scholarly journals Experiment stands corrected: accurate prediction of the aqueous pKa values of sulfonamide drugs using equilibrium bond lengths

2019 ◽  
Vol 10 (25) ◽  
pp. 6368-6381 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Paul L. A. Popelier
Keyword(s):  
Accurate Prediction ◽  
Strongly Correlated ◽  
Pka Values ◽  
Bond Lengths ◽  
Linear Relationships ◽  
Aqueous Pka ◽  
First Time ◽  
Sulfonamide Group

We show here for the first time that strongly correlated linear relationships exist between equilibrium bond lengths of the sulfonamide group and aqueous pKa values.

Experiment Stands Corrected: Accurate Prediction of the Aqueous pKa Values of Sulfonamide Drugs Using Equilibrium Bond Lengths

2019 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Paul Popelier
Keyword(s):  
Strongly Correlated ◽  
Pka Values ◽  
Pka Prediction ◽  
Thermodynamic Cycles ◽  
Bond Lengths ◽  
Linear Relationships ◽  
Aqueous Pka ◽  
Experimental Values ◽  
First Time ◽  
Sulfonamide Group

We show here for the first time that strongly correlated linear relationships exist between equilibrium bond lengths of the sulfonamide group and aqueous pKa values. Models are constructed for three variants of the SO2NHR group: primary benzene sulfonamide derivatives (e.g. diuretic drugs furosemide and hydrochlorothiazide), N-phenyl substituted 4-amino-N-phenylbenzenesulfonamide analogues (e.g. the sulfa antibiotic sulfadiazine) and phenylsulfonylureas (e.g. insulin secretogogue, glimepiride). In the context of these compounds, we present solutions to some of the more complex challenges in pKa prediction: (i) prediction for multiprotic compounds, (ii) predicting macroscopic values for compounds that tautomerize, and (iii) quantum chemical pKa prediction for compounds with more than 50 atoms. Using bond lengths as a powerful descriptor of ionization feasibility, we also identify that literature values for drug compounds celecoxib, glimepiride and glipizide are inaccurate. Our newly measured experimental values match our initial predictions to within 0.26 pKa units, whereas previous values were found to deviate by up to 1.68 pKa units. For glimepiride, our corrected value denotes a percentage of ionization at intracellular pH, which is only now in excellent agreement with its known therapeutic efficacy. We propose that linear relationships between bond lengths and pKa should emerge for any set of congeners, thus providing a powerful method of pKa prediction obviating the need for thermodynamic cycles.

Experiment Stands Corrected: Accurate Prediction of the Aqueous pKa Values of Sulfonamide Drugs Using Equilibrium Bond Lengths

2019 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Paul Popelier
Keyword(s):  
Strongly Correlated ◽  
Pka Values ◽  
Pka Prediction ◽  
Thermodynamic Cycles ◽  
Bond Lengths ◽  
Linear Relationships ◽  
Aqueous Pka ◽  
Experimental Values ◽  
First Time ◽  
Sulfonamide Group

We show here for the first time that strongly correlated linear relationships exist between equilibrium bond lengths of the sulfonamide group and aqueous pKa values. Models are constructed for three variants of the SO2NHR group: primary benzene sulfonamide derivatives (e.g. diuretic drugs furosemide and hydrochlorothiazide), N-phenyl substituted 4-amino-N-phenylbenzenesulfonamide analogues (e.g. the sulfa antibiotic sulfadiazine) and phenylsulfonylureas (e.g. insulin secretogogue, glimepiride). In the context of these compounds, we present solutions to some of the more complex challenges in pKa prediction: (i) prediction for multiprotic compounds, (ii) predicting macroscopic values for compounds that tautomerize, and (iii) quantum chemical pKa prediction for compounds with more than 50 atoms. Using bond lengths as a powerful descriptor of ionization feasibility, we also identify that literature values for drug compounds celecoxib, glimepiride and glipizide are inaccurate. Our newly measured experimental values match our initial predictions to within 0.26 pKa units, whereas previous values were found to deviate by up to 1.68 pKa units. For glimepiride, our corrected value denotes a percentage of ionization at intracellular pH, which is only now in excellent agreement with its known therapeutic efficacy. We propose that linear relationships between bond lengths and pKa should emerge for any set of congeners, thus providing a powerful method of pKa prediction obviating the need for thermodynamic cycles.

scholarly journals The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths

2016 ◽  
Vol 56 (3) ◽  
pp. 471-483 ◽  
Author(s):  
Cate Anstöter ◽  
Beth A. Caine ◽  
Paul L. A. Popelier
Keyword(s):  
Phase Equilibrium ◽  
Gas Phase ◽  
Pka Values ◽  
Bond Lengths ◽  
Aqueous Pka

scholarly journals Delayed implantation in giant pandas: the first comprehensive empirical evidence

