Biased Bowl-Direction of Monofluorosumanene in the Solid State

Yakiyama Y., Li M., Zhou D., et al. Biased Bowl-Direction of Monofluorosumanene in the Solid State. Journal of the American Chemical Society 146, 5224 (2024); https://doi.org/10.1021/jacs.3c11311.A new curved π-conjugated molecule 1-fluorosumanene (1) was designed and synthesized that possesses one fluorine atom on the benzylic carbon of sumanene. This compound can exhibit bowl inversion in solution, leading to the formation of two diastereomers, 1endo and 1exo, with different dipole moments. Experimental and theoretical investigation revealed an energetical relationship among 1exo, 1endo, and solvent to realize the various endo:exo ratios in the single crystals of 1 depending on the crystallization solvent. Significantly, the molecular dynamics (MD) simulations revealed that 1exo positively worked for the elongation of the stacking structure and the final endo:exo ratio was affected by the relative stability difference between 1endo and 1exo derived by solvation. Such an arrangeable endo:exo ratio of 1 realized the preparation of unique materials showing a different dielectric response from the same molecule 1 just by changing the crystallization solvent

Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy

Dielectric Response of 1,1-Difluorosumanene Caused by an In-Plane Motion

We have designed and synthesized a new curved π-conjugated molecule, 1,1-difluorosumanene (1), which possesses two fluorine atoms on the same benzylic carbon of unsubstituted sumanene, producing a large dipole moment along the in-plane direction. Thermal analyses, variable-temperature X-ray diffraction, and IR measurements indicated a 120° in-plane motion of 1 in the stacking columns, which did not cause any phase transition in the crystalline state. Indeed, dielectric measurements on powder and single-crystal forms of 1 showed that both the real (ε1) and imaginary (ε2) parts of the dielectric constant were enhanced above ~360 K at 1 MHz with a Debye-type dielectric relaxation, confirming that 1 underwent a pendulum fluctuation induced by the external electric field

Bowl-Direction Control of Monofluorosumanene in the Solid State

A new curved π-conjugated molecule-1-fluorosumanene (1) was designed and synthesized which possesses one fluorine atom on the benzylic carbon of sumanene. This compound is able to exhibit bowl inversion in solution, leading to the formation of two diastere-omers 1endo and 1exo with different dipole moment. Experimental and theoretical investigation revealed energetical relationship among 1exo, 1endo and solvent to realize the control of exo:endo ratio in the single crystals of 1 by the correct choice of the crystalliza-tion solvent. Significantly, the molecular dynamics (MD) simulations revealed that 1exo positively worked for elongation of the stacking structure and the final exo:endo ratio was affected by the relative stability difference between 1endo and 1exo derived by solv-ation. Such controllable exo:endo ratio of 1 realized the preparation of unique materials showing totally different dielectric response from the same molecule 1 just by changing crystallization solvent

Carrier Transport Switching of Ferroelectric BTBT Derivative

Alkylamide-substituted [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivative of BTBT-NHCOC14H29 (1), which has ferroelectric N–H···O= hydrogen-bonding network of alkylamide group and two-dimensional (2D) electric structure of BTBT π-cores, was prepared to design the external electric field-responsive organic semiconductors. The short-chain derivative of BTBT-NHCOC3H7 (1’) revealed the coexistence of a 2D electronic band structure based on the herringbone BTBT arrangement and the one-dimensional (1D) hydrogen-bonding chain. 1 formed a smectic E (SmE) liquid crystal phase above 412 K and showed ferroelectric hysteresis in the electric field–polarization (P–E) curves at 403–433 K. The remanent polarization (Pr) and coercive electric field (Ec) of 1 at 408 K, 0.1 Hz were 24.0 μC cm–2 and 5.54 V μm–1, respectively. By thermal annealing of thin-film 1 at 443 K, the molecular assembly structure of 1 changed from a monolayer to a bilayer structure with high crystallinity, resulting in conducting layers of BTBT parallel to the substrate surface. The organic field-effect transistor (OFET) device with thermally annealed thin-film 1 showed p-type semiconducting behavior with the hole mobility of 1.0 × 10–3 cm2 V–1 s–1. Furthermore, device 1 showed switching behavior of semiconducting properties by electric field poling and thermal annealing cycle. The electric field response of ferroelectrics modulated the molecular orientation and conduction properties of organic semiconductors, resulting in external electric field control of carrier transport properties

Isobutyric acid enhances the anti-tumour effect of anti-PD-1 antibody

Abstract The low response rate of immune checkpoint inhibitors (ICIs) is a challenge. The efficacy of ICIs is influenced by the tumour microenvironment, which is controlled by the gut microbiota. In particular, intestinal bacteria and their metabolites, such as short chain fatty acids (SCFAs), are important regulators of cancer immunity; however, our knowledge on the effects of individual SCFAs remains limited. Here, we show that isobutyric acid has the strongest effect among SCFAs on both immune activity and tumour growth. In vitro, cancer cell numbers were suppressed by approximately 75% in humans and mice compared with those in controls. Oral administration of isobutyric acid to carcinoma-bearing mice enhanced the effect of anti-PD-1 immunotherapy, reducing tumour volume by approximately 80% and 60% compared with those in the control group and anti-PD-1 antibody alone group, respectively. Taken together, these findings may support the development of novel cancer therapies that can improve the response rate to ICIs

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography–Guided Emergency Percutaneous Coronary Intervention

Background The prognostic impact of optical coherence tomography–diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real‐world settings. Methods and Results This investigator‐initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography–guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia‐driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography–guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One‐year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log‐rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log‐rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log‐rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1‐year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35–14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05–4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause‐based optical coherence tomography–guided optimization