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1.
Resuscitation ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619295

RESUMO

AIM: To develop and validate a model for the early prediction of long-term neurological outcome in patients with non-traumatic out-of-hospital cardiac arrest (OHCA). METHODS: We analysed multicentre OHCA registry data of adult patients with non-traumatic OHCA who experienced return of spontaneous circulation (ROSC) and had been admitted to the intensive care unit between 2013 and 2017. We allocated 1329 (2013-2015) and 1025 patients (2016-2017) to the derivation and validation sets, respectively. The primary outcome was the dichotomized cerebral performance category (CPC) at 90 days, defined as good (CPC 1-2) or poor (CPC 3-5). We developed 2 models: model 1 included variables without laboratory data, and model 2 included variables with laboratory data available immediately after ROSC. Logistic regression with least absolute shrinkage and selection operator regularization was employed for model development. Measures of discrimination, accuracy, and calibration (C-statistics, Brier score, calibration plot, and net benefit) were assessed in the validation set. RESULTS: The C-statistic (95% confidence intervals) of models 1 and 2 in the validation set was 0.947 (0.930-0.964) and 0.950 (0.934-0.966), respectively. The Brier score of models 1 and 2 in the validation set was 0.063 and 0.062, respectively. The calibration plot showed that both models were well-calibrated to the observed outcome. Decision curve analysis indicated that model 2 was similar to model 1. CONCLUSION: The prediction tool containing detailed in-hospital information showed good performance for predicting neurological outcome at 90 days immediately after ROSC in patients with OHCA.

2.
Nat Biomed Eng ; 5(8): 926-940, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34373601

RESUMO

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells' chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.


Assuntos
Proteínas de Homeodomínio/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Pluripotentes/citologia , Animais , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/transplante , Condrogênese , Doenças do Colágeno/terapia , Meios de Cultura/química , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Pluripotentes/metabolismo , Polímeros/química , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Antígenos Thy-1/metabolismo , Engenharia Tecidual
3.
ESC Heart Fail ; 8(4): 3002-3013, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33934538

RESUMO

AIMS: It has been reported that congestive heart failure (CHF) readmission has not decreased in the last decade. It is also reported that CHF readmission is likely to occur shortly after discharge. We investigated whether an early follow-up at outpatient care within 2 weeks after discharge affects the long-term readmission rate and prognosis. METHODS AND RESULTS: We reviewed consecutive 1002 patients admitted to our hospital due to CHF. Two-hundred and fifty-nine patients who died in-hospital or were transferred to another hospital or readmitted within 2 weeks were excluded and 743 of discharged patients were analysed. We extracted contributing variables associated with heart failure (HF) readmission and the composite adverse outcome (all cause death or HF readmissions) by univariate and multivariate analysis. Multivariate analysis showed that the early follow-up was independently associated with freedom from HF readmission and the composite outcome. We divided these patients into two groups, with/without early follow-up and performed a propensity score-matching analysis (n = 259 each). HF readmission during 2 year follow-up was significantly less in the early follow-up group [P = 0.02, hazard ratio (HR) = 0.647, 95% confidence interval (CI) = 0.447-0.935] as well as the composite outcome was less in the early follow-up group (P = 0.01, HR = 0.643, 95% CI = 0.456-0.908). Medication adjustments were done in only 33.2% of the patients. Rates of HF readmissions were comparable regardless of whether or not medication adjustment was done at the early follow-up (P = 0.505, HR = 1.208, 95% CI = 0.692-2.106). CONCLUSIONS: The present study demonstrates that an early follow-up approach after discharge in CHF patients may improve the long-term prognosis. These results may not depend on medication adjustment but rather on modifying patient factors early after discharge.

