Neuro and hepatic toxicological profile of (S)-2,4-diaminobutanoic acid in embryonic, adolescent and adult zebrafish

(S)-2,4-Diaminobutanoic acid (DABA) is a noncanonical amino acid often co-produced by cyanobacteria along with β-N-methylamino-l-alanine (BMAA) in algal blooms. Although BMAA is a well-established neurotoxin, the toxicity of DABA remains unclear. As part of our development of biocompatible materials, we wish to make use of DABA as both a building block and as the end-product of enzymatically-induced depolymerization; however, if it is toxic at very low concentrations, this would not be possible. We examined the toxicity of DABA using both in vivo embryonic and adult zebrafish models. At higher sub-lethal concentrations (700 µM), the fish demonstrated early signs of cardiotoxicity. Adolescent zebrafish were able to tolerate a higher concentration. Post-mortem histological analysis of juvenile zebrafish showed no liver or brain abnormalities associated with hepato- or neurotoxicity. Combined, these results show that DABA exhibits no overt toxicity at concentrations (100-300 µM) within an order of magnitude of those envisioned for its application. This study further highlights the low-cost and ease of using zebrafish as an early-stage toxicological screening tool

Strategies for the hyperpolarization of acetonitrile and related Ligands by SABRE

(Chemical Equation Presented) We report on a strategy for using SABRE (signal amplification by reversible exchange) for polarizing 1H and 13C nuclei of weakly interacting ligands which possess biologically relevant and nonaromatic motifs. We first demonstrate this via the polarization of acetonitrile, using Ir(IMes)(COD)Cl as the catalyst precursor, and confirm that the route to hyperpolarization transfer is via the J-coupling network. We extend this work to the polarization of propionitrile, benzylnitrile, benzonitrile, and trans-3-hexenedinitrile in order to assess its generality. In the 1H NMR spectrum, the signal for acetonitrile is enhanced 8-fold over its thermal counterpart when [Ir(H)2(IMes)(MeCN)3]+ is the catalyst. Upon addition of pyridine or pyridine-d5, the active catalyst changes to [Ir(H)2(IMes)- (py)2(MeCN)]+ and the resulting acetonitrile 1H signal enhancement increases to 20- and 60-fold, respectively. In 13C NMR studies, polarization transfers optimally to the quaternary 13C nucleus of MeCN while the methyl 13C is hardly polarized. Transfer to 13C is shown to occur first via the 1H - 1H coupling between the hydrides and the methyl protons and then via either the 2J or 1J couplings to the respective 13Cs, of which the 2J route is more efficient. These experimental results are rationalized through a theoretical treatment which shows excellent agreement with experiment. In the case of MeCN, longitudinal two-spin orders between pairs of 1H nuclei in the three-spin methyl group are created. Two-spin order states, between the 1H and 13C nuclei, are also created, and their existence is confirmed for Me13CN in both the 1H and 13C NMR spectra using the Only Parahydrogen Spectroscopy protocol

Terrestrial selenium distribution in China is potentially linked to monsoonal climate

The prevalence of terrestrial environments low in the essential trace element selenium (Se) results in large-scale Se deficiency worldwide. However, the underlying processes leading to Se-depleted environments have remained elusive. Here we show that over the last 6.8 million years (Ma) climatic factors have played a key role in the Se distribution in loess-paleosol sequences in the Chinese Loess Plateau (CLP), which lies in a severely Se-depleted region with a history of Se deficiency-related diseases. We use a combination of geochemical and paleoclimate data to demonstrate that during interglacial periods between 2.30 and 0.16 Ma, variations in the Se concentration in the CLP are potentially related to variability in Se input via East Asian monsoon-derived precipitation. Our results identify precipitation as an important controlling factor of Se distribution in monsoonal China. We suggest that atmospheric Se inputs via precipitation could also play an important role in other regions worldwide.</p