Singlet-triplet energy gaps modulation of Diindeno [1,2-b: 1’2’-g] anthracene molecular family

Nowadays there is a large interest in organic materials based on diradical polycyclic aromatic hydrocarbons (PAHs) due to their unique properties, such as narrow frontier-orbital energy gaps, strong absorption in the visible spectrum, etc. However, the inherent diradical nature make these compounds with limited chemical stability giving rise to rapid decomposition under ambient conditions thus reducing their practical use. In recent years PAH diradicals that exhibit remarkable stability have been prepared thanks to the description of efficient synthetic routes to access them. One of these remarkable cases is the diindeno [1,2-b: 1’2’-g] anthracene, named as DIAn. DIAn is constituted by antiaromatic segments together with a central pro-aromatic structure. One of the important observable properties of diradicals is the singlet-triplet energy gap, ∆EST, which is intimately connected with the diradical character. The possibility of access to the molecular structure of diradicals is very valuable since properties such as the bond-order or the bond-length alternation of the mentioned moieties reveal the diradical content. Electronic and vibrational spectroscopies are alternative sources of structural information that often compensate the absence of solid-state structures. In this communication, we expand the studies of DIAn by introducing another aspect of the modulation of the ∆EST which concerns with: i) the extension of the terminal benzenes with another fused benzene (i.e., forming terminal napthalenes) and ii) with the isomerization resulting from the fusion topology of these terminal benzenes. We will present a UV-Vis-NIR and Raman spectroscopic study of the new compounds. The variation of the spectra within molecular family will be discussed in connection with the variation of ∆EST and with the diradical character of the new molecules.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Medium Diradical Character, Small Hole and Electron Reorganization Energies and Ambipolar Transistors in Difluorenoheteroles

Four difluorenoheteroleshavinga centralquinoidalcore with the heteroringvaryingas furan,thiophene,its dioxidederivativeand pyrrolehave shownto be mediumcharacterdiradicals.Solid-statestructures,optical,photophysical,magnetic,and electrochemicalpropertieshave been discussedin termsof diradicalcharacter,variationof aromaticcharacterand captoda-tive effects(electronaffinity).Organicfield-effecttran-sistors(OFETs)have been prepared,showingbalancedholeand electronmobilitiesof the orderof103cm2V1s1or ambipolarchargetransportwhichisfirst inferredfrom their redoxamphoterism.Quantumchemicalcalculationsshow that the electricalbehaviorisoriginatedfrom the mediumdiradicalcharacterwhichproducessimilarreorganizationenergiesfor hole andelectrontransports.The visionof a diradicalas simulta-neouslybearingpseudo-holeand pseudo-electronde-fects might justifythe reducedvaluesof reorganizationenergiesfor both regimes.Structure-functionrelation-ships betweendiradicaland ambipolarelectricalbehav-ior are revealed.The authorsthankthe SpanishMinistryof ScienceandInnovation(projectsMINECO/FEDERPGC2018-098533-B-100,and PID2019-110305GB-I00),the Junta de Andalucíaand GeneralidadValenciana,Spain (UMA18FEDERJA057,P18-FR-4549and Prometeo/2019/076)and JSPS KAKENHIgrant (JP21K05042for S.-i.K.,JP21K04995and JP21H05489for R.K., JP21H01887and JP20K21173for M.N.).S.-i.K.gratefullyacknowledgesthe AsahiGlassFoundationforfinancialsupport.We also thankthe ResearchCentralServices(SCAI)of the Universityof Málaga,UnidaddeEspectroscopíaVibracional(Dra. Capely Dr. Zafra)andUnidadde OpticaNo-Linealy EspectroscopíaUltrarápida(Dr. Román).This work was partiallysupportedby theCooperativeResearchProgram“NetworkJoint ResearchCenterfor Materialsand Devices”(KyushuUniversity).WethankProf. ShuheiHigashibayashi(KeioUniversity)forassistancewith synthesis.Mass spectrometricdata werecollectedat HiroshimaUniversity(N-BARD:Ms. TomokoAmimoto).Theoreticalcalculationswere partlyperformedusing ResearchCenterfor ComputationalScience(R-CCS),Okazaki,Japan.F.N and Y.D. acknowledgesupportfrom“Valutazionedella Ricercadi Ateneo”(VRA)—Universityof Bologna.Y.D. acknowledgesMinisterodell’Universitàedella Ricerca(MUR)for her Ph.D. fellowship. Funding for open access charge: Universidad de Málaga / CBU

Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study

The version of record of this article, first published in British Journal of Cancer, is available online at Publisher’s website: https://doi.org/10.1038/s41416-023-02540-3Background: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer. Methods: A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively. Results: Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P < 0.03) and 12 months (P < 0.001) were independent prognostic factors for a shorter recurrence-free interval. Conclusions: Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer. Clinical trial registration: UMIN000007925

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Computational Study of the Effect of π-Congestion on the Singlet Biradical Character and Stacked Antiaromaticity in Acene Dimers

We demonstrated the computational study of the π-congestion effects in benzene, naphthalane, anthracene, teteracene, and pentacene dimers close with two positions at Ca···Ca’ and Cb···Cb’ to elucidate the singlet biradical characters as well as the stacked antiaromaticity. By extending the π-system from benzene to pentacene, the singlet biradical character increase whereas the stacked antiaromaticity decrease at near the transition state of [4+4]pericyclic reaction in ground state. Especially, the pentacene dimer exhibits large biradical character y0 = 61% with a weak antiaromaticity of NICSxx = +11 ppm at the distance of 2.80 Å between π-planes. These calculated results provided a unique idea to extract the similar electronic and magnetic natures as seen in transition state where the bond-order of the sp2 and sp3 carbon changes, like the graphite-to-diamond transformation

Theoretical Study on Exciton Dynamics in Dendritic Systems: Exciton Recurrence and Migration

The optical functionalities such as exciton recurrence and migration for dendritic systems, e.g., dendrimers, are investigated using the quantum master equation (QME) approach based on the ab initio molecular orbital configuration interaction (MOCI) method, which can treat both the coherent and incoherent exciton dynamics at the first principle level. Two types of phenylacetylene dendrimers, Cayley-tree dendrimer and nanostar dendrimer with anthracene core, are examined to elucidate the features of excion recurrence and migration motions in relation to their structural dependences. It is found that the nanostar dendrimer exhibits faster exciton migration from the periphery to the core than Cayley-tree dendrimer, which alternatively exhibits exciton recurrence motion among dendron parts in case of small relaxation parameters. Such strong structural dependence of exciton dynamics demonstrates the advantage of dendritic molecular systems for future applications in nano-optical and light-harvesting devices

Stacked-ring aromaticity from the viewpoint of the effective number of π-electrons

We theoretically examined the effective number of π-electrons in the closely π-stacked 4nπ electron dimers exhibiting stacked-ring aromaticity. Multi-configurational calculations for cyclobutadiene π-dimer models revealed that a double-triplet [1(T1T1)] character bearing 2 x (4n–2)π conjugated electrons + 4 formally unpaired electrons appears in the ground state at small stacking distances. Energy stabilization of the closely π-stacked dimers can be attributed to mixing intermolecular charge-transfer (CT) configurations. However, its energy gain would be insufficient for self-aggregation of the π-dimers with a stacking distance of ~3 Å