4.
Stem Cell Reports ; 16(3): 610-625, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33636111

RESUMO

Chondrodysplasias are hereditary diseases caused by mutations in the components of growth cartilage. Although the unfolded protein response (UPR) has been identified as a key disease mechanism in mouse models, no suitable in vitro system has been reported to analyze the pathology in humans. Here, we developed a three-dimensional culture protocol to differentiate hypertrophic chondrocytes from induced pluripotent stem cells (iPSCs) and examine the phenotype caused by MATN3 and COL10A1 mutations. Intracellular MATN3 or COL10 retention resulted in increased ER stress markers and ER size in most mutants, but activation of the UPR was dependent on the mutation. Transcriptome analysis confirmed a UPR with wide-ranging changes in bone homeostasis, extracellular matrix composition, and lipid metabolism in the MATN3 T120M mutant, which further showed altered cellular morphology in iPSC-derived growth-plate-like structures in vivo. We then applied our in vitro model to drug testing, whereby trimethylamine N-oxide led to a reduction of ER stress and intracellular MATN3.

5.
Asian J Surg ; 44(1): 143-146, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32409242

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy greatly influences patients' postoperative course. Several evaluation methods have been used to assess the risk of clinically relevant POPF (CR-POPF) after pancreatoduodenectomy namely, the original, alternative, and updated alternative fistula risk scores (o-FRS, a-FRS, and ua-FRS, respectively). METHODS: We enrolled 106/179 patients who underwent pancreatoduodenectomy in our institution between April 2013 and Mar 2018. CR-POPF was defined as grade B and C POPF according to the 2016 definitions of the International Study Group on Pancreatic Surgery. RESULTS: Pancreatic gland texture was the only significant risk factor for CR-POPF (p = 0.007). The CR-POPF incidence increased significantly according to the risk groups defined by both o-FRS (p = 0.004) and a-FRS (p = 0.004). The area under the curve for o-FRS, a-FRS, and ua-FRS was 0.693, 0.693, and 0.671, respectively. CONCLUSION: o-FRS, a-FRS, and ua-FRS were almost equally useful for risk evaluation for CR-POPF after pancreatoduodenectomy. Further studies, especially for preoperative objective evaluation of pancreatic gland texture, are needed for more useful and accurate risk evaluation.


Assuntos
Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pâncreas/patologia , Fístula Pancreática/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco
6.
JBJS Case Connect ; 10(2): e0228, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649109

RESUMO

CASES: We report 2 cases of missing condylar region associated with severe elbow trauma treated with our new surgical technique and present the outcomes at the 9- and 10-year follow-ups. Our method focused on anatomical isometric point reconstruction, which consisted of the reconstruction of the missing condylar region with the iliac bone and the collateral ligament with the palmaris longus tendon. CONCLUSIONS: This injury is rare, and treatment is challenging because of the difficulty in identifying the isometric point. Both patients achieved good elbow function. The bone defect region was almost remodeled with minimal bone tunnel enlargement. Overall, our technique can provide positive results.


Assuntos
Artroplastia/métodos , Transplante Ósseo , Ligamento Colateral Ulnar/cirurgia , Articulação do Cotovelo/lesões , Fraturas Expostas/cirurgia , Adulto , Humanos , Masculino , Adulto Jovem
7.
J Arrhythm ; 36(3): 448, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32528570
8.
Orphanet J Rare Dis ; 15(1): 122, 2020 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448372

RESUMO

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disease characterized by heterotopic ossification (HO) in soft tissues and caused by a mutation of the ACVR1A/ALK2 gene. Activin-A is a key molecule for initiating the process of HO via the activation of mTOR, while rapamycin, an mTOR inhibitor, effectively inhibits the Activin-A-induced HO. However, few reports have verified the effect of rapamycin on FOP in clinical perspectives. METHODS: We investigated the effect of rapamycin for different clinical situations by using mice conditionally expressing human mutant ACVR1A/ALK2 gene. We also compared the effect of rapamycin between early and episode-initiated treatments for each situation. RESULTS: Continuous, episode-independent administration of rapamycin reduced the incidence and severity of HO in the natural course of FOP mice. Pinch-injury induced HO not only at the injured sites, but also in the contralateral limbs and provoked a prolonged production of Activin-A in inflammatory cells. Although both early and injury-initiated treatment of rapamycin suppressed HO in the injured sites, the former was more effective at preventing HO in the contralateral limbs. Rapamycin was also effective at reducing the volume of recurrent HO after the surgical resection of injury-induced HO, for which the early treatment was more effective. CONCLUSION: Our study suggested that prophylactic treatment will be a choice of method for the clinical application of rapamycin for FOP.


