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Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. At initial diagnosis, approximately 20% of patients are diagnosed with metastatic CRC (mCRC). Although the APC‒Asef interaction is a well-established target for mCRC therapy, the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor. In this study, we identified a novel structural scaffold based on MAI inhibitors, the first-in-class APC‒Asef inhibitors we reported previously. ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed, and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound. In addition, the cocrystal structure validated that the two-layer π‒π stacking interactions were essential for inhibitor stabilization in the bound state. Furthermore, in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC‒Asef interaction. These results provide an intrinsic structural basis to further explore drug-like molecules for APC‒Asef-mediated CRC therapy. This study elucidated an ONIOM model-driven design and optimization of inhibitors targeting APC‒Asef based on the unique "Sandwich" π‒π interactions. [Display omitted] [ABSTRACT FROM AUTHOR]

We have investigated the ability of para-X-phenylboronic acid (para-X-ba) to enable reactivity of trans-1,2-bis(4-pyridyl)ethylene (bpe) to direct intermolecular [2 + 2] photodimerization via computational chemistry. Para-X-ba would support the formation of discrete four component hydrogen bonded molecular assemblies wherein π-π stacking of a pyridyl-functionalized alkene would conform to undergo [2 + 2] photodimerization. We have demonstrated by computational 1H NMR data the effect of electron-withdrawing and donating substituents in (para-X-ba):::(bpe)||(bpe):::(para-X-ba) complexes to assemble bpe into π-π stacking via –(B)O − H···N– hydrogen bonds to react to afford (para-X-ba):::tpcb:::(para-X-ba) complexes (X = NO2, CN, F, Cl, Br, C(O)CH 3 , OCH 3 , OH, NH 2 and H where || and ∙∙∙ denote π-π stacking and hydrogen bonds). Also, these interactions have been investigated at M05-2X/6-311++G** level of theory in detail in terms of the energetic, geometrical parameters and electron density properties to characterize and to examine the strengthening of the interactions. There are good relationships between the NMR, AIM, energy data and Hammett constants. [ABSTRACT FROM AUTHOR]

Highlights • Graphene/Fe 3 O 4 nanocomposite used for effective removal of ten triazole fungicides. • Kinetics and thermodynamics study to investigate the adsorption process in nature. • Experimental and molecular docking study to discuss the interactions in adsorption. • π-π stacking was the dominant role in adsorption of triazole fungicides on graphene. Abstract In this study, graphene/Fe 3 O 4 was prepared and utilized as a adsorbent for removal of ten commonly used triazole fungicides in agriculture, namely tebuconazole, hexaconazole, flutriafol, triadimenol, triazolone, epoxiconazole, penconazole, myclobutanil, paclobutrazol and metconazole in aqueous solution. The removal efficiency for ten fungicides (20 µg/mL) ranged from 85.2% to 96.0% by adding 20 mg of graphene/Fe 3 O 4 into 50 mL water solution. Factors might affect the adsorption capacity, such as contact time, adsorbent amount, solution pH and ionic strength were investigated. The study on adsorption kinetics and thermodynamics were done by taking tebuconazole as an example. Kinetics data followed the pseudo second-order model and adsorption equilibrium conformed to the Langmuir isotherm model. Thermodynamics data revealed that the adsorption was a spontaneous physisorption process in nature. Further, combining the experimental results with molecular docking study, the possible interactions in the adsorption, such as electrostatic interaction, hydrogen bonding interaction, π-π stacking, hydrophobic interaction and cation-π interaction were discussed, and π-π stacking seemed to be the dominant factor, which provided a new insight for understanding how the adsorbates interact with graphene. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

In this work, with a general interest to understand the charge transport properties of mono substituted pyrene molecules which can be used as multifunctional materials in Organic Light Emitting Diodes (OLED), we have analyzed the charge transport properties calculated from DFT methods for a number of the mono substituted pyrene molecules whose crystal structures have been obtained from Cambridge structural data base (CSD). The data for the analysis was obtained by optimizing the geometries of the molecules in gas phase and subsequently generating the frontier orbitals and calculation of reorganization energies; transfer integrals in the solid state for various path ways were also calculated. The drift mobilities were then estimated from this data. The reasons for the variation of the drift mobilities in this group are then analyzed and the pattern reported. This work would be useful for generating new efficient pyrene derivatives and for improving existing ones for use in OLED. [ABSTRACT FROM AUTHOR]

