Risk factors for placenta accreta spectrum in pregnancies conceived after frozen-thawed embryo transfer in a hormone replacement cycle.

OBJECTIVE: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC. STUDY DESIGN: We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration. RESULTS: PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44). CONCLUSION: Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies.

The Cellular Accumulation of Vehicle Exhaust Particulates Changes the Acidic pH Environment of Lysosomes in BEAS-2B Airway Epithelial Cells.

Many people are exposed every day to vehicle exhaust particulates (VEPs), which are thought to be taken up by epithelial cells that are the first barrier in our biological defense. The study aim was to investigate how VEPs are processed in the lysosomal degradation system. BEAS-2B airway epithelial cells easily ingest VEPs and have been shown to accumulate in cells for several days, but no elevated cytotoxicity was observed over that time period. An analysis of 3D images confirmed the presence of VEPs in or near lysosomes, and an accumulation of VEPs resulted in an increase in the normal acidic pH in lysosomes and the extracellular release of the lysosomal enzyme ß-hexosaminidase. Epithelial cells were thought to activate the lysosome-mediated secretion of extracellular vesicles to avoid damage caused by non-degradable foreign substances, such as VEPs, and as a side reaction, the acidic pH environment of the lysosomes could not be maintained.

Related Factors for Abnormal Umbilical Cord Insertion: A Preliminary Study Based on Two Regional Tertiary Hospitals in Japan.

OBJECTIVE: We elucidated maternal background, perinatal complications and outcomes as potential related factors for abnormal umbilical cord insertion (ACI) -velamentous and marginal- based on data from two tertiary perinatal hospitals in Japan. MATERIALS AND METHODS: The subjects were 3,741 women with singleton pregnancies who delivered at ≥ 22 weeks' gestation in Kurume University Hospital and St. Mary's Hospital, Kurume, Japan from January 2013 to December 2015. They were divided into two groups, with and without ACI. Related factors were extracted from the medical registry database of the perinatal committee in the Japan Society of Obstetrics and Gynecology. Random Forest and stepwise logistic regression models were employed to evaluate their impact on ACI. RESULTS: Related factors for ACI in terms of maternal background and perinatal complications and outcomes were: pre-pregnancy smoking habit (adjusted odds ratio, OR, 3.38; 95% confidence interval, CI, 2.20-5.20; P < 0.0001); conception using assisted reproductive technology (adjusted OR, 2.00; 95% CI, 1.11-3.60; P = 0.021); placenta previa (adjusted OR, 4.74; 95% CI, 2.06-10.90; P < 0.0001); fetal growth restriction (adjusted OR, 2.43; 95% CI, 1.49-3.97; P < 0.0001); and non-reassuring fetal status during labor (adjusted OR, 2.74; 95% CI, 1.71-4.38; P < 0.0001). CONCLUSION: This was a preliminary study attempting to elucidate related factors for ACI in a Japanese population. However, further large-scale studies are needed in Japan.

Exponential increase of the gestational-age-specific incidence of preeclampsia onset (COPE study): a multicenter retrospective cohort study in women with maternal check-ups at <20 weeks of gestation in Japan.

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at <32 weeks of gestation. This was based on the presence of "dual peaks" (30-31 and 34-35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were "dual peaks" in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at <20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at <32 and <34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R2 values (0.975, 0.976, and 0.964, respectively). There were no "dual peaks" in the prevalence rates of women with SPE/PE, PE, and PE with severe hypertension. In conclusion, the absence of "dual peaks" refutes the previous rationale of EO-PE being defined as PE at <32 weeks of gestation. Further studies to determine an appropriate definition of EO-PE/SPE are needed.

Estimation of the Viscosity of an Antibody Solution from the Diffusion Interaction Parameter.

