Palladium-Catalyzed Regioselective C-H Functionalization of Arenes Substituted by Two N-Heterocycles and Application in Late-Stage Functionalization.

Reported herein is a Pd-catalyzed regioselective C-H activation method that is used for C-H deuteration, carbonylation, halogenation, and oxidation of arene substrates substituted by two N-heterocycles. When conducted in acetic acid (AcOH), these reactions occur at the five-membered palladacycle sites, whereas they switch to the six-membered palladacycle sites in trifluoroacetic acid (TFA). This controllable regioselective C-H activation is applied for late-stage functionalization of bioactive molecules. A mechanism study indicated that the regioselectivity is achieved by Brönsted acid-Lewis base interactions and electronic effects (in TFA) and the different kinetic stabilities of palladacycle intermediates (in AcOH).

Vitamin D, parathyroid hormone, and serum lipid profiles in a middle-aged and elderly Chinese population.

OBJECTIVES: To explore the associations of serum vitamin D and parathyroid hormone (PTH) levels with serum lipid profiles and the risk of hyperlipidemia in a middle-aged and elderly population. METHODS: A population-based cross-sectional study was conducted in the spring of 2012 among 1,203 Chinese participants, aged 52 to 101 years. 25-Hydroxyvitamin D [25(OH)D] was measured by chemiluminescence assay. (PTH) levels were measured with an electrochemiluminescence immunoassay (ECLIA) method. RESULTS: A total of 1,203 participants, including 526 women (43.7%), were evaluated in 2012. The median concentrations of serum 25(OH)D and PTH for the entire group were 17.3 ng/mL and 38.3 pg/mL, respectively. Serum 25(OH)D and PTH levels were not independently associated with serum total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels in a multivariate adjusted linear regression analysis of 1,027 participants not receiving antihyperlipidemic treatment (P>.05). In logistic regression analyses, serum 25(OH)D and PTH levels were not associated with a risk of hyperlipidemia after adjustment for age, sex, heavy drinking, smoking, diabetes, obesity, family history of hyperlipidemia, body mass index (BMI), physical activity, glomerular filtration rate (GFR), fasting glucose, high-sensitivity C-reactive protein (hsCRP), calcium, and hemoglobin. CONCLUSIONS: Serum 25(OH)D and PTH levels are not independently associated with serum lipid levels or an increased risk of hyperlipidemia in a middle-aged and elderly Chinese population.

Relation of low vitamin D to nonvalvular persistent atrial fibrillation in Chinese patients.

BACKGROUND: Low vitamin D status has been associated with increased risk of cardiovascular disease. Atrial fibrillation (AF) is the most common cardiac arrhythmia. We evaluated the association between low vitamin D and AF. METHODS: We analyzed data from 162 Chinese patients with nonvalvular persistent AF and no other cardiovascular disease whose serum 25-hydroxyvitamin D [25(OH)D] levels were measured in our hospital (AF group). Healthy subjects without AF who underwent health screening at our hospital served as controls (non-AF group, n = 160). 25(OH)D was measured by chemiluminescence assay. RESULTS: The serum 25(OH)D level was significantly lower in the AF group than in the non-AF group (18.5 ± 10.3 vs 21.4 ± 10.7 ng/mL, P < 0.05). The high-sensitivity C-reactive protein (hsCRP) level was significantly higher in the AF group than in the non-AF group (0.35 ± 0.19 vs 0.2 ± 0.17 mg/dL, P < 0.01). The average left atrial diameter was significantly larger in the AF group than in the non-AF group (P < 0.01). The serum 25(OH)D level showed a negative correlation with left atrial diameter, hsCRP level, and pulmonary artery systolic pressure. Logistic regression analysis identified that 25(OH)D was related to AF. Patients whose vitamin D levels were in the lowest 25(OH)D category (<20 ng/mL) were more often in the AF group, with their incidence about twofold higher than those in the highest 25(OH)D category (>30 ng/mL). CONCLUSIONS: Low vitamin D levels are associated with AF. It may be involved in its development.