Assuntos
Miosite Ossificante , Ossificação Heterotópica , Receptores de Ativinas Tipo I/genética , Animais , Humanos , Camundongos , Mutação , Miosite Ossificante/tratamento farmacológico , Miosite Ossificante/genética , Ossificação Heterotópica/tratamento farmacológico , Ossificação Heterotópica/genética , Sirolimo/farmacologia , Sirolimo/uso terapêutico
9.
J Physiol Sci ; 70(1): 15, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066374

RESUMO

Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl- currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl- channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.


Assuntos
Canais de Cloreto/metabolismo , Neoplasias Gástricas , Linhagem Celular Tumoral , Ensaios de Migração Celular , Proliferação de Células , Canais de Cloreto/genética , Clonagem Molecular , Regulação Neoplásica da Expressão Gênica , Humanos , Potenciais da Membrana/fisiologia , Técnicas de Patch-Clamp
10.
Sci Rep ; 9(1): 12271, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439861

RESUMO

The pathophysiology of non-pulmonary vein (PV) triggers of atrial fibrillation (AF) is unclear. We hypothesized that left atrial non-PV (LANPV) triggers are associated with atrial tissue degeneration. This study analyzed 431 patients that underwent catheter ablation (mean age 62 yrs, 303 men, 255 paroxysmal AF [pAF] patients). Clinical and electrophysiological characteristics of non-PV trigger were analyzed. Fifty non-PV triggers in 40 patients (9.3%) were documented; LANPV triggers were the most prevalent (n = 19, 38%). LANPV triggers were correlated with non-paroxysmal AF (non-pAF) (OR 3.31, p = 0.04) whereas right atrial non-PV (RANPV) triggers (n = 14) and SVC triggers (n = 17) were not. The voltage at the LANPV sites during SR was 0.3 ± 0.16 mV (p < 0.001 vs. control site). Low-voltage areas (LVAs) in the LA were significantly greater in non-pAF compared to pAF (14.2% vs. 5.8%, p < 0.01). RANPV trigger sites had preserved voltage (0.74 ± 0.48 mV). Long-term outcomes of patients with non-PV triggers treated with tailored targeting strategies were not significantly inferior to those without non-PV triggers. In conclusion, non-PV triggers arise from the LA with degeneration, which may have an important role in AF persistence. A trigger-oriented, patient-tailored ablation strategy considering LA voltage map may be feasible and effective in persistent/recurrent AF.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Feminino , Seguimentos , Átrios do Coração/fisiopatologia , Átrios do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares
11.
Nat Biomed Eng ; 3(7): 558-570, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31182836

RESUMO

The recapitulation of bone formation via the in vitro generation of bone-like nodules is frequently used to understand bone development. However, current bone-induction techniques are slow and difficult to reproduce. Here, we report the formation of bone-like nodules within ten days, via the use of retinoic acid (RA) to induce the osteogenic differentiation of human induced pluripotent stem cells (hiPSCs) into osteoblast-like and osteocyte-like cells that create human bone tissue when implanted in calvarial defects in mice. We also show that the induction of bone formation depends on cell signalling through the RA receptors RARα and RARß, which simultaneously activate the BMP (bone morphogenetic protein) and Wnt signalling pathways. Moreover, by using patient-derived hiPSCs, the bone-like nodules recapitulated the osteogenesis-imperfecta phenotype, which was rescued via the correction of disease-causing mutations and partially by an mTOR (mechanistic target of rapamycin) inhibitor. The method of inducing bone nodules may serve as a fast and reproducible model for the study of the formation of both healthy and pathological bone.


