Alexander G. Ogston’s Centennial: Researcher of hyaluronic acid and other biopolymers

Alexander G. Ogston (1911–1996) investigated hyaluronic acid and other biopolymers with physico-chemical techniques. He investigated the behavior of macromolecules in solution in the presence of other macromolecules and described the exclusion effect, known also as molecular crowding. He determined that the molecular weight and many physico-chemical properties of biopolymers depend on their origins and the conditions of their preparation.     

Simultaneous determination of nanomole amounts of sulphur dioxide and hydrogen sulphide by flow injection analysis with on-line preconcentration by means of capillary denuder tubes

A simple and rapid method for trace determination of SO2 and H2S in gaseous samples by using a flow injection system with on line preconcentration on capillary denuder is described. The gaseous samples are led through a 0.4 M sulphamic acid solution, retaining nitrogen dioxide, ammonia and hydrogen chloride. The sulphur dioxide is collected from the carrier gas stream (250 cm3 min-1) as sulphuric acid in a capillary denuder tube coated with a thin layer of 0.01-0.03 M hydrogen peroxide solution of 0.05 mM sulphuric acid; hydrogen sulphide passes into a second tube coated with 0.075 mM sodium sulphide solution of 0.1 M aqueous sodium hydroxide. The films containing the sulphuric acid and the sodium sulphide, respectively, are eluted with the corresponding circulating absorbent streams and pass through the detectors. Sulphuric acid is detected by conductimetry and sulphide is determined spectrophotometrically at 230 nm. If nanoequivalent amounts of H2S are present in the sample containing a large concentration of SO2 (SO2/H2S concentration ratio > 20), the sulphur dioxide is filtered out of the sample gas stream by solid sodium hydrogen carbonate. A limit of detection of 3.5 micrograms m-3 is obtained.     

Evidence of Two Key Intermediates Contributing to the Selectivity of P450‐Biomimetic Oxidation of Sulfides to Sulfoxides and Sulfones

A mild process for the selective oxidation of sulfides is in great demand. Therefore, probing the mechanism underlying the biological oxidation of sulfides under ambient conditions may provide valuable insights for the development of such a reaction. Based on porphyrin models of P450 enzymes, evidence of two key intermediates, Int0 and Int1 , in this reaction is provided. Spectroscopic studies indicated the formation of a hydroperoxide‐iron(III) species ( Int0 ) upon addition of H₂O₂. This intermediate proved to be highly selective for sulfoxide production. By contrast, a defined porphyrin oxoiron(IV) cation radical ( Int1 ) directly reacted with sulfoxides, leading selectively to the corresponding sulfones. Interestingly, the available sulfoxides reversibly act as a new axial ligand for Int0 forming a more active species Int0 _SO. The amount of Int0 increased in the presence of alkyl, aryl, or aromatic sulfides, while Int1 formed in the absence of these sulfides. Thus, sulfoxides and sulfones would selectively form under conditions that favor the corresponding intermediates, which elucidate the biological oxidation pathway.     

Mechanisms of protein oligomerization: inhibitor of functional amyloids templates α-synuclein fibrillation

Small organic molecules that inhibit functional bacterial amyloid fibers, curli, are promising new antibiotics. Here we investigated the mechanism by which the ring-fused 2-pyridone FN075 inhibits fibrillation of the curli protein CsgA. Using a variety of biophysical techniques, we found that FN075 promotes CsgA to form off-pathway, non-amyloidogenic oligomeric species. In light of the generic properties of amyloids, we tested whether FN075 would also affect the fibrillation reaction of human α-synuclein, an amyloid-forming protein involved in Parkinson's disease. Surprisingly, FN075 stimulates α-synuclein amyloid fiber formation as measured by thioflavin T emission, electron microscopy (EM), and atomic force microscopy (AFM). NMR data on (15)N-labeled α-synuclein show that upon FN075 addition, α-synuclein oligomers with 7 nm radius form in which the C-terminal 40 residues remain disordered and solvent exposed. The polypeptides in these oligomers contain β-like secondary structure, and the oligomers are detectable by AFM, EM, and size-exclusion chromatography (SEC). Taken together, FN075 triggers oligomer formation of both proteins: in the case of CsgA, the oligomers do not proceed to fibers, whereas for α-synuclein, the oligomers are poised to rapidly form fibers. We conclude that there is a fine balance between small-molecule inhibition and templation that depends on protein chemistry.     

Jerzy Leszczynski—congratulations

Structural Chemistry - Jerzy Leszczynski is a much decorated chemist. He has been the Editor of Structural Chemistry for fifteen years and we join in the celebration of his 70th birthday.     

Squalyl Crown Ether Self‐Assembled Conjugates: An Example of Highly Selective Artificial K+ Channels

The natural KcsA K⁺ channel, one of the best‐characterized biological pore structures, conducts K⁺ cations at high rates while excluding Na⁺ cations. The KcsA K⁺ channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K⁺/Na⁺ selectivity has been achieved with artificial ion‐channel systems. However, simple artificial systems exhibiting K⁺/Na⁺ selectivity and mimicking the biofunctions of the KcsA K⁺ channel are unknown. Herein, an artificial ion channel formed by H‐bonded stacks of squalyl crown ethers, in which K⁺ conduction is highly preferred to Na⁺ conduction, is reported. The K⁺‐channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K⁺‐selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.     

Beta-Carotene Affects the Effects of Heme Oxygenase-1 in Isolated,Ischemic/Reperfused Rat Hearts: Potential Role of the Iron

Beta-carotene (BC) is a well-known antioxidant. However, increasing evidence shows that under severe oxidative conditions, BC can become pro-oxidant, an effect that may be enhanced in the presence of iron (II). In our earlier studies, we observed that despite increasing heme oxygenase-1 (HO-1) levels in the heart, the protective effects of BC have been lost when it was used at a high concentration. Since iron releases from heme as a consequence of HO-1 activity, we hypothesized that the application of an iron-chelator (IC) would reverse the lost cardiac protection associated with an elevated HO-1 level. Thus, in the present study, we investigated the effects of desferrioxiamine (DFO) in isolated, ischemic/reperfused rat hearts after long-term treatment with vehicle or high-dose (HD) BC. Vehicle or 150 mg/bw kg daily doses of BC were administered to the rats for 4 weeks, and then their hearts were removed and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). During the experiments, cardiac function was registered, and at the end of the REP period, infarct size (IS) and HO-1 expression were measured. The results show that DFO treatment alone during REP significantly ameliorated postischemic cardiac function and decreased IS, although HO-1 expression was not increased significantly. In hearts isolated from BC-treated rats, no cardioprotective effects, despite an elevated HO-1 level, were observed, while DFO administration after ISA resulted in a mild improvement in heart function and IS. Our results suggest that iron could have a role whether BC exerts antioxidant or pro-oxidant effects in ISA/REP-injured hearts.     

On the origins of isomorphous replacement in protein crystallography

Structural Chemistry -     

Walter B. Gratzer (1932–2021) – molecular scientist and science writer

Structural Chemistry - Walter Gratzer (1932–2021) arrived in England as a child refugee from Nazism, without speaking English, and became one of the most successful and influential science...