The effects of low vitamin D on coronary artery disease.

PURPOSE: Coronary Artery Disease (CAD) remains a major cause of morbidity and mortality in the world. Low vitamin D status has been shown to be associated with increased risk of developing cardiovascular disease, hypertension and obesity. We planned to research the association between low vitamin D status and the severity of CAD. PROCEDURES: A total of 348 consecutive patients undergoing coronary angiography for evaluation of CAD were included in this study. 25-Hydroxyvitamin D [25(OH)D] was measured by chemiluminescence assay. CAD severity was assessed by using the SYNTAX scores. The data presented are the mean levels/values and standard deviation. FINDINGS: The serum 25(OH)D level of CAD patients was 18.2 ± 10.6 ng/ml. The SYNTAX scores were 27.8 ± 8.5. In a multivariate linear regression analysis (adjusted for age, high-sensitivity C-reactive protein, SYNTAX score, parathyroid hormone, body mass index, haemoglobin and creatinine), the serum 25(OH)D level showed a negative correlation with SYNTAX score and high-sensitivity C-reactive protein (hsCRP) level. Logistic regression analysis identified 25(OH)D as an independent factor related to high SYNTAX scores. Patients whose vitamin D levels were in the lowest 25(OH)D category (<20 ng/ml) were more often in the high SYNTAX scores group, with their incidence about two-fold higher than those in the highest 25(OH)D category (>30 ng/ml). CONCLUSION: Low vitamin D is associated with the severity of coronary artery stenosis.

Effects of Statin on Arrhythmia and Heart Rate Variability in Healthy Persons With 48-Hour Sleep Deprivation.

BACKGROUND: It has been reported that sleep deprivation is associated with cardiac autonomic disorder, inflammation, and oxidative stress. Statins have significant cardiovascular protective effects in patients with cardiovascular disease. This study aimed to investigate the protective effect of statins on arrhythmia and heart rate variability in young healthy persons after 48-hour sleep deprivation. METHODS AND RESULTS: This study enrolled 72 young healthy participants aged 26.5±3.5 years. All participants received 48-hour continuous ambulatory electrocardiogram monitoring. Arrhythmia, time, and frequency domain parameters were analyzed for all participants. The primary end point, low/high frequency ratio, was significantly lower in the statin group than in the control group (2.48±1.12 versus 3.02±1.23, P<0.001). After 48-hour sleep deprivation, low frequency-the frequency of premature atrial complexes and premature ventricular complexes-was significantly decreased in the statin group compared with the control group (P<0.05). There was also a significant increase in high frequency in the statin group compared with the control group (P<0.05). There was a significant decrease in serum high-sensitivity C-reactive protein and malondialdehyde levels after 48-hour sleep deprivation in the statin group compared with the control group (P<0.05). CONCLUSIONS: Statin use might be associated with improvement in arrhythmia and heart rate variability in healthy persons with 48-hour sleep deprivation. This finding should be confirmed by larger scale trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02496962.

Effects of vitamin D on plasma lipid profiles in statin-treated patients with hypercholesterolemia: A randomized placebo-controlled trial.