Reproduction ◽  
2009 ◽  
Vol 138 (6) ◽  
pp. 979-986 ◽  
Author(s):  
Hemin Zhang ◽  
Desheng Li ◽  
Chendong Wang ◽  
Vanessa Hull
Keyword(s):  
Reproductive Biology ◽  
Giant Panda ◽  
Reproductive Development ◽  
Mammary Glands ◽  
Strongly Correlated ◽  
Physiological Changes ◽  
Giant Pandas ◽  
Delayed Implantation ◽  
Infant Birth ◽  
First Time

Successful conservation of an endangered species relies on a good understanding of its reproductive biology, but there are large knowledge gaps. For example, many questions remain unanswered with regard to gestation and fetal development in the giant panda. We take advantage of a sample size that is unprecedented for this species (n=13) to explore patterns in reproductive development across individuals at the China Conservation and Research Center for the Giant Panda. We use ultrasound techniques on multiple giant pandas for the first time to empirically confirm what has long been suspected that pandas exhibit delayed implantation of the embryo. We also show that the duration of postfetal detection period is remarkably similar across individuals (16.85±1.34 days). Detection of fetus by ultrasound was strongly correlated to the peak in urinary progesterone (r=0.96, t=8.48, d.f.=8, P=0.0001) and swelling in the mammary glands (r=0.79, t=3.61, d.f.=8, P=0.007) and vulva (r=0.91, t=6.40, d.f.=8, P=0.0002) of adult females. When controlling for both the duration of the total gestation period and the postfetal detection period, infant birth weight was only significantly predicted by the latter (β=11.25, s.e.m.=4.98, t=2.26, P=0.05), suggesting that delayed implantation increases flexibility in the timing of birth but is not important in dictating infant growth. This study informs reproductive biology by exploring the little-studied phenomenon of delayed implantation in relationship to physiological changes in pregnant giant panda females.

Information-based analysis of the coupling between brain and heart reactions to olfactory stimulation

2021 ◽  
pp. 1-11
Author(s):  
Najmeh Pakniyat ◽  
Mohammad Hossein Babini ◽  
Vladimir V. Kulish ◽  
Hamidreza Namazi
Keyword(s):  
Time Series ◽  
Biomedical Science ◽  
Strongly Correlated ◽  
Eeg Signals ◽  
Ecg Signals ◽  
Olfactory Stimuli ◽  
Electrocardiogram Ecg ◽  
First Time ◽  
Electroencephalogram Eeg ◽  
The Brain

BACKGROUND: Analysis of the heart activity is one of the important areas of research in biomedical science and engineering. For this purpose, scientists analyze the activity of the heart in various conditions. Since the brain controls the heart’s activity, a relationship should exist among their activities. OBJECTIVE: In this research, for the first time the coupling between heart and brain activities was analyzed by information-based analysis. METHODS: Considering Shannon entropy as the indicator of the information of a system, we recorded electroencephalogram (EEG) and electrocardiogram (ECG) signals of 13 participants (7 M, 6 F, 18–22 years old) in different external stimulations (using pineapple, banana, vanilla, and lemon flavors as olfactory stimuli) and evaluated how the information of EEG signals and R-R time series (as heart rate variability (HRV)) are linked. RESULTS: The results indicate that the changes in the information of the R-R time series and EEG signals are strongly correlated (ρ=-0.9566). CONCLUSION: We conclude that heart and brain activities are related.

scholarly journals Mori Ramulus (Chin.Ph.)—the Dried Twigs of Morus alba L./Part 1: Discovery of Two Novel Coumarin Glycosides from the Anti-Hyperuricemic Ethanol Extract

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 629
Author(s):  
Jianbiao Yao ◽  
Houhong He ◽  
Jin Xue ◽  
Jianfang Wang ◽  
Huihui Jin ◽  
...  
Keyword(s):  
Natural Products ◽  
Ethanol Extract ◽  
Accurate Method ◽  
Morus Alba ◽  
Strongly Correlated ◽  
Bioactive Constituents ◽  
Antiplatelet Aggregation ◽  
Pharmacologically Active ◽  
First Time ◽  
Tof Ms