The Ni(II) complex of dimethylglyoxime (dmgH where H is dissociable oxime proton) occurs as an infinite chain of the discrete molecule Ni(dmgH) 2 with a Ni Ni distance of 3.24 Å. Density Functional Theoretical calculations, using LanL2DZ and 6-31+G(2d,p) as two sets of basis functions and M06-2X as the functional, show that the dimeric unit [Ni(dmgH) 2 ] 2 has a cohesive energy more than 20 kcal mol −1 . This energy is almost same in the corresponding hypothetical zinc analogue. Since there cannot be any metal-metal bond in [Zn(dmgH) 2 ] 2 , possibility of a Ni Ni bond in [Ni(dmgH) 2 ] 2 is precluded. This is supported by qualitative m.o. analyses also. Further the Ni Ni bond distance is almost same as the sum of the van der Waals radii of the two Ni atoms as designated by Bondi which is 3.26 Å. It is found that the binding energy in [Ni(dmgH) 2 ] 2 arises from aromatic-aromatic interactions and that in [Zn(dmgH) 2 ] 2 due to π-π interactions between the ligand frameworks. An energy decomposition analysis show that electrostatic and dispersion effects govern the cohesive energy in [Ni(dmgH) 2 ] 2 and [Zn(dmgH) 2 ] 2 . Their numerical values are comparable. The orbital interactions in them are relatively less. [Zn(dmgH) 2 ] n is not stable for n > 2. There are two types of chelate rings in Ni(dmgH) 2 monomer – a five membered one with six π electrons and a six membered one having ten σ electrons. Consequently the smaller chelate ring is π-aromatic and the other one σ-aromatic. Such a conclusion is drawn from considerably negative values of NICS(0) (Nucleus Independent Chemical Shift at the centroid of a ring) for the two chelates. The corresponding chelates in [Zn(dmgH) 2 ] 2 are not aromatic. [ABSTRACT FROM AUTHOR]

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[Display omitted] • The cooperativity between π–π stacking and ion–π interactions mainly depend on the nature of aromatic ring. • The reinforcement of π–π stacking and ion–π interactions is confirmed in the cation–BEN–TAZ and anion–HFB–TAZ triads. • Unlike cation–π interactions, π–π stacking and anion–π interactions reinforce each other in ion–TAZ–HFB ternary complexes. • This behavior is reversed in the ion–TAZ–BEN triads. • Compared to ion–π interactions, the π–π stacking is mostly affected by simultaneous presence of both interactions. In this manuscript, the role of nature of aromatic ring on cooperativity between π–π stacking and ion–π interactions is investigated in the cation–benzene–s-triazine, anion–hexafluorobenzene–s-triazine, ion–s-triazine–benzene and ion–s-triazine–hexafluorobenzene complexes at M06-2X/6–311++G(d,p) level of theory. The reinforcement of π–π stacking and ion–π interactions is confirmed in the cation–benzene–s-triazine and anion–hexafluorobenzene–s-triazine ternary complexes where both interactions exist concurrently. It is found that π–π stacking and cation–π interactions reinforce each other in the ion–s-triazine–benzene triads while an opposite trend is obtained in the presence of anion–π interactions. On the other hand, contrary to cation–π interactions, π–π stacking and anion–π interactions are strengthened in the ion–s-triazine–hexafluorobenzene triads where both interactions coexist. These results indicate that the cooperative and synergistic effects between π–π stacking and ion–π interactions mainly depend on the nature of aromatic ring. Compared to ion–π interactions, it is also found that the π–π stacking is mostly affected by simultaneous presence of both interactions. [ABSTRACT FROM AUTHOR]

Thermosetting epoxy resins containing polyaromatic backbones such as naphthalene and dihydroanthracene showed low coefficients of thermal expansion (CTE) and high glass transition temperatures. 4,4′-Diaminodiphenyl sulfone (DDS)-cured polyaromatic epoxy resin showed a CTE of 49.8 ppm/K with a Tg of 235°C. These values are 15.3 ppm/K lower and 19°C higher than those of DDS-cured bisphenol A type epoxy resin (DGEBA), and 22.0 ppm/K lower and 77°C higher than those of cresol novolac(CN)-cured DGEBA. There is a correlation between density and CTE of the cured resins, some contribution of the π-π stacking effect for polyaromatic backbones of epoxy resins and the stereostructure of DDS to decrease in CTE was indicated. Moreover, boron trifluoride monoethylamine complex (BTMEA) was found to be effective as a curing accelerator for DDS-cured epoxy resins. [ABSTRACT FROM AUTHOR]

• Fluorination impact on intermolecular coupling was studied. • Fluorine substitution significantly modified the molecular charge distribution. • Fluorination increased the dipole moment and decreased exciton binding energy. • Asymmetric fluorine substitution showed higher transfer integral. A detail study was performed to get deeper understanding of fluorination impact on intermolecular coupling and intermolecular interactions. Results showed that fluorine substitution plays an important role to modify the charge distribution or electrostatic potential as well non-covalent interaction between molecules. Dipole moment difference between ground and first excited states has increased while exciton binding energy has decreased by increasing the fluorine atoms. SM3 with asymmetric fluorine substitution showed higher transfer integral due to stronger attractive interactions. By proper substitution of fluorine atom, π-π stacking distance can be reduced to achieve higher electronic coupling. Substitution of fluorine atoms has increased the reorganization energy and non-linear optical response. [ABSTRACT FROM AUTHOR]