Understanding a monoclonal antibody's (MAb) physicochemical properties early in drug discovery is important for determining developability. Viscosity is important because antibodies with high viscosity have limited administration routes. Predicting the viscosity of highly concentrated MAb solutions is therefore essential for assessing developability. Here, we measured the viscosity and diffusion interaction coefficient (kDiff) of 3 MAbs under 15 different formulation conditions (pH and salt) and evaluated correlations between parameters. We also used a computational approach to identify the key factors underlying differences in concentration-dependent curves for viscosity among the MAbs and formulation conditions. Results showed that viscosity increased exponentially at high concentrations, and that this concentration-dependency could be predicted from kDiff. Attempts to set viscosity criterion for use by subcutaneous (SC) and intramuscular (IM) administration suggested that solutions with kDiff greater than -20 mL/g may be candidates. Computational analysis suggested that the presence of a large negative charge in the complementarity determining region (CDR) is a major factor underlying the difference in concentration-dependency among the three MAbs under different formulation conditions. Because it is possible to predict the administration form of antibody solutions, determination of kDiff at the early discovery stage may be essential for effective antibody development.

A case of ventricular noncompaction associated with heterotaxy and atrioventricular block diagnosed at 15 weeks of gestation using superb microvascular imaging.

We present a case of fetal atrioventricular block, heterotaxy, and ventricular noncompaction observed longitudinally from the first to early second trimesters using B-mode and Doppler imaging, including superb microvascular imaging. At 12 weeks of gestation, the atrial and ventricular rates were 133 and 67 beats/min, respectively, and dextrocardia was noted. At 15 weeks of gestation, detailed sonography revealed ventricular septal defect, interruption of the inferior vena cava, dilated azygos vein, and double-outlet right ventricle. In addition, superb microvascular imaging revealed irregular contours in the anatomical left ventricular wall, indicating prominent trabeculations of the ventricle, which were characteristic findings of ventricular noncompaction. At 21 weeks of gestation, intrauterine fetal death occurred, and the autopsy revealed complex congenital heart disease, including ventricular noncompaction.

Clinical Utility of Endometrial Cell Block Cytology in Postmenopausal Women.

OBJECTIVE: To investigate the diagnostic utility of endometrial (EM) cell block (CB) cytology for the detection of intrauterine malignancy in postmenopausal women. METHODS: We reviewed the medical records of 104 postmenopausal women between January 2012 and November 2014. We reviewed symptoms upon admission, body mass index, parity, transvaginal ultrasonographic findings, and histopathological results based on CB and conventional cytology. RESULTS: The mean age was 62.6 (range 48-95) years. The mean menopausal age was 50.8 years and the mean duration of menopause was 12.0 years. The sensitivity of CB and conventional cytology was 82.3% (29/35) and 85.7% (30/35) and the specificity was 98.6% (68/69) and 94.2% (65/69), respectively. The sensitivity and specificity of CB cytology combined with conventional cytology were 82.3% (29/35) and 94.2% (65/69), respectively. The predictive values for EM hyperplasia and type-II carcinoma were 100 and 85.7%, respectively. CONCLUSION: CB cytology provides specimens for examination in a single outpatient session. Additionally, immunohistochemical staining can provide useful information for histological diagnosis. A combination of CB and conventional cytology can improve the diagnostic accuracy of EM lesions and may be a valid method for screening in postmenopausal women.

Solvation Structure of Imidazolium Cation in Mixtures of [C4mim][TFSA] Ionic Liquid and Diglyme by NMR Measurements and MD Simulations.

Interactions of 1-butyl-3-methylimidazolium cation ([C4mim]+) with bis(trifluoromethanesulfonyl)amide anion ([TFSA]-) and diethyleneglycol dimethyl ether (diglyme) in mixtures of [C4mim][TFSA] ionic liquid and diglyme have been investigated using 1H and 13C NMR spectroscopy and molecular dynamics (MD) simulations. The results of NMR chemical shift measurements and MD simulations showed that the diglyme oxygen atoms have contact with the imidazolium hydrogen atoms of [C4mim]+ in the mixtures. The contact between the hydrogen atoms of imidazolium and the oxygen atoms of [TFSA]- remains even when the diglyme mole fraction (xdiglyme) increases up to 0.9. However, the coordination numbers of the hydrogen atoms of [C4mim]+ with oxygen atoms of diglyme increase with xdiglyme. The [TFSA]- anions around [C4mim]+ are not completely replaced by diglyme even at xdiglyme > 0.9. The MD simulations revealed that the diglymes also have contact with the butyl group of [C4mim]+. The methyl groups of diglyme prefer to have contact with the terminal methyl group of the butyl group, whereas the diglyme oxygen atoms prefer to have contact with the methylene group connected to the imidazolium ring of [C4mim]+.