BACKGROUND & AIMS: Lipid abnormalities are regarded as a risk factor for cardiovascular disease. Low vitamin D status has been shown to be associated with hyperlipidemia. We planned to research the effects of vitamin D supplementation as an adjuvant therapy for patients with hypercholesterolemia. METHODS: Patients with hypercholesterolemia were enrolled in this single-center, double-blind, placebo-controlled trial in Beijing (39°54' N). Fifty-six patients were randomly assigned to receive vitamin D (n = 28, 2000 IU/d) or a placebo (n = 28) as an add-on to statin, by the method of permutated block randomization. Serum lipid levels were evaluated at baseline, 1, 3 and 6 months. RESULTS: Vitamin D supplementation resulted in increased serum 25-hydroxyvitamin D concentrations compared with placebo (+16.3 ± 11.4 compared with +2.4 ± 7.1 ng/ml; p < 0.001). At 6 months, the primary end point, a difference in the fall of serum total cholesterol levels between the vitamin D and placebo groups after 6 months of treatment was significant -22.1 mg/dl (95% CI -32.3; -12.2) (p < 0.001). The difference between the groups in the fall of serum triglyceride levels after 6 months of treatment was -28.2 mg/dl (95% CI -48.8; -8.4) (p < 0.001). In patients with 25-hydroxyvitamin D level<30 ng/ml at baseline (n = 43), the serum total cholesterol and triglyceride levels were reduced by -28.5 ± 11.9 mg/dl (p < 0.001) and -37.1 ± 19.5 mg/dl (p < 0.001), respectively. CONCLUSIONS: Vitamin D supplementation might improve serum lipid levels in statin-treated patients with hypercholesterolemia, it might be an adjuvant therapy for patients with hypercholesterolemia. Clinical Trials Registration Number - NCT02009787.

Vitamin D and nifedipine in the treatment of Chinese patients with grades I-II essential hypertension: a randomized placebo-controlled trial.

OBJECTIVES: Low vitamin D status has been shown to be associated with hypertension. We planned to research the effect of vitamin D and nifedipine in the treatment of patients with essential hypertension. METHODS: Patients with grades I-II essential hypertension were enrolled in this single-center, double-blind, placebo-controlled trial in Beijing. All patients received a conventional antihypertensive drug (nifedipine, 30 mg/d). One hundred and twenty-six patients were randomly assigned to receive vitamin D (n=63, 2000 IU/d) or a placebo (n=63) as an add-on to nifedipine, by the method of permutated block randomization. Ambulatory blood pressure monitoring was performed at baseline (month 0), at month 3 and at month 6. RESULTS: In vitamin D supplementation group, there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (19.4 ± 11.6 ng/ml) to 6 months (34.1 ± 12.2 ng/ml; p<0.001). At 6 months, the primary end points, a difference in the fall of 24-h mean blood pressure, between the groups was -6.2 mmHg (95% CI -11.2; -1.1) for systolic blood pressure (p<0.001) and -4.2 mmHg (95% CI -8.8; -0.3) for diastolic blood pressure (p<0.001) under intention to treat analysis. In patients with vitamin D <30 ng/ml at baseline (n=113), 24-h mean blood pressure decreased by 7.1/5.7 mmHg (p<0.001). Safety and tolerability were similar among the two groups. CONCLUSIONS: Vitamin D supplementation can reduce blood pressure in patients with hypertension, it can be an adjuvant therapy for patients with grades I-II essential hypertension. CLINICAL TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry, it is available in Website: http://www.chictr.org/cn/; REGISTRATION NUMBER: ChiCTR-ONC-13003840.

Synthesis, characterization and biological activity of ferrocene-based Schiff base ligands and their metal (II) complexes.

Metal (II) complexes derived from S-benzyl-N-(1-ferrocenyl-3-(4-methylbenzene)acrylketone) dithiocarbazate; HL(1), S-benzyl-N-(1-ferrocenyl-3-(4-chlorobenzene)acrylketone)dithiocarbazate; HL(2), all the compounds were characterized using various spectroscopic techniques. The molar conductance data revealed that the chelates were non-electrolytes. IR spectra showed that the Schiff bases were coordinated to the metal ions in a bidentate manner with N, S donor sites. The ligands and their metal complexes have been screened for in vitro antibacterial, antifungal properties. The result of these studies have revealed that zinc (II) complexes 6 and 13 of both the ligands and copper (II) complexes 9 of the HL(2) were observed to be the most active against all bacterial strains, antifungal activity was overall enhanced after complexation of the ligands.