Unravelling the Time Scale of Conformational Plasticity and Allostery in Glycan Recognition by Human Galectin-1

The interaction of human galectin-1 with a variety of oligosaccharides, from di-(N-acetyllactosamine) to tetra-saccharides (blood B type-II antigen) has been scrutinized by using a combined approach of different NMR experiments, molecular dynamics (MD) simulations, and isothermal titration calorimetry. Ligand- and receptor-based NMR experiments assisted by computational methods allowed proposing three-dimensional structures for the different complexes, which explained the lack of enthalpy gain when increasing the chemical complexity of the glycan. Interestingly, and independently of the glycan ligand, the entropy term does not oppose the binding event, a rather unusual feature for protein-sugar interactions. CLEANEX-PM and relaxation dispersion experiments revealed that sugar binding affected residues far from the binding site and described significant changes in the dynamics of the protein. In particular, motions in the microsecond-millisecond timescale in residues at the protein dimer interface were identified in the presence of high affinity ligands. The dynamic process was further explored by extensive MD simulations, which provided additional support for the existence of allostery in glycan recognition by human galectin-1.     

Electrophilicity Scale of Activated Amides: 17O NMR and 15N NMR Chemical Shifts of Acyclic Twisted Amides in N−C(O) Cross-Coupling

The structure and properties of amides are of tremendous interest in organic synthesis and biochemistry. Traditional amides are planar and the carbonyl group non-electrophilic due to n_N→π*_C=O conjugation. In this study, we report electrophilicity scale by exploiting ¹⁷O NMR and ¹⁵N NMR chemical shifts of acyclic twisted and destabilized acyclic amides that have recently received major attention as precursors in N-C(O) cross-coupling by selective oxidative addition as well as precursors in electrophilic activation of N-C(O) bonds. Most crucially, we demonstrate that acyclic twisted amides feature electrophilicity of the carbonyl group that ranges between that of acid anhydrides and acid chlorides. Furthermore, a wide range of electrophilic amides is possible with gradually varying carbonyl electrophilicity by steric and electronic tuning of amide bond properties. Overall, the study quantifies for the first time that steric and electronic destabilization of the amide bond in common acyclic amides renders the amide bond as electrophilic as acid anhydrides and chlorides. These findings should have major implications on the fundamental properties of amide bonds.     

Reducing the computational cost of NMR crystallography of organic powders at natural isotopic abundance with the help of 13C-13C dipolar couplings

Structure determination of functional organic compounds remains a formidable challenge when the sample exists as a powder. Nuclear magnetic resonance crystallography approaches based on the comparison of experimental and Density Functional Theory (DFT)-computed ¹H chemical shifts have already demonstrated great potential for structure determination of organic powders, but limitations still persist. In this study, we discuss the possibility of using ¹³C-¹³C dipolar couplings quantified on powdered theophylline at natural isotopic abundance with the help of dynamic nuclear polarization, to realize a DFT-free, rapid screening of a pool of structures predicted by ab initio random structure search. We show that although ¹³C-¹³C dipolar couplings can identify structures possessing long range structural motifs and unit cell parameters close to those of the true structure, it must be complemented with other data to recover information about the presence and the chemical nature of the supramolecular interactions.     

Investigating Chain Dynamics in Highly Crosslinked Polymers using Solid‐State 1H NMR Spectroscopy

Solid state ¹H NMR line‐shape analysis and (double quantum) DQ ¹H NMR experiments have been used to investigate the segmental and polymer chain dynamics as a function of temperature for a series of thermosetting epoxy resins produced using different diamine curing agents. In these thermosets, chemical crosslinks introduce topological constraints leading to residual stresses during curing. Materials containing a unique ferrocene‐based diamine (FcDA) curing agent were evaluated to address the role of the ferrocene fluxional process on the atomic‐level polymer dynamics. At temperatures above the glass transition temperature (T_g), the DQ ¹H NMR experiments provided a measure of the relative effective crosslink and entanglement densities for these materials and revealed significant polymer chain dynamic heterogeneity in the FcDA‐cured thermosets. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 1143–1156     

Short Syntheses of some ‘Decalin‐1,8‐diones’ and their Derivatives: Breaking the Pretended Symmetry

A cheap synthesis of the so‐called ‘decalin‐1,8‐diones’ started with the conjugate (1,4‐) addition of cyclohex‐2‐en‐1‐one derivatives to the γ‐position of the dilithium derivative (buta‐1,3‐diene‐1,1‐bis(olate)) of crotonic acid. Hydrogenation of these ‘1,4‐γ’ adducts and final cyclization afforded the enol tautomers of decalin‐1,8‐diones. Nucleophilic substitutions at these 3‐oxoenols by NH₃ or primary amines created only monoamino products (namely, 3‐oxoenamines) whose reactions with OPCl₃ yielded dihydro(1,3,2)oxazaphosphinin‐2‐one derivatives. The two regioisomers of a trimethyl‐3‐oxoenamine served as models for the constitutional assignments of the two rapidly interconverting (hence, individually NMR‐invisible), tautomeric trimethyl‐3‐oxoenols. Such methyl substitutions served to break the ‘pretended’ symmetry of ‘decalin‐1,8‐dione’. Hydrazine and 3‐oxoenols furnished oxygen‐free indazole derivatives whose N?H bonds exchanged with t_1/2=ca. 0.00035 s at ca. ?58(9) °C.     

