A tetramesityl derivative of hitherto unknown tetracyclopentadef,jkl,pqr,vwxtetraphenylene (TCPTP), which is a potential tetraradicaloid hydrocarbon, was synthesized. Theoretical calculations based ...on spin‐flip time‐dependent density functional theory predict that the closed‐shell D2h form of TCPTP is more stable than the open‐shell D4h form with its slightly tetraradical character. The tetramesityl derivative (Mes)4‐TCPTP exhibits remarkable antiaromaticity as a result of the peripheral 20‐π‐electron circuit, which causes an absorption maximum at a long wavelength and a small HOMO–LUMO gap. In solution, (Mes)4‐TCPTP most likely adopts rapidly equilibrating D2h structures that interconvert via the D4h transition state. X‐ray crystallographic analysis showed (Mes)4‐TCPTP as an approximate D2h structure.
Aromatic? A tetramesityl derivative of hitherto unknown tetracyclopentadef,jkl,pqr,vwxtetraphenylene, a potential tetraradicaloid hydrocarbon, was synthesized. It exhibits remarkable antiaromaticity as a result of the peripheral 20‐π‐electron circuit. In solution, it adopts closed‐shell D2h structures that rapidly equilibrate via the D4h structure, and in crystals, it adopts an approximate D2h structure.
The consequence of unpaired electrons in organic molecules has fascinated and confounded chemists for over a century. The study of open-shell molecules has been rekindled in recent years as new ...synthetic methods, improved spectroscopic techniques and powerful computational tools have been brought to bear on this field. Nonetheless, it is the intrinsic instability of the biradical species that limits the practicality of this research. Here we report the synthesis and characterization of a molecule based on the diindenob,ianthracene framework that exhibits pronounced open-shell character yet possesses remarkable stability. The synthetic route is rapid, efficient and possible on the gram scale. The molecular structure was confirmed through single-crystal X-ray diffraction. From variable-temperature Raman spectroscopy and magnetic susceptibility measurements a thermally accessible triplet excited state was found. Organic field-effect transistor device data show an ambipolar performance with balanced electron and hole mobilities. Our results demonstrate the rational design and synthesis of an air- and temperature-stable biradical compound.
Using spin-unrestricted density functional theory, the longitudinal static second hyperpolarizability γ has been investigated for an asymmetric azulene-like open-shell condensed-ring molecule (1) as ...well as for its symmetric almost closed-shell and open-shell analogues (pentacene (2) and its dicyclopenta- (3) and dicyclohepta-fused (4) analogues). It is found that the symmetric systems, 3 and 4, having intermediate diradical characters show a 6–9 times enhancement of γ as compared to 2, but that this enhancement is even larger (by a factor of 30) for the asymmetric diradicaloid, 1. Geometrical, electronic, and magnetic descriptors have shown that in 1 the terminal seven- and five-membered rings display a cooperative push–pull effect, leading to a large dipole moment, that seems to reinforce its aromaticity as well as its ionic character, whereas 3 and 4 are mostly neutral diradicaloids and are less aromatic. These features have been rationalized by resorting to an asymmetric two-site model within the valence configuration interaction method. It is found that the diradical character decreases with increasing the asymmetricity and the exchange interaction. Then, an increase in the exchange interaction leads to a decrease of the asymmetricity value defining the critical point (where the diradical and ionic contributions of the ground and first excited states exchange) and increases the amplitudes of the γ extrema. The increase in asymmetricity has been realized in two ways: (i) by applying a static electric field to the symmetric nonalternant condensed-ring diradicaloid (3), and (ii) by designing an asymmetric nonalternant azulene-like condensed-ring conjugated system (1). Scheme ii gives a triplet ground state and it therefore requires large r K , i.e., small HOMO–LUMO overlap. As a result, such an increase of r K in scheme ii leads to a new class of asymmetric NLO systems, having a ferromagnetic ground state and a singlet first excited state. The latter has an intermediate or small diradical character y and it exhibits negative γ values with amplitudes larger than those of symmetric diradicaloids with smaller r K .
