Targeting STING for cancer therapy: Activation of the STING (stimulator of interferon genes) protein by cyclic dinucleotide metabolites plays a critical role in antitumor immunity. The development of synthetic STING agonists is therefore being pursued as a strategy for cancer therapy, but the inherent instability of dinucleotides has limited current efforts. Pan et al. and Chin et al. identified stable STING agonists that act in a “closed” conformation similar to the natural STING ligand, cyclic guanosine monophosphate–adenosine monophosphate (see the Perspective by Gajewski and Higgs). The small molecules can be given orally—an advantage over previously developed STING agonists, which required intratumoral administration. After oral or systemic administration in mice, the agonists activated STING and diverse immune cell types to promote antitumor immunity. These studies represent progress toward clinically viable STING agonists for cancer immunotherapy. Science , this issue p. eaba6098 , p. 993 ; see also p. 921

Density functional theory (DFT) benchmark studies of ¹H and ¹³C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured ¹H and ¹³C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for ¹H and ¹³C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for ¹H and 0.5 to 2.9 for ¹³C. Maximum deviations were less than 0.5 and 6.5 ppm for ¹H and ¹³C, respectively.