Solid-State NMR Spectroscopy: A Powerful Technique to Directly Study Small Gas Molecules Adsorbed in Metal–Organic Frameworks

Metal–organic frameworks (MOFs) have shown great potential in gas separation and storage, and the design of MOFs for these purposes is an on-going field of research. Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a valuable technique for characterizing these functional materials. It can provide a wide range of structural and motional insights that are complementary to and/or difficult to access with alternative methods. In this Concept article, the recent advances made in SSNMR investigations of small gas molecules (i.e., carbon dioxide, carbon monoxide, hydrogen gas and light hydrocarbons) adsorbed in MOFs are discussed. These studies demonstrate the breadth of information that can be obtained by SSNMR spectroscopy, such as the number and location of guest adsorption sites, host–guest binding strengths and guest mobility. The knowledge acquired from these experiments yields a powerful tool for progress in MOF development.     

NMR Reveals That a Highly Reactive Nonheme FeIV=O Complex Retains Its Six-Coordinate Geometry and S=1 State in Solution

The [Fe^IV(O)(Me₃NTB)]²⁺ (Me₃NTB=tris[(1-methyl-benzimidazol-2-yl)methyl]amine) complex 1 has been shown by Mössbauer spectroscopy to have an S=1 ground state at 4 K, but is proposed to become an S=2 trigonal-bipyramidal species at higher temperatures based on a DFT model to rationalize its very high C−H bond-cleavage reactivity. In this work, ¹H NMR spectroscopy was used to determine that 1 does not have C₃-symmetry in solution and is not an S=2 species. Our results show that 1 is unique among nonheme Fe^IV=O complexes in retaining its S=1 spin state and high reactivity at 193 K, providing evidence that S=1 Fe^IV=O complexes can be as reactive as their S=2 counterparts. This result emphasizes the need to identify factors besides the ground spin state of the Fe^IV=O center to rationalize nonheme oxoiron(IV) reactivity.     

Quaternary ammonium compounds in roots and leaves of Capparis spinosa L. from Saudi Arabia and Italy: investigation by HPLC-MS and 1H NMR

Capparis spinosa L. is a perennial plant typical of the Mediterranean flora and a multipurpose plant used for curing various human ailments. Quaternary ammonium compounds (QACs), as constituents of Capparaceae, play important roles in protecting against abiotic stress. Aim of this work was to determine QACs in root and leaves of caper from two proveniences. The presence of stachydrine, choline, glycine betaine and homo-stachydrine has been confirmed by high resolution MS, while ¹H NMR was applied to quantify the main QACs in the aqueous extracts. Stachydrine was quantified at 20.2 mg/g and 32.3 mg/g on dry leaves from South of Italy and Saudi Arabia, respectively, while a minor content was in dry roots (from 10.4 to 12.5 mg/g). Choline was considerably lower both in leaves and roots (from 0.3 to 1.2 mg/g). To our knowledge, this is the first report on the determination of QACs both in root and leaves of C. spinosa.     

Re-Evaluation of a Fulvene-Based Self-Replicating Diels–Alder Reaction System

We re-evaluate our claim of a high diastereoselectivity in the self-relicating Diels–Alder reaction between maleimide 1 and fulvene 3 . It was shown that the system has a diastereoselectivity of 1.8:1 for NN-4 : NX-4 , which is contrary to the 16:1 ratio claimed by Dieckmann et al. The analysis of ¹H NMR monitoring of the reaction revealed that both replicators show sigmoidal growth which is typical for auto-catalytic systems.     

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst

NMR offers many possibilities in chemical analysis, structural investigations, and medical diagnostics. Although it is broadly used, one of NMR spectroscopies main drawbacks is low sensitivity. Hyperpolarization techniques enhance NMR signals by more than four orders of magnitude allowing the design of new contrast agents. Parahydrogen induced polarization that utilizes the para-hydrogen's singlet state to create enhanced signals is of particular interest since it allows to produce molecular imaging agents within seconds. Herein, we present a strategy for signal enhancement of the carbonyl ¹³C in amino acids by using parahydrogen, as demonstrated for glycine and alanine. Importantly, the hyperpolarization step is carried out in water and chemically unmodified canonical amino acids are obtained. Our approach thus offers a high degree of biocompatibility, which is crucial for further application. The rapid sample hyperpolarization (within seconds) may enable the continuous production of biologically useful probes, such as metabolic contrast agents or probes for structural biology.