Two cases of acute limbic encephalitis in which symptoms improved as a result of laparoscopic salpingo-oophorectomy.

Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is an autoimmune form of limbic encephalitis. Eighty percent of patients with anti-NMDA receptor (NMDAR) encephalitis are women, and 39% of those women are reported to have an ovarian teratoma also. When a tumor is also present, prompt surgery can prevent the development of more severe symptoms or the prolongation of symptoms of encephalitis. The current authors encountered two cases in which anti-NMDAR encephalitis was suspected. In these cases, abdominal computed tomography (CT) revealed an ovarian teratoma and both patients underwent a laparoscopic salpingo-oophorectomy. Both patients underwent surgery before a definitive diagnosis was made. Findings in one case did not lead to a diagnosis of anti-NMDAR encephalitis, but symptoms rapidly improved after surgery in both cases. Laparoscopic surgery is minimally invasive, so this approach may be the first step in a treatment algorithm for treatment of a tumor in a patient with anti-NMDAR encephalitis.

Targeted transgene insertion into the CHO cell genome using Cre recombinase-incorporating integrase-defective retroviral vectors.

Retroviral vectors have served as efficient gene delivery tools in various biotechnology fields. However, viral DNA is randomly inserted into the genome, which can cause problems, such as insertional mutagenesis and gene silencing. Previously, we reported a site-specific gene integration system, in which a transgene is integrated into a predetermined chromosomal locus of Chinese hamster ovary (CHO) cells using integrase-defective retroviral vectors (IDRVs) and Cre recombinase. In this system, a Cre expression plasmid is transfected into founder cells before retroviral transduction. In practical applications of site-specific gene modification such as for hard-to-transfect cells or for in vivo gene delivery, both the transgene and the Cre protein into retroviral virions should be encapsulate. Here, we generated novel hybrid IDRVs in which viral genome and enzymatically active Cre can be delivered (Cre-IDRVs). Cre-IDRVs encoding marker genes, neomycin resistance and enhanced green fluorescent protein (EGFP), flanked by wild-type and mutated loxP sites were produced using an expression plasmid for a chimeric protein of Cre and retroviral gag-pol. After analyzing the incorporation of the Cre protein into retroviral virions by Western blotting, the Cre-IDRV was infected into founder CHO cells, in which marker genes (hygromycin resistance and red fluorescent protein) flanked with corresponding loxP sites are introduced into the genome. G418-resistant colonies expressing GFP appeared and the site-specific integration of the transgene into the expected chromosomal site was confirmed by PCR and sequencing of amplicons. Moreover, when Cre-IDRV carried a gene expression unit for a recombinant antibody, the recombinant cells in which the antibody expression cassette was integrated in a site-specific manner were generated and the cells produced the recombinant antibody. This method may provide a promising tool to perform site-specific gene modification according to Cre-based cell engineering. Biotechnol. Bioeng. 2016;113: 1600-1610. © 2016 Wiley Periodicals, Inc.

Microscopic interactions of the imidazolium-based ionic liquid with molecular liquids depending on their electron-donicity.

