9 research outputs found
Thiosquaramides: pH switchable anion transporters
The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquar-amides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH
pH switchable anion transport by an oxothiosquaramide
An oxothiosquaramide was shown to bind to chloride through
hydrogen bonding interactions in DMSO and found to exhibit pH
switchable choride transport across phospholipid bilayers via an
antiport transport mechanism
Dataset for pH switchable anion transport by an oxothiosquaramide
NMR titration data, pKa determination data, anion transport data, chloride binding data</span
Dataset for pH-Regulated Nonelectrogenic Anion Transport by Phenylthiosemicarbazones
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pH-Regulated Nonelectrogenic Anion Transport by Phenylthiosemicarbazones
Gated ion transport across biological
membranes is an intrinsic
process regulated by protein channels. Synthetic anion carriers (anionophores)
have potential applications in biological research; however, previously
reported examples are mostly nonspecific, capable of mediating both
electrogenic and electroneutral (nonelectrogenic) transport processes.
Here we show the transmembrane Cl<sup>–</sup> transport studies
of synthetic phenylthiosemicarbazones mimicking the function of acid-sensing
(proton-gated) ion channels. These anionophores have remarkable pH-switchable
transport properties with up to 640-fold increase in transport efficacy
on going from pH 7.2 to 4.0. This “gated” process is
triggered by protonation of the imino nitrogen and concomitant conformational
change of the anion-binding thiourea moiety from anti to syn. By using
a combination of two cationophore-coupled transport assays, with either
monensin or valinomycin, we have elucidated the fundamental transport
mechanism of phenylthiosemicarbazones which is shown to be nonelectrogenic,
inseparable H<sup>+</sup>/Cl<sup>–</sup> cotransport. This
study demonstrates the first examples of pH-switchable nonelectrogenic
anion transporters
Metabolic syndrome is associated with similar long-term prognosis in non-obese and obese patients. An analysis of 45 615 patients from the nationwide LIPIDOGRAM 2004-2015 cohort studies
Aims We aimed to evaluate the association between metabolic syndrome (MetS) and long-term all-cause mortality. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. MetS was diagnosed based on the National Cholesterol Education Program, Adult Treatment Panel III (NCEP/ATP III) and Joint Interim Statement (JIS) criteria. The cohort was divided into four groups: non-obese patients without MetS, obese patients without MetS, non-obese patients with MetS and obese patients with MetS. Differences in all-cause mortality was analyzed using Kaplan-Meier and Cox regression analyses. Results 45,615 participants were enrolled (mean age 56.3, standard deviation: 11.8 years; 61.7% female). MetS was diagnosed in 14,202 (31%) by NCEP/ATP III criteria, and 17,216 (37.7%) by JIS criteria. Follow-up was available for 44,620 (97.8%, median duration 15.3 years) patients. MetS was associated with increased mortality risk among the obese (hazard ratio, HR: 1.88 [95% CI, 1.79-1.99] and HR: 1.93 [95% CI 1.82-2.04], according to NCEP/ATP III and JIS criteria, respectively) and non-obese individuals (HR: 2.11 [95% CI 1.85-2.40] and 1.7 [95% CI, 1.56-1.85] according to NCEP/ATP III and JIS criteria respectively). Obese patients without MetS had a higher mortality risk than non-obese patients without MetS (HR: 1.16 [95% CI 1.10-1.23] and HR: 1.22 [95%CI 1.15-1.30], respectively in subgroups with NCEP/ATP III and JIS criteria applied). Conclusions MetS is associated with increased all-cause mortality risk in non-obese and obese patients. In patients without MetS obesity remains significantly associated with mortality. The concept of metabolically healthy obesity should be revised