In Traditional Chinese Medicine (TCM), Mori ramulus (Chin.Ph.)—the dried twigs of Morus alba L.—is extensively used as an antirheumatic agent and also finds additional use in asthma therapy. As a pathological high xanthine oxidase (XO, EC 1.1.3.22) activity is strongly correlated to hyperuricemy and gout, standard anti-hyperuremic therapy typically involves XO inhibitors like allopurinol, which often cause adverse effects by inhibiting other enzymes involved in purine metabolism. Mori ramulus may therefore be a promissing source for the development of new antirheumatic therapeutics with less side effects. Coumarins, one of the dominant groups of bioactive constituents of M. alba, have been demonstrated to possess anti-inflammatory, antiplatelet aggregation, antitumor, and acetylcholinesterase (AChE) inhibitory activities. The combination of HPLC (DAD) and Q-TOF technique could give excellent separating and good structural characterization abilities which make it suitable to analyze complex multi-herbal extracts in TCM. The aim of this study was to develop a HPLC (DAD)/ESI-Q-TOF-MS/MS method for the identification and profiling of pharmacologically active coumarin glycosides in Mori ramulus refined extracts for used in TCM. This HPLC (DAD)/ESI-Q-TOF-MS/MS method provided a rapid and accurate method for identification of coumarin glycosides—including new natural products described here for the first time—in the crude extract of M. alba L. In the course of this project, two novel natural products moriramulosid A (umbelliferone-6-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside) and moriramulosid B (6-[[6-O-(6-deoxy-α-l-mannopyranosyl)-β-d-glucopyranosyl]oxy]-2H-1-benzopyran-1-one) were newly discovered and the known natural product Scopolin was identified in M. alba L. for the first time.

scholarly journals The effect of stellar activity on the spectroscopic stellar parameters of the young solar twin HIP 36515

2019 ◽  
Vol 490 (1) ◽  
pp. L86-L90 ◽  
Author(s):  
Jhon Yana Galarza ◽  
Jorge Meléndez ◽  
Diego Lorenzo-Oliveira ◽  
Adriana Valio ◽  
Henrique Reggiani ◽  
...  
Keyword(s):  
Effective Temperature ◽  
Signal To Noise Ratio ◽  
Activity Cycle ◽  
Magnetic Activity ◽  
Resolving Power ◽  
Strongly Correlated ◽  
Chemical Abundances ◽  
Stellar Activity ◽  
Time Variations ◽  
First Time

ABSTRACT Spectroscopic equilibrium allows us to obtain precise stellar parameters in Sun-like stars. It relies on the assumption of the iron excitation and ionization equilibrium. However, several works suggest that magnetic activity may affect chemical abundances of young active stars, calling into question the validity of this widely used method. We have tested, for the first time, variations in stellar parameters and chemical abundances for the young solar twin HIP 36515 (∼0.4 Gyr), along its activity cycle. This star has stellar parameters very well established in the literature and we estimated its activity cycle in ∼6 yr. Using HARPS spectra with high resolving power (115 000) and signal-to-noise ratio (∼270), the stellar parameters of six different epochs in the cycle were estimated. We found that the stellar activity is strongly correlated with the effective temperature, metallicity, and microturbulence velocity. The possibility of changes in the Li i 6707.8 Å line due to flares and star-spots was also investigated. Although the core of the line profile shows some variations with the stellar cycle, it is compensated by changes in the effective temperature, resulting in a non-variation of the Li abundance.

An Assessment of Theoretical Protocols for Calculation of the pKa Values of the Prototype Imidazolium Cation

2004 ◽  
Vol 57 (12) ◽  
pp. 1205 ◽  
Author(s):  
Alison M. Magill ◽  
Brian F. Yates
Keyword(s):  
Excellent Agreement ◽  
Basis Set ◽  
Hydrogen Atoms ◽  
Imidazolium Cation ◽  
Pka Values ◽  
Experimental Estimate ◽  
Pka Calculation ◽  
Complete Basis Set ◽  
Aqueous Pka ◽  
Experimental Values

The highly accurate complete basis set method CBS-QB3 has been used in conjunction with the conductor-like polarized continuum (CPCM) method to predict the aqueous pKa values for the three different hydrogen atoms in the imidazolium cation. Excellent agreement was obtained with the available experimental values. The pKa for the deprotonation of imidazole was also calculated and found to be quite different from the experimental estimate. The protocol for the pKa calculation was carefully analyzed and some recommendations made about the choice of levels of theory.

Individualism/Collectivism and Organizational Citizenship Behavior: An Integrative Framework

2012 ◽  
Vol 40 (10) ◽  
pp. 1633-1643 ◽  
Author(s):  
Marcia A. Finkelstein
Keyword(s):  
Organizational Citizenship ◽  
Organizational Citizenship Behavior ◽  
Well Being ◽  
Role Identity ◽  
Citizenship Behavior ◽  
Strongly Correlated ◽  
Integrative Framework ◽  
Individualism And Collectivism ◽  
Per Se ◽  
First Time

In this study individualism and collectivism are, for the first time, incorporated into a conceptual model of organizational citizenship behavior (OCB). I asked whether individualism and collectivism show systematic differences in their relationships with OCB, its motives, and the development of a citizen role identity. Collectivism most strongly correlated with OCB motivated by concern for coworkers. A concept of self as one who helps others at work was also associated with collectivism. Individualism was associated more with a commitment to the well-being of the institution per se rather than to its employees. Individualism and collectivism were related positively, suggesting that these seemingly opposing attributes are complementary; which of these traits predominates may depend on which citizenship behavior is needed at a given time. Overall, the findings suggest that it is not in amount of citizenship that individualists and collectivists differ, but in why they serve and how they perceive the experience.

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