Arthur Lindo Patterson, his function and element preferences in early crystal structures

In 1934, Arthur Lindo Patterson showed that a map of interatomic vectors is obtainable from measured X-ray diffraction data without phase information. Such maps were interpretable for simple crystal structures, but proliferation and overlapping of peaks caused confusion as the number of atoms increased. Since the peak height of a vector between two particular atoms is related to the product of their atomic numbers, a complicated structure could effectively be reduced to a simple one by including just a few heavy atoms (of high atomic number) since their interatomic vectors would stand out from the general clutter. Once located, these atoms provide approximate phases for Fourier syntheses that reveal the locations of additional atoms. Surveys of small-molecule structures in the Cambridge Structural Database during the periods 1936-1969, when Patterson methods were commonly used, and 1980-2013, dominated by direct methods, demonstrate large differences in the abundance of certain elements. The moderately heavy elements K, Rb, As and Br are the heaviest elements in the structure more than 3 times as often in the early period than in the recent period. Examples are given of three triumphs of the heavy atom method and two initial failures that had to be overcome

Caesium bis­(5-bromo­salicyl­aldehyde thio­semicarbazonato-κ3O,N,S)ferrate(III): supramolecular arrangement of low-spin FeIII complex anions mediated by Cs+ cations

The synthesis and crystal structure determination (at 293 K) of the title complex, Cs[Fe(C8H6BrN3OS)2], are reported. The compound is composed of two dianionic O,N,S-tridentate 5-bromo­salicyl­aldehyde thio­semicarbazonate(2-) ligands coord­inated to an FeIII cation, displaying a distorted octa­hedral geometry. The ligands are orientated in two perpendicular planes, with the O- and S-donor atoms in cis positions and the N-donor atoms in trans positions. The complex displays inter­molecular N-H...O and N-H...Br hydrogen bonds, creating R44(18) rings, which link the FeIII units in the a and b directions. The FeIII cation is in the low-spin state at 293 K

A concise synthesis of isoguanine 2’-deoxyriboside and its adenine-like triplex formation when incorporated into DNA

A concise synthesis of 2’-deoxyisoguanosine is achieved whereby 2,6-dichloropurine is glycosylated using the Hoffer sugar to give a pair of beta-configured nucleoside N9/N7 regioisomers that are aminated using methanolic ammonia with concomitant deprotection of the sugar. Following chromatographic separation, pure 2-chloro-2’-deoxyadenosine was isolated as a single isomer. Displacement of the C2 chlorine atom using sodium benzyloxide, followed by hydrogenolysis of the benzyl group, gives 2’-deoxyisoguanosine. Isoguanine was incorporated into DNA by solid supported synthesis using the suitably protected 2-allyloxy-2’-deoxyadenosine phosphoramidite with the allyl group being removed post-oligomerisation under Noyori conditions. DNA melting studies showed isoguanine to exhibit adenine-like triplex formation

Lars Vegard:key communicator and pioneer crystallographer

The Norwegian physicist Lars Vegard studied with William H. Bragg in Leeds and then with Wilhelm Wien in Würzburg. There, in 1912, he heard a lecture by Max Laue describing the first X-ray diffraction experiments and took accurate notes which he promptly sent to Bragg. Although now remembered mainly for his work on the physics of the aurora borealis, Vegard also did important pioneering work in three areas of crystallography. He derived chemical insight from a series of related crystal structures that he determined, Vegard's Law relates the unit-cell dimensions of mixed crystals to those of the pure components, and he determined some of the first crystal structures of gases solidified at cryogenic temperatures

Evaluation of analogues of furan-amidines as inhibitors of NQO2

Inhibitors of the enzyme NQO2 (NRH: quinone oxidoreductase 2) are of potential use in cancer chemotherapy and malaria. We have previously reported that non-symmetrical furan amidines are potent inhibitors of NQO2 and here novel analogues are evaluated. The furan ring has been changed to other heterocycles (imidazole, N-methylimidazole, oxazole, thiophene) and the amidine group has been replaced with imidate, reversed amidine, N-arylamide and amidoxime to probe NQO2 activity, improve solubility and decrease basicity of the lead furan amidine. All compounds were fully characterised spectroscopically and the structure of the unexpected product N-hydroxy-4-(5-methyl-4-phenylfuran-2-yl)benzamidine was established by X-ray crystallography. The analogues were evaluated for inhibition of NQO2, which showed lower activity than the lead furan amidine. The observed structure-activity relationship for the furan-amidine series with NQO2 was rationalized by preliminary molecular docking and binding mode analysis. In addition, the oxazole-amidine analogue inhibited the growth of Plasmodium falciparum with an IC50 value of 0.3 μM

Instrumental Perspectivism: Is AI Machine Learning Technology like NMR Spectroscopy?

The question, “Will science remain human?” expresses a worry that deep learning algorithms will replace scientists in making crucial judgments of classification and inference and that something crucial will be lost if that happens.  Ever since the introduction of telescopes and microscopes humans have relied on technologies to “extend” beyond human sensory perception in acquiring scientific knowledge.  In this paper I explore whether the ways in which new learning technologies “extend” beyond human cognitive aspects of science can be treated instrumentally. I will consider the norms for determining the reliability of a detection instrument, nuclear magnetic resonance spectroscopy, in predicting models of protein atomic structure. Do the same norms that apply in that case be used to judge the reliability of Artificial Intelligence deep learning algorithms