Electrontransfer through DNA and metal-containing DNA

DNA is currently explored as a new material for functional, molecular nano-architectures. In this respect, one major question is to transform DNA into a conducting material which has the potential for self-assembly into electronically active networks. The article covers recent insight into how DNA transports positive (holes) and negative (excess electrons) charges. It was found that holes move through DNA over significant distances using a G- and to a lesser extent also A-based hopping mechanism. EPR studies and recent investigations with model systems show that excess electrons can also hop through the duplex. The second part of the article describes how DNA is currently modified, particularly coated with metals, in order to increase the conductivity.     

Interactive System for Similarity-Based Inspection and Assessment of the Well-Being of mHealth Users

Recent digitization technologies empower mHealth users to conveniently record their Ecological Momentary Assessments (EMA) through web applications, smartphones, and wearable devices. These recordings can help clinicians understand how the users’ condition changes, but appropriate learning and visualization mechanisms are required for this purpose. We propose a web-based visual analytics tool, which processes clinical data as well as EMAs that were recorded through a mHealth application. The goals we pursue are (1) to predict the condition of the user in the near and the far future, while also identifying the clinical data that mostly contribute to EMA predictions, (2) to identify users with outlier EMA, and (3) to show to what extent the EMAs of a user are in line with or diverge from those users similar to him/her. We report our findings based on a pilot study on patient empowerment, involving tinnitus patients who recorded EMAs with the mHealth app TinnitusTips. To validate our method, we also derived synthetic data from the same pilot study. Based on this setting, results for different use cases are reported.     

Salicylate metal-binding isosteres as fragments for metalloenzyme inhibition

Metalloenzyme inhibitors typically share a common need to possess a metal-binding pharmacophore (MBP) for binding the active site metal ions. However, MBPs can suffer from physicochemical liabilities, impeding the pharmacological properties and drug-likeliness of inhibitors. To circumvent this, problematic features of the MBP can be identified and exchanged with isosteric replacements. Herein, the carboxylic and hydroxyl group of the salicylic acid MBP were replaced and a total of 27 salicylate metal-binding isosteres (MBIs) synthesized. Of these 27 MBIs, at least 12 represent previously unreported compounds, and the metal-binding abilities of >20 of the MBIs have not been previously reported. These salicylate MBIs were examined for their metal-binding features in model complexes, physicochemical properties, and biological activity. It was observed that salicylate MBIs can demonstrate a range of attractive physicochemical properties and bind to the metal in a variety of expected and unexpected binding modes. The biological activity of these novel MBIs was evaluated by measuring inhibition against two Zn²⁺-dependent metalloenzymes, human glyoxalase 1 (GLO1) and matrix metalloproteinase 3 (MMP-3), as well as a dinuclear Mn²⁺-dependent metalloenzyme, influenza H1N1 N-terminal endonuclease (PA_N). It was observed that salicylate MBIs could maintain or improve enzyme inhibition and selectivity. To probe salicylate MBIs as fragments for fragment-based drug discovery (FBDD), an MBI that showed good inhibitory activity against GLO1 was derivatized and a rudimentary structure–activity relationship was developed. The resulting elaborated fragments showed GLO1 inhibition with low micromolar activity.

Metal-binding isosteres (MBIs) of salicylic acid have been developed for metalloenzyme drug development.     

Interactions between ions and free or immobilized ligands. Application of the competition method

Application of a competition method to determine affinities of ligands for ionic species in low polarity media is described. A soluble ligand, L, and a network-immobilized ligand, N, are allowed to interact with the counterion of an ionic chromophore A” according to the reaction NM⁺A⁻ + L → LM⁺A⁻ + N (K). K values were determined in toluene and in ether-type solvents for linear and macrocyclic polyethers and polyamines, as well as for other cation-complexing agents, by varying either N or L. In solvents such as dioxane, binding constants of M⁺A⁻ to N can be determined directly. Combined with K values they yield the complex formation constant, K_L, of the reaction M⁺A⁻ + L → LM+A⁻.