Microscopic interactions of an imidazolium-based ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (C2mimTFSI), with dimethyl sulfoxide (DMSO), methanol (MeOH), and acetonitrile (AN) have been analyzed by means of Raman, attenuated total reflectance infrared (ATR-IR), (1)H and (13)C NMR spectroscopy techniques. The magnitude of the red-shift of the C(2)-H vibration mode of the imidazolium ring and the deshielding of the C(2)-H hydrogen and carbon atoms, compared with that of the other atoms of the ring or the anion, indicated a strong interaction between the C(2)-H hydrogen atom and the molecular liquids in the following order; DMSO ≫ MeOH > AN. This correlates with the order of the electron donicities of these molecular liquids which allows us to suggest a hydrogen bonding character of these interactions. The behavior of S= O vibration of DMSO as a function of the DMSO molar fraction xDMSO also suggested that DMSO molecules are stoichiometrically hydrogen-bonded with the three hydrogen atoms, C(2,4,5)-H, of the ring. In contrast, the hydrogen bonding between MeOH and the C(4,5)-H atoms is much weaker than that in DMSO. AN hardly forms hydrogen bonds with the C(4,5)-H atoms. Instead, AN molecules may interact with the imidazolium ring through the π-π interaction. The interactions between the imidazolium ring and the molecular liquids lead to the loosening of the TFSI anion from the cation; this correlates with both the blue-shift of the S=O stretching vibration of TFSI and the deshielding of the trifluoromethyl carbon atoms with an increase in the molar fraction of the molecular liquid xML. The latter is weak in the MeOH solutions, and may be explained by the possible hydrogen bonding of the MeOH hydroxyl group as an electron-acceptor with the TFSI anion. Furthermore, the organization of MeOH molecules around the ethyl and methyl groups of the cation is discussed in terms of the chemical shift of the hydrogen and carbon atoms in these groups as a function of xML.

SANS, ATR-IR, and 1D- and 2D-NMR studies of mixing states of imidazolium-based ionic liquid and aryl solvents.

The mixing states of imidazolium-based ionic liquid, 1-dodecyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide (C12mim(+)TFSA(-)), and two aryl solvents toluene and α,α,α-trifluorotoluene (TFT) have been clarified on both meso- and microscopic scales using small-angle neutron scattering (SANS) and ATR-IR techniques. To elucidate the interactions between C12mim(+)TFSA(-) and aryl solvent molecules from the change in the electron densities of C12mim(+) and TFSA(-), 1D-NMR measurements for (1)H and (13)C atoms have been conducted on C12mim(+)TFSA(-)-aryl solvent solutions as a function of the aryl solvent mole fraction. In addition, the interactions between the dodecyl chain of C12mim(+) and aryl solvent molecules have been observed using 2D-NMR techniques of (1)H{(1)H} ROESY and (19)F{(1)H} HOESY. These results have been compared with those of benzene solutions previously investigated. The SANS measurements have shown that toluene is heterogeneously mixed with C12mim(+)TFSA(-) as well as benzene. However, the heterogeneity of the toluene solutions is slightly lower than that of the benzene solutions. In contrast, TFT is homogeneously mixed with the ionic liquid at least on the present SANS scale. The substituent effects of the three aryl solvent molecules of benzene, toluene, and TFT on the mixing states of the solutions have been discussed in terms of the cation-π interaction between the imidazolium and phenyl rings and the interaction between the dodecyl group and aryl solvent molecules.

SANS, infrared, and 7Li and 23Na NMR studies on phase separation of alkali halide-acetonitrile-water mixtures by cooling.

Phase separation of alkali halide (MX) (M = Li+, Na+, and K+ and X = Cl­ and Br­)­acetonitrile (AN)­water mixtures by cooling has been investigated at the molecular level. The phase diagram obtained for the MX­AN­H2O ternary systems showed that the temperatures of phase separation for the mixtures with MCl are higher than those with MBr. The phase-separation temperatures of the mixtures with MCl and MBr are higher in the sequence of NaX > KX > LiX, although the magnitude of the hydration enthalpies for the alkali metal ions is larger in the sequence of Li+ > Na+ > K+. To elucidate the reasons for the sequence of phase separation on the meso- and microscopic scales, small-angle neutron scattering (SANS), infrared (IR), and 7Li and 23Na NMR measurements have been conducted on MX­AN­water mixtures with lowering temperature. The results of SANS and IR experiments showed that the mechanism of phase separation of the mixtures by cooling is the same among all of the mixtures but did not clearly reveal the reasons for the phase separation sequence. In contrast, the spin­lattice relaxation rates and the chemical shifts of 7Li and 23Na NMR for the mixtures suggested the different solvation structure of Li+ and Na+ in the mixtures. In conclusion, the solvation of acetonitrile molecules for Li+ and the formation of Li+­X­ contact ion pairs in the mixtures cause the weakest effect of LiX on phase separation of the mixtures by cooling among the alkali metal ions.

