High Pressure Polymerization of 2,6-Diethynylpyridine

Pressure induced polymerization (PIP) of unsaturated molecules like aromatics is highly focused on its production of novel carbon materials like diamond nanothread and graphane. However, the high stability of the aromatic molecules results in a high polymerization pressure at room temperature. To reduce the reaction pressure of the aromatic ring, here we introduced conjugated alkynyl, investigated the PIP of 2,6-diethynylpyridine (2,6-DEP) up to 30.7 GPa, and successfully obtained one-dimensional (1-D) ordered polymers below 10 GPa. In situ Raman and IR spectra show that the alkynyl starts to react at 4–5 GPa. At 5.4 GPa, the critical crystal structure of 2,6-DEP was investigated by in situ X-ray diffraction, and the shortest intermolecular distance was determined as 2.90 Å, between the pyridine ring. The product recovered from 10 GPa shows clearly a 1-D structure via transmission electron microscopy (TEM), and strong diffractions at d = 7.5 and 5.2 Å, corresponding to the interplane distance of the stacked 1-D polymer. Theoretical simulations show that the reaction starts between the alkynyl groups, after which the aromatic rings are drawn close to each other and react. Combining the predicted reaction and the experimental result, we concluded possible models of the product. Our study shows that alkynyl is a good initiator for reducing the polymerization pressure of the aromatics and therefore allows the synthesis of ordered 1-D carbon materials in large scale

S1 Checklist -

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients.Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).</div

Study procedures.

There is no Day 0 in the study. IMP, investigational medical product; PK, pharmacokinetic.</p

Pharmacokinetic parameters of mesalazine after the first, 5^th and 7^th dose of 1 g/100 mL mesalazine enema in healthy Chinese subjects.

Pharmacokinetic parameters of mesalazine after the first, 5th and 7th dose of 1 g/100 mL mesalazine enema in healthy Chinese subjects.</p

Summary of adverse events reported in 11 healthy Chinese subjects.

Summary of adverse events reported in 11 healthy Chinese subjects.</p

S1 File -

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients.Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).</div

Urinary excretion parameters of mesalazine and N-acetyl mesalazine within 24 h after the 7^th dose administration of 1 g/100 mL mesalazine enema in healthy Chinese subjects.

Urinary excretion parameters of mesalazine and N-acetyl mesalazine within 24 h after the 7th dose administration of 1 g/100 mL mesalazine enema in healthy Chinese subjects.</p

CONSORT flowchart showing the disposition of subjects.

CONSORT flowchart showing the disposition of subjects.</p

Mean plasma mesalazine concentration-time profiles (linear and semi-logarithmic) after the first, 5^th and 7^th dose administration of 1 g/100 mL mesalazine enema in healthy Chinese subjects.

(A) Linear concentration plot; (B) Zoom in view of panel A from 0 to 8 hours; (C) Semi-logarithmic concentration plot; (D) Zoom in view of panel C from 0 to 8 hours. Each plot represents the mean (standard deviation) concentration of mesalazine.</p

Pressure Gradient Squeezing Hydrogen out of MnOOH: Thermodynamics and Electrochemistry

Pressure of gigapascal (GPa) is a robust force for driving phase transitions and chemical reactions with negative volume change and is intensely used for promoting combination/addition reactions. Here, we find that the pressure gradient between the high-pressure region and the ambient-pressure environment in a diamond anvil cell is an even stronger force to drive decomposition/elimination reactions. A pressure difference of tens of GPa can “push” hydrogen out from its compounds in the high-pressure region to the environment. More importantly, in transition metal hydroxides such as MnOOH, the protons and electrons of hydrogen can even be separated via different conductors, pushed out by the high pressure, and recombine outside under ambient conditions, producing continuous current. A pressure-gradient-driven battery is hence proposed. Our investigation demonstrated that a pressure gradient is a special and powerful force to drive decomposition and electrochemical reactions