Assuntos
Osso e Ossos/patologia , Osso e Ossos/fisiologia , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Osteogênese/fisiologia , Animais , Proteínas Morfogenéticas Ósseas , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Técnicas In Vitro , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Nus , Camundongos SCID , Mutação , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Fenótipo , Receptores do Ácido Retinoico/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Transplante , Tretinoína/farmacologia , Via de Sinalização Wnt
12.
J Med Genet ; 56(9): 622-628, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31015262

RESUMO

BACKGROUND: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity. METHODS: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments. RESULTS: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype. CONCLUSIONS: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Alelos , Hérnia Diafragmática/diagnóstico , Hérnia Diafragmática/genética , Mutação com Perda de Função , Escoliose/congênito , Escoliose/diagnóstico , Coluna Vertebral/anormalidades , Proteínas com Domínio T/genética , Biologia Computacional/métodos , Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação de Sentido Incorreto
13.
J Arrhythm ; 35(2): 223-229, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31007786

RESUMO

Background: Induction test of atrial fibrillation (AF) is one of endpoint measures in catheter ablation (CA). However, its predictive value in long-term outcome remains controversial. Methods: Ninety-eight patients (61 years, 77 males) with persistent AF who underwent pulmonary vein antrum isolation-based CA were retrospectively analyzed. We determined whether inducibility of AF/atrial tachyarrhythmias (AT) by atrial burst pacing at the end of CA and other characteristics were associated with the recurrence of AF/AT. Atrial burst pacing was performed with 30-beat from the coronary sinus; increasing from 240 to 320 ppm. Inducibility was defined as AF/AT lasting ≥5 minutes following atrial burst pacing. Results: AF/AT was induced in 50 patients (51%). During 1 year of follow-up, 71 patients (72.4%) had no recurrence of AF/AT. A logistic regression analysis showed that female gender (OR 3.8; P = 0.02), multiple sessions (OR 3.5; P = 0.02), and early recurrence of AF/AT (OR 5.3; P = 0.004) were associated with clinical recurrence. AF/AT Inducibility was not associated with clinical recurrence (P = 0.65). A subanalysis in patients with enlarged LA (LA diameter ≥45 mm, n = 40) showed that AF/AT inducibility was associated with recurrence (OR 8.1; P = 0.04). The positive and negative predictive values of AF/AT inducibility for AF/AT recurrence were 41 and 89%, respectively. Negative predictive value was increased to 92.3% when the inducibility was defined as AF/AT of ≥30 seconds following atrial burst pacing. Conclusions: AF/AT inducibility cannot predict long-term clinical recurrence in patients with persistent AF. However, it may have a prognostic value especially in patients with enlarged LA.

14.
Gan To Kagaku Ryoho ; 46(1): 65-69, 2019 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-30765645

RESUMO

A 69-year-old man with chronic gastritis, reflux esophagitis, esophageal hiatal hernia, and history of appendicitis surgery complained of difficulty swallowing. Upper gastrointestinal endoscopy revealed a 10 cm sized Type 3 gastric cancer. Immunostaining was positive for chromogranin A(2+), synaptophysin(3+), CD56(-), and Ki-67>70%. Contrast computed tomography(CT)showed upper gastric wall thickening, and #1, #3, #7, #8a, and #11p enlarged lymph nodes but no distant metastasis. We diagnosed gastric cancer, UM, Less, Type 3, gastric neuroendocrine carcinoma, cT4aN3M0P0CY0, Stage ⅢC. We administered 2 courses of CDDP plus CPT-11 chemotherapy, and a partial response was obtained for the primary gastric lesion and lymph node metastases. We subsequently performed open distal gastrectomy, D2 lymph node dissection, and splenectomy. Pathological examination confirmed that the lesion was gastric cancer, U, Less, Type 3, gastric neuroendocrine carcinoma, MP, Ul-Ⅱ(+), int, INF b, ly2, v0, PM0, DM0, R0, ypT2N2, Stage ⅡB, with a therapeutic value of Grade 2. The patient was discharged on day 15 after the surgery and received 2 courses of adjuvant chemotherapy with CDDP plus CPT-11. Nine months after the surgery, metastasis of the left adrenal grand was found. We performed open left adrenal gland resection and administered adjuvant S-1 chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Neuroendócrino , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Cisplatino/administração & dosagem , Combinação de Medicamentos , Gastrectomia , Humanos , Irinotecano/administração & dosagem , Metástase Linfática , Masculino , Ácido Oxônico , Neoplasias Gástricas/tratamento farmacológico , Tegafur
15.
J Cardiol Cases ; 18(2): 52-56, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30279910

RESUMO

Although cardiac resynchronization therapy (CRT) is beneficial in patients with heart failure (HF) and left ventricular dyssynchrony, its effectiveness has not been established in patients with decompensated HF on mechanical support. Here, we report two patients with decompensated HF depending on inotropes and intra-aortic balloon pumping (IABP), who were rescued by urgent CRT implantations. Both patients had non-ischemic cardiomyopathy with wide QRS of left bundle brunch block. IABP could be weaned just after introducing CRT. CRT can dramatically improve hemodynamics even in severely decompensated HF, and thus could be considered when left ventricular dyssynchrony is present. .