Proton acceleration to 40 MeV using a high intensity, high contrast optical parametric chirped-pulse amplification/Ti:sapphire hybrid laser system.

Using a high-contrast (10(10):1) and high-intensity (10(21) W/cm(2)) laser pulse with the duration of 40 fs from an optical parametric chirped-pulse amplification/Ti:sapphire laser, a 40 MeV proton bunch is obtained, which is a record for laser pulse with energy less than 10 J. The efficiency for generation of protons with kinetic energy above 15 MeV is 0.1%.

Aggregation of 1-dodecyl-3-methylimidazolium nitrate in water and benzene studied by SANS and 1H NMR.

Aggregation of imidazolium-based ionic liquid, C(12)mim(+)NO(3)(-), in both polar solvent of water and nonpolar solvent of benzene was elucidated by electrical conductivity, small-angle neutron scattering (SANS), and (1)H NMR measurements. The electrical conductivities of C(12)mim(+)NO(3)(-)-water solutions at 298 K as a function of ionic liquid concentration showed a break point at 8.4 mmol dm(-3) as a cmc. However, those of C(12)mim(+)NO(3)(-)-benzene solutions drastically increase in accordance with a cubic function of concentration, but without a break point. The SANS profiles of both aqueous and benzene solutions obviously differ from each other. The profiles of the aqueous solutions indicated the formation of polydisperse spherical micelles. Those of the benzene solutions revealed Ornstein-Zernike behavior. Thus, C(12)mim(+)NO(3)(-) forms clusters in the benzene solutions, but the shape of clusters is indefinite. On the basis of the (1)H NMR chemical shifts of the aqueous solutions, the effect of nitrate on the formation of micelles was discussed on a microscopic scale. Furthermore, the interactions among C(12)mim(+), NO(3)(-), and benzene molecules in the benzene solutions were considered according to the (1)H NMR data.

Amide-induced phase separation of hexafluoroisopropanol-water mixtures depending on the hydrophobicity of amides.

Amide-induced phase separation of hexafluoro-2-propanol (HFIP)-water mixtures has been investigated to elucidate solvation properties of the mixtures by means of small-angle neutron scattering (SANS), (1)H and (13)C NMR, and molecular dynamics (MD) simulation. The amides included N-methylformamide (NMF), N-methylacetamide (NMA), and N-methylpropionamide (NMP). The phase diagrams of amide-HFIP-water ternary systems at 298 K showed that phase separation occurs in a closed-loop area of compositions as well as an N,N-dimethylformamide (DMF) system previously reported. The phase separation area becomes wider as the hydrophobicity of amides increases in the order of NMF < NMA < DMF < NMP. Thus, the evolution of HFIP clusters around amides due to the hydrophobic interaction gives rise to phase separation of the mixtures. In contrast, the disruption of HFIP clusters causes the recovery of the homogeneity of the ternary systems. The present results showed that HFIP clusters are evolved with increasing amide content to the lower phase separation concentration in the same mechanism among the four amide systems. However, the disruption of HFIP clusters in the NMP and DMF systems with further increasing amide content to the upper phase separation concentration occurs in a different way from those in the NMF and NMA systems.

Temporal contrast enhancement of petawatt-class laser pulses.

We demonstrate the temporal contrast enhancement in a petawatt-class Ti:sapphire chirped-pulse amplification (CPA) laser system. An extra saturable absorber, introduced downstream after a low-gain optical parametric chirped-pulse amplification (OPCPA) preamplifier, has improved the temporal contrast in the system to 1.4×10(12) on the subnanosecond time scale at 70 TW power level. We have achieved 28 J of uncompressed broadband output energy with this system, indicating the potential for reaching peak powers near 600 TW.

Clusters of imidazolium-based ionic liquid in benzene solutions.

