UV-adVISor: Attention-Based Recurrent Neural Networks to Predict UV-Vis Spectra.

Ultraviolet-visible (UV-Vis) absorption spectra are routinely collected as part of high-performance liquid chromatography (HPLC) analysis systems and can be used to identify chemical reaction products by comparison to the reference spectra. Here, we present UV-adVISor as a new computational tool for predicting the UV-Vis spectra from a molecule's structure alone. UV-Vis prediction was approached as a sequence-to-sequence problem. We utilized Long-Short Term Memory and attention-based neural networks with Extended Connectivity Fingerprint Diameter 6 or molecule SMILES to generate predictive models for the UV spectra. We have produced two spectrum datasets (dataset I, N = 949, and dataset II, N = 2222) using different compound collections and spectrum acquisition methods to train, validate, and test our models. We evaluated the prediction accuracy of the complete spectra by the correspondence of wavelengths of absorbance maxima and with a series of statistical measures (the best test set median model parameters are in parentheses for model II), including RMSE (0.064), R2 (0.71), and dynamic time warping (DTW, 0.194) of the entire spectrum curve. Scrambling molecule structures with the experimental spectra during training resulted in a degraded R2, confirming the utility of the approaches for prediction. UV-adVISor is able to provide fast and accurate predictions for libraries of compounds.

Dimethyl Itaconate Is Not Metabolized into Itaconate Intracellularly.

Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used [13C]itaconate and dimethyl [13C]itaconate (DMI) to probe itaconate metabolism, and find that [13C]DMI is not metabolized to itaconate. [13C]Itaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this study is to encourage the development of effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.

Synthesis of [15 N]-cholamine bromide hydrobromide.

[15 N]-Cholamine is an isotope tag for metabolomics research, because it possesses 2 important properties: an NMR active isotope and a permanent charge for MS sensitivity. Here, we present a scalable synthesis of [15 N]-cholamine.

A Platform for the Detection of Trypanosomes via Selective Small Molecule Recognition.

Trypanothione (TSH2), a metabolite unique to trypanosomal parasites, was evaluated as a potential biomarker for trypanosomal infection using fluorescence as the means of detection. Fluoroescein arsenical helix binder (FLASH) was prepared and used to detect TSH2. Since it has low background fluorescence and forms a highly emissive complex with TSH2, it can be used to detect low micromolar concentrations of TSH2 in serum. The large dynamic range of FLASH and its selectivity for detection of the dithiol metabolite indicate that arsenical probes may offer a promising new platform for the diagnosis of trypanosomal infection.