Carbon atoms have the potential to produce a variety of fascinating all-carbon structures with amazing electronic and mechanical properties. Over the last few decades, several efforts have been made ...using experimental and computational techniques to functionalize graphene, carbon nanotubes and fullerenes for potential use in modern hi-tech electronic, medicinal, optical and nonlinear optical (NLO) applications. Since photons replaced electrons as a carrier of information, the field of NLO material design has drawn immense interest in contemporary materials science. There have been several reports of bridging the gap between the exciting fields of carbon nanomaterials and NLO materials by functionalizing carbon nanomaterials for potential NLO applications. In contrast to previous reports of the design of third-order NLO materials using conventional closed-shell materials, a novel strategy using open-shell diradical molecular systems has recently been proposed. Quantum chemically, diradical character is explained in terms of the instability of the chemical bonds in open-shell molecular systems. Interestingly, several carbon nanomaterials, which naturally possess open-shell singlet configurations, have recently gained momentum in the design of these classes of open-shell NLO materials with excellent NLO properties, stability and diversity. The present review establishes a systematic sequence of different studies (spanning over two decades of intense research efforts), starting from the simplest theoretical two-site diradical model, continuing to its experimental and theoretical realization in actual chemical systems, and finally applying the abovementioned model/rule to novel carbon nanomaterials to tune their NLO properties, particularly their second hyperpolarizability (γ). In the present report, we highlight several recent efforts to functionalize carbon nanomaterials by exploiting their open-shell diradical character to achieve efficient third-order NLO properties. Several issues and opportunities are discussed, including the inherited disadvantages of both experimental (the high reactivity and short life of diradical compounds) and quantum (need for multi-reference methodology) techniques when dealing with carbon nanomaterials. A comparative analysis of several quantum chemical investigations, along with contemporary experimental results, will be performed to emphasize the core issues and opportunities related to carbon nanomaterials with singlet open-shell diradical character. Thus, the present review will highlight carbon nanomaterials with diradical/biradical character for their prospective applications in the NLO field.
Focusing on the original and extended indenofluorene frameworks, we theoretically investigate the interplay between the open-shell character, the aromaticity, and the second hyperpolarizabilities γ. ...Interestingly, the odd-electron density distribution, which illustrates the spatial contribution of the open-shell character, is found to well correlate with the magnetic shielding tensor distribution, which indicates the magnetic criteria of the aromaticity. This can be explained with the partial destruction of the π-delocalization due to the emergence of odd (unpaired) electrons. Further investigation on the γ values, which are third-order nonlinear optical (NLO) properties at the molecular scale, reveals the correlation of strong enhancement of γ and its density distribution to the intermediate open-shell character and its odd-electron density distribution. These results will contribute not only to the detailed understanding of the structure–NLO property relationships in the indenofluorene frameworks but also to building new design guidelines for highly efficient NLO molecules based on the open-shell character–aromaticity correlation.
The impact of intermolecular interactions on the third‐order nonlinear optical (NLO) properties of open‐shell molecular aggregates has been elucidated by considering one‐dimensional aggregates of π–π ...stacked phenalenyl radicals with different intermolecular distances and the long‐range corrected spin‐unrestricted density functional theory method. In the phenalenyl dimer, which can be considered as a diradicaloid system, the diradical character strongly depends on the intermolecular distance, and the larger the intermolecular distance is, the larger the diradical character becomes. Then, around the equilibrium stacking distance that corresponds to an intermediate diradical character, its second hyperpolarizability (γ) is maximized and its value per monomer exhibits about a 30‐fold enhancement with respect to the isolated phenalenyl monomer. This suggests that equilibrium is an optimal compromise between localization and delocalization of the radical electron pairs in such pancake bonding. No such effect was observed for the closed‐shell coronene dimer. Moreover, when going from the dimer (diradical) to the tetramer (tetraradical), the γ‐enhancement ratio increases nonlinearly with the aggregate size, whereas switching from the singlet to the highest spin (quintet) state causes a significant reduction of γ. Finally, for the tetramer, another one‐order enhancement of γ is achieved for the dicationic singlet relative to its singlet neutral state. These results demonstrate the key role of intermolecular π–π stacking interactions and charge in open‐shell (supra)molecular systems to achieve enhanced third‐order NLO properties.
Close encounters of the third order: The impact of intermolecular interactions on the third‐order nonlinear optical (NLO) properties of one‐dimensional open‐shell molecular aggregates composed of phenalenyl radicals is theoretically investigated (see figure).
Immune checkpoint inhibitors have shed light on the importance of antitumor immunity as a therapeutic strategy for hepatocellular carcinoma (HCC). The altered glucose metabolism known as the Warburg ...effect recently has gained attention as a cancer immune-resistance mechanism. Considering glycolysis inhibitors as therapeutic agents, their specific delivery to cancer cells is critical not to induce adverse effects. Thus, we investigated antitumor effects of a glycolysis inhibitor, consisting of 2-deoxy-D-glucose (2DG)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (2DG-PLGA-NPs), against hepatocellular carcinoma in mice.
The antitumor effects of 2DG-PLGA-NPs were examined using hepatoma cell lines, xenograft tumors, and hepatocarcinogenic and syngeneic mouse models.