Cluster formation of 1-dodecyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide (C(12)mim(+)TFSA(-)) in benzene solutions was investigated using small-angle neutron scattering (SANS), NMR, attenuated total reflectance infrared (ATR-IR), and large-angle X-ray scattering (LAXS) techniques. The SANS measurements revealed that C(12)mim(+)TFSA(-) is heterogeneously mixed with benzene in the narrow range of benzene mole fraction 0.9 ≤ x(C6D6) ≤ 0.995 with a maximum heterogeneity at x(C6D6) ≈ 0.99. The NMR results suggested that the imidazolium ring is sandwiched between benzene molecules through the cation-π interaction. Moreover, TFSA(-) probably interacts with the imidazolium ring even in the range of x(C6H6) ≥ 0.9. Thus, the imidazolium rings, benzene molecules, and TFSA(-) would form clusters in the C(12)mim(+)TFSA(-)-benzene solutions. The LAXS measurements showed that the distance between the imidazolium ring and benzene is ∼3.8 Å with that between the benzene molecules of ∼7.5 Å. On the basis of these results, we discussed a plausible reason for the liquid-liquid equilibrium of the C(12)mim(+)TFSA(-)-benzene system.

N,N-dimethylformamide-induced phase separation of hexafluoroisopropanol-water mixtures.

We found that addition of N,N-dimethylformamide (DMF) induces phase separation of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)-water mixtures. The phase diagram of a DMF-HFIP-water ternary system at 298 K showed that phase separation occurs in a closed-loop area in the water-rich mole fraction range of x(H(2)O) > ∼0.4. To clarify the mechanism of DMF-induced phase separation of DMF-HFIP-water mixtures at the molecular level, small-angle neutron scattering (SANS) and (1)H and (13)C NMR measurements were conducted on the mixtures with varying DMF concentrations along a volume ratio of HFIP to water of 1 : 1 (x(S)(HFIP) = 0.147). Additionally, the solvation structure of DMF in water and HFIP-water mixtures was elucidated by molecular dynamics (MD) simulations. The SANS results revealed that the inherent heterogeneity of HFIP-water mixtures is increased with increasing DMF concentration toward the lower phase separation concentration, but decreased when the DMF concentration further increased beyond the upper phase separation one. (1)H and (13)C NMR measurements and MD simulations suggested that preferential solvation of the hydrophobic moiety of DMF by HFIP is the main driver of the phase behaviour of the DMF-HFIP-water system.

Effects of the alkyl-chain length on the mixing state of imidazolium-based ionic liquid-methanol solutions.

Effects of the alkyl-chain length of the imidazolium cation on the mixing state of imidazolium-based ionic liquids, 1-alkyl-3-methylimidazolium (C(n)mim(+), the alkyl-chain lengths n of 4, 6, 8, 10, and 12) bis(trifluoromethanesulfonyl)amide (TFSA(-)), and methanol were investigated using small-angle neutron scattering (SANS), attenuated total reflectance infrared (ATR-IR), and NMR techniques. SANS measurements revealed that C(n)mim(+)TFSA(-) is heterogeneously mixed with methanol in the methanol mole fraction range of 0.8 ≤x(CD(3)OD) ≤ 0.995. The heterogeneity of the C(n)mim(+)TFSA(-)-methanol solutions, except for C(4)mim(+)TFSA(-), is most enhanced at x(CD(3)OD) ≈ 0.97 over the entire mole fraction range. Thus, the mole fraction at the maximum heterogeneity of the solutions is independent of the alkyl-chain length. In contrast, the magnitude of the maximum heterogeneity of the solutions is larger in the order of the alkyl-chain length from n = 4 to 12. ATR-IR and NMR measurements showed that methanol molecules gradually form hydrogen bonds among them in the solutions with increasing x(CH(3)OH). In particular, the hydrogen-bonds among methanol molecules are conspicuously evolved in the solutions above x(CH(3)OH) ≈ 0.8. The increase in the concentration of the hydrogen-bonded methanol with increasing x(CH(3)OH) does not significantly depend on the alkyl-chain length. According to these results, we concluded that the heterogeneity of C(n)mim(+)TFSA(-)-methanol solutions arises from polar domains composed of the imidazolium rings, TFSA(-), and methanol clusters and nonpolar domains formed by interaction among the alkyl chains of the imidazolium cations.