17.
Chem Sci ; 7(5): 3240-3247, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29997816

RESUMO

We describe the design of two types of cyclophanes that generate dynamic helicity through the twisting of two planes in a clockwise or counterclockwise direction to give (M)- or (P)-helicity. We used a rectangular and anisotropic plane of 1,2,4,5-tetrakis(phenylethynyl)benzene (TPEB), since it can be stacked in pairs in two ways, in parallel or orthogonally, to be identified as distinct cyclophane molecules. We adopted a synthetic strategy for obtaining these two cyclophanes as a mixture using a macrocyclic intermediate that possessed two rotatable phenyl rings. We introduced necessary parts into the rotators to give a mixture of rotational isomers leading to a parallel or orthogonal arrangement of TPEBs, and then doubly bridged two planes of TPEB to form quadruply-bridged cyclophanes. We consider that such two planes in each cyclophane are in an "obverse and/or reverse" relation. In each cyclophane, we found unique dynamic helical forms with (M)- or (P)-helicity as well as an inherently non-chiral form. Normally, the screw-sense preference of dynamic helicity would be controlled through the intramolecular or supramolecular transmission of central chirality, when a chiral auxiliary is attached to the cyclophanes or a chiral guest is allowed to form a complex with the cyclophanes. In a case where two different substitution groups were used on bridging units to generate planar chirality in each cyclophane, the screw-sense preference was controlled through the arrangement of these substitution groups, and did not depend on the transmission of central chirality. Two different substitution groups desymmetrize the enantiomeric forms with (M)- or (P)-helicity generated in each dynamic helical cyclophane so that two dynamic helical forms with (M)- or (P)-helicity can be in a diastereomeric relation. Thus, a particular screw sense of dynamic helicity can be preferred, regardless of whether or not the two substitution groups possess some chiral element.

18.
Chem Sci ; 6(11): 6592-6600, 2015 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28757962

RESUMO

We describe a quantitative analysis of the complexation-induced inversion of a screw-sense preference based on a conformationally dynamic double-helix structure in a macrocycle. The macrocycle is composed of two twisting units (terephthalamide), which are spaced by two strands (1,3-bis(phenylethynyl)benzene), and is designed to generate a double-helix structure through twisting about a C2 axis in a conrotatory manner. The attachment of chiral auxiliaries to the twisting units induces a helical preference for a particular sense of (M)- or (P)-helicity through the intramolecular transmission of chirality to dynamic double helices. The twisting unit can also act as a binding site for capturing a guest molecule, and, in a complexed state, the preferred screw sense of the dynamic double-helix structure is reversed to exhibit the contrary preference. We quantitatively monitored the complexation-induced inversion of the screw-sense preference using 1H NMR spectroscopy, which enabled us to observe independently two species with (M)- or (P)-helicity in both the absence and presence of a guest molecule. Inversion of the screw-sense preference was induced upon complexation with an achiral guest as well as a chiral guest.

19.
Org Biomol Chem ; 12(47): 9532-8, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25223581

RESUMO

We designed hexakis(phenylethynyl)benzene derivatives with a tertiary amide group on each blade to achieve a helically biased propeller arrangement through the complexation-induced intramolecular transmission of point chirality. A hydrogen-bonding ditopic guest was captured at two amide groups, and thus could pair two neighboring blades to form a supramolecular cyclic structure, in which an auxiliary chiral group associated with a blade acted as a chiral handle to control the helical bias, while the chiral auxiliary did not exert any helical influence on the dynamic helicity in the absence of a guest due to the high flexibility of each blade.

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