The 2DG-PLGA-NPs induced cytotoxic effects and antitumor immunity through enhanced T-cell trafficking. In addition, 2DG-PLGA-NPs induced decreased lactate production and increased interferon-γ–positive T cells in liver tumors. Human CD8+ T cells cocultured with 2DG-PLGA-NP–treated Huh7 cells showed their increased interferon-γ production and glucose uptake compared with the CD8+ T cells co-cultured with PLGA-NP–treated Huh7 cells. Chemotaxis of CD8+ T cells was suppressed by lactate and enhanced by glucose. Interferon-γ enhanced CD8+ T-cell chemotaxis in both an autocrine and paracrine manner. Notably, the 2DG-PLGA-NPs augmented chemokine (CXCL9/CXCL10) production in liver tumors via interferon-γ–Janus kinase–signal transducers and activator of transcription pathway and 5' adenosine monophosphate-activated protein kinase–mediated suppression of histone H3 lysine 27 trimethylation. These 2DG-PLGA-NPs not only amplified antitumor effects induced by sorafenib or an anti–programmed death-1 antibody, but also suppressed anti–programmed death-1–resistant tumors.
The newly developed 2DG-PLGA-NPs showed antitumor immunity and cytotoxicity in liver tumors in mice, suggesting the potential of 2DG-PLGA-NPs for future clinical applications.
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The reduced and oxidized states of an open-shell diindenob,ianthracene (DIAn) derivative have been investigated by experimental and theoretical techniques. As a result of moderate biradical ...character and the ability of cyclopenta-fused scaffolds to stabilize both positive and negative charges, DIAn exhibits rich redox chemistry with four observable and isolable charged states. Structural and electronic properties of the DIAn system are brought to light by UV–vis–NIR and Raman spectroelectrochemical measurements. Aromatization of the diindeno-fused anthracene core upon successive single-electron injections is revealed through single-crystal X-ray diffraction of radical anion and dianion salts. We present a rare case where the pseudoaromatic/quinoidal ground state of a neutral biradical polycyclic hydrocarbon leads to a stable cascade of five redox states. Our detailed investigation of the transformation of molecular structure along all four redox events provides a clearer understanding of the nature of charge carriers in ambipolar organic field-effect transistors.
By using spin‐unrestricted density functional theory methods, the relationship between the diradical character y and the second hyperpolarizability γ (the third‐order nonlinear optical (NLO) ...properties at the molecular scale) for four‐membered‐ring diradical compounds, that is, cyclobutane‐1,3‐diyl, Niecke‐type diradicals, and Bertrand‐type diradicals, were investigated by focusing on the substitution effects of heavy main‐group elements as well as of donor/acceptor groups on the y and γ values. It has been found that i) γ is enhanced in the intermediate y region for these four‐membered‐ring diradicals, ii) Niecke‐type diradicals with intermediate y values, which are realized by tuning the combination of the main‐group elements involved, exhibit larger γ values than Bertrand‐type diradicals, and iii) the y value and thus γ value can be controlled by modifying the both‐end donor/acceptor substituents attached to carbon atoms in Nicke‐type C2P2 diradicals. These results demonstrate that four‐membered‐ring diradicals involving heavy main‐group elements exhibit high controllability of the y and γ, which indicates the potential applications of four‐membered‐ring diradicals as a building block of highly efficient open‐shell NLO materials.
Relationship issues: The relationship between the diradical character (y) and second hyperpolarizability (γ; third‐order nonlinear optical property) for several four‐membered‐ring diradicals involving heavy main‐group elements was investigated (see figure). It is found that γ is enhanced in the intermediate y region, and that y and γ can be controlled by modifying the main‐group elements and the donor/acceptor groups substituted into the four‐membered ring.
The long-range corrected spin-unrestricted density functional theory, LC-UBLYP, method has been employed to unravel the relationship between the hole (referred to as “antidot”) structure of hexagonal ...graphene nanoflakes (HGNFs) and their properties, including their multiradical characters y i the occupation number of the lowest unoccupied natural orbital (LUNO)+i (i = 0, 1, ...), aromaticity, and the second hyperpolarizabilities (γ), which is the third-order nonlinear optical (NLO) response at the molecular level. These systems exhibit a wide range of open-shell/multiradical character, which shows an oscillatory behavior as a function of increasing the size of the antidot. This structural dependence is shown to originate from the oscillatory variations in the HOMO–LUMO energy gap, which result from the fact that the bonding and antibonding interactions between the central antidot-shape HGNFs and the surroundings alternate in both the HOMO and the LUMO as going from the center of the molecule to the peripheral region. Moreover, the multiradical character of these structures is strongly correlated with the variations of magnetic criteria of aromaticity, the nucleus-independent chemical shift (NICS) and the out-of-plane diagonal component of the magnetic shielding tensor (−σ zz ), as well as with the γ. So, systems with larger multiradical characters tend to exhibit larger NICS and −σ zz values, i.e., less aromaticity. Although the number of π electrons of the antidot HGNFs is smaller than that of the corresponding perfect C150H30 HGNF, their γ value can be larger as evidenced by the antidot C126H42 HGNF, which has intermediate multiradical characters (y 0 = y 1 = 0.658) and displays a γ value 1.7 times larger than that of the perfect HGNF. These strong impacts of the antidot structure on the third-order NLO properties indicate that the antidot HGNFs are promising building blocks for a new class of multiradical NLO materials, the properties of which can be controlled by adjusting the antidot size.