Communications Chemistry最新文献

Peptide couplings have been a subject of investigation for over a century, with modern research seeking to discover new methodologies that minimize purification steps, minimize reagent expense, and/or decrease reaction times. Of the numerous coupling reagents available, sulfur(IV) fluorides have potential as they can effectively transform carboxylic acids to reactive intermediates, and the sulfite by-products can be removed through aqueous washes. Here we demonstrate the formation and capture of key acyl fluorosulfite intermediates for peptide couplings in 15 min total, without epimerization or column chromatography for purification. Dipeptides were obtained in 40-94% yields. This approach was expanded to longer chains through iterative couplings, with oligopeptides obtained in 24-57% yields, each within 2 days. Mechanistic studies indicate the reaction does not proceed through acyl fluoride intermediates, and instead involves nucleophilic catalysis. The mild conditions are tolerant of a wide range of protecting groups of canonical and non-canonical amino acids.

The F₁-ATPase molecular motor rotates subunit-γ in 120° power strokes within its ring of three catalytic sites separated by catalytic dwells for ATP hydrolysis and Pi release. By monitoring rotary position of subunit-γ in E. coli F₁ every 5 μs, we resolved Stage-1 catalytic dwell oscillations that extend from -13° to 13° centered at 0° consistent with F₁ structures containing transition state inhibitors, which decay by a first order process consistent with ATP hydrolysis. During Stage-2, 80% of the oscillations extend from 3° and 25° centered at 14°, while 20% are centered at 33° and can extend to 27°-44° comparable to the ATP binding position. Remarkably, in Stage-3 subunit-γ returns to 0° to end the catalytic dwell, which keeps the start of power strokes in phase for consecutive rotational events. These newly observed states fit with F₁ structures that were inconsistent with the canonical mechanism, and indicate that catalytic dwell oscillations must persist until the correct occupancy of substrates and products occurs at all three catalytic sites. When that condition is met, F₁ can proceed to the next power stroke. Understanding the basis of these catalytic dwell oscillations completes the F₁-ATPase rotary mechanism.

Nuclear Magnetic Resonance (NMR) spectroscopy is essential for revealing molecular structure, electronic environment, and dynamics. Accurate NMR shift prediction allows researchers to validate structures by comparing predicted and observed shifts. While Machine Learning (ML) has improved one-dimensional (1D) NMR shift prediction, predicting 2D NMR remains challenging due to limited annotated data. To address this, we introduce an unsupervised training framework for predicting cross-peaks in 2D NMR, specifically Heteronuclear Single Quantum Coherence (HSQC). Our approach pretrains an ML model on an annotated 1D dataset of ¹H and ¹³C shifts, then finetunes it in an unsupervised manner using unlabeled HSQC data, which simultaneously generates cross-peak annotations. Our model also adjusts for solvent effects. Evaluation on 479 expert-annotated HSQC spectra demonstrates our model's superiority over traditional methods (ChemDraw and Mestrenova), achieving Mean Absolute Errors (MAEs) of 2.05 ppm and 0.165 ppm for ¹³C shifts and ¹H shifts respectively. Our algorithmic annotations show a 95.21% concordance with experts' assignments, underscoring the approach's potential for structural elucidation in fields like organic chemistry, pharmaceuticals, and natural products.

Selective receptors of amino acids in aqueous media are highly sought after as they may enable the creation of novel diagnostic and sensing tools. Photoswitchable receptors are particularly attractive for such purposes as their response and selectivity towards bioanalytes can be modulated using light. Herein we report glucose-based photoswitchable receptors of amino-acid methyl esters and biogenic amines in water. The tetra-ortho-fluoroazobenzene unit in the receptors structure allows to control the distance between their binding sites using light. The Z-isomers of both receptors, having these sites in closer proximity, bind lysine, ornithine and arginine esters significantly stronger compared to E-isomers, where the binding sites are further apart.

RNA modifications are essential for the regulation of cellular processes and have a key role in diseases such as cancer and neurological disorders. A major challenge in the analysis of RNA modification is the differentiation between isomers, including methylated nucleosides as well as uridine and pseudouridine. A solution is their differential chemical reactivity which enables isomer discrimination by mass spectrometry (MS) or sequencing. In this study, we systematically determine the chemical reactivity of hydrazine with RNA and its native modifications in an aniline-free environment. We optimize the conditions to achieve nearly full conversion of all uridines while avoiding RNA cleavage. We apply the conditions to native tRNA^Phe which allows discrimination of pseudouridine and uridine by MALDI-MS. Furthermore, we determine the identity of the reaction product of hydrazine with various modified nucleosides using high resolution mass spectrometry and quantify the reaction yield in native tRNA from E. coli and human cells under various hydrazine conditions. Most modified nucleosides react quantitatively at lower hydrazine concentration while uridines do not decompose under these conditions. Thus, this study paves the way to exploit aniline-free hydrazine reactions in the detection of RNA modifications through MS and potentially even long-read RNA sequencing.

The development of experimental methodologies that enable investigations of biochemistry at high pressure promises to yield significant advances in our understanding of life on Earth and its origins. Here, we introduce a method for studying lipid membranes at thermodynamic conditions relevant for life at deep sea hydrothermal vents. Using in situ high pressure magic-angle spinning solid state nuclear magnetic resonance spectroscopy (NMR), we measure changes in the fluidity of model microbial membranes at pressures up to 28 MPa. We find that the fluid-phase lateral diffusion of phospholipids at high pressure is significantly affected by the stoichiometric ratio of lipids in the membrane. Our results were facilitated by an accessible pressurization strategy that we have developed to enable routine preparation of solid state NMR rotors to pressures of 30 MPa or greater.

The spin state of a metal center significantly influences the catalytic activity of its complex, a phenomenon so crucial that it has led to the dedicated field of spin catalysis. Here we investigate the effect of the spin state of an iron-based metal complex on the organic reactivity of its ligands. Specifically, we examined the post-synthetic modification of the spin crossover (SCO) complex [Fe(NH₂trz)₃](NO₃)₂ with p-anisaldehyde. A series of experiments were performed to study the transformation of the amino groups depending on the spin state of the metal. Owing to the wide thermal hysteresis loop of the SCO complex, both spin states were compared under identical conditions. The results revealed that the high-spin state led to the formation of 1.34 times more imine functional groups than the low-spin state, we propose that this arises from the different interactions between the solvent and the SCO at the different spin states.