phases to around that of the smallest core series B-n, while the high temperature limit (Tc) was roughly proportional to the core size, as determined by the strength of intermolecular π-π interactions.

The Origin of High Stereoselectivity in Di-tert-butylsilylene-Directed α-Galactosylation.

The origin of the high α(1,2-cis)-stereoselectivity in the reaction of galactosyl and galactosaminyl donors with a di-tert-butylsilylene (DTBS) group with several nucleophiles has been elucidated by means of experimental and computational approaches. DTBS overcomes any other cyclic protecting groups examined to date and the ß(1,2-trans)-directing effect due to the neighboring participation by CO groups at C2. Requirements for the α(1,2-cis)-stereoselectivity are as follows: (1) generation of an oxocarbenium ion; (2) a galacto-type glycosyl donor with a cyclic protecting group bridging O4 and O6 to form a six-membered ring; (3) through-space electron donation from O4 and O6 into the empty p-orbital of the anomeric carbon to stabilize the oxocarbenium intermediate; (4) steric hindrance due to bulky alkyl substituents on the cyclic protecting group to prevent nucleophilic attack from the ß-face; and (5) a 4,6-O-silylene structure. Furthermore, it was found that the strong stereodirecting effect of the DTBS group was unique and specific among the various cyclic protecting groups examined.

Nuclear quantum effect and H/D isotope effect on F + (H2O)n → FH + (H2O)n-1OH (n = 1-3) reactions.

Potential energy profiles for F + (H2O)n → FH + (H2O)n-1OH (n = 1-3) reactions, which are widely relevant to solvent effects on chemical reactions, have been investigated using the conventional quantum mechanical (QM) methods and our multicomponent QM (MC_QM) methods, which can take account of nuclear quantum effect of light nucleus, such as proton and deuteron. For these reactions, Li and co-workers [G. Li et al., J. Phys. Chem. A 117, 11979 (2013)] reported that (i) for F + H2O → FH + OH reaction, MPW1K density functional gave the best barrier among 49 kinds of density functionals and (ii) the energy of transition state of F + (H2O)2 → FH + (H2O)OH reaction is lower than that of the separated reactant molecules by the contribution of the second water molecule using high-accuracy CCSD(T)/cc-pVQZ calculations. We have found that ω B97XD density functional reasonably reproduces the CCSD(T) geometries well, whereas MPW1K was not suited for analyzing F + (H2O)2 → FH + (H2O)OH reaction. Our MC_QM calculations reveal that nuclear quantum nature of hydrogen nucleus lowers the activation barrier of the reactions. The H/D isotope effect on F + (H2O)n → FH + (H2O)n-1OH (n = 1-3) reactions was also investigated.