3β‐(Stearyloxy)olean‐12‐ene from Austroplenckia populnea: Structure Elucidation by 2D‐NMR and Quantitative 13C‐NMR Spectroscopy

3β‐(Stearyloxy)olean‐12‐ene was isolated from a hexane extract of Austroplenckia populnea Reiss (Celastraceae) leaves. The structure was solved by means of quantitative ¹³C‐NMR, HMBC, HMQC, COSY, NOESY, and NOE difference spectra. The mass spectrum showed an [M+1]⁺ ion peak at m/z 693, and the molecular formula C₄₈H₈₄O₂ was confirmed by combustion analysis.     

The Structure Elucidation and Total Synthesis of β‐Lipomycin

Here we describe the synthesis of β‐lipomycin, a secondary metabolite isolated from the fermentation broth of Corallococcus coralloides. The synthesis relies on the structural assignment made by a statistical method, the so‐called profile hidden Markov model. Using this protocol, not only the configuration of the secondary alcohol, but also of the adjacent methyl branch could be deduced. The synthesis therefore not only provides access to this natural product but also confirms the validity of this approach for configurational assignment at methyl branches of modular polyketides.     

γ‐HIO3 – a Metastable,Centrosymmetric Polymorph of Iodic Acid

From solutions of chromium(III) perchlorate and periodic acid, single crystals of γ‐HIO₃ were obtained and characterized by single‐crystal X‐ray diffraction, Raman spectroscopy and thermal analysis. The compound crystallizes in the orthorhombic crystal system, space group Pbca (a = 563.92, b = 611.10, c = 1507.16 pm). The structure is built up by dimers (HIO₃)₂, which are formed by hydrogen bonds. The crystals are metastable and transform into the stable modification, α‐HIO₃, within a couple of weeks.     

The Crystal Structure of ζ2‐Al3Cu4‐δ

The crystal structure of the ζ₂‐phase Al₃Cu_4‐δ was determined by means of X‐ray powder diffraction: a = 409.72(1) pm, b = 703.13(2) pm, c = 997.93(3) pm, space group Imm2, Pearson symbol oI24‐3.5, R_I = 0.0696. ζ₂‐Al₃Cu_4‐δ forms a distinctive a × √3a × 2c superstructure of a metal deficient Ni₂In‐type‐related structure. The phase is meta‐stable at ambient temperature. Between 400 °C and 450 °C it decomposes into ζ₁‐Al₃Cu₄ and η₂‐AlCu. Entropic contributions to the stability of ζ₂‐Al₃Cu_4‐δ are reflected in three statistically or partially occupied sites.     

Ab‐initio Structure Determination of the New Ion Conductor K2Al2O3F2 from Powder Diffraction Data

The crystal structure of K₂Al₂O₃F_2, prepared at 800 °C by ceramic methods, was determined from conventional laboratory X‐ray powder diffraction data. The compound crystallizes in the monoclinic space group C2/m (No. 12) with a = 11.21675(8), b = 8.16351(6), c = 6.12301(5) Å β = 88.8108(6) ° and Z = 4. Unit cell and space group suggestions were found by using the TOPAS program. Starting positional parameters for potassium and aluminum atoms were obtained from 548 reflections by the methods implemented in the FOX program. Oxygen and fluorine atom positions were determined by structural considerations. The structure was refined using the fundamental parameter approach of TOPAS, which gave the final residuals (%) R_Bragg = 1.6 and R_wp = 4.6. The crystal structure consists of individual layers of oxygen connected AlO₃F tetrahedral groups with the fluorine atoms separating the layers. Empirical energy calculations agree with the crystal structure refinements and suggest no or little oxygen–fluorine exchange. Between and perpendicular to the sheets, the potassium ion can move without steric hindrance. Conductivity measurements from room temperature to 300 °C show decent potassium ion conductivity.     

De Novo 3D Structure Determination from Sub‐milligram Protein Samples by Solid‐State 100 kHz MAS NMR Spectroscopy

Solid‐state NMR spectroscopy is an emerging tool for structural studies of crystalline, membrane‐associated, sedimented, and fibrillar proteins. A major limitation for many studies is still the large amount of sample needed for the experiments, typically several isotopically labeled samples of 10–20 mg each. Here we show that a new NMR probe, pushing magic‐angle sample rotation to frequencies around 100 kHz, makes it possible to narrow the proton resonance lines sufficiently to provide the necessary sensitivity and spectral resolution for efficient and sensitive proton detection. Using restraints from such spectra, a well‐defined de novo structure of the model protein ubiquitin was obtained from two samples of roughly 500 μg protein each. This proof of principle opens new avenues for structural studies of proteins available in microgram, or tens of nanomoles, quantities that are, for example, typically achieved for eukaryotic membrane proteins by in‐cell or cell‐free expression.     

Preparation of Protected β2‐ and β3‐Homocysteine, β2‐ and β3‐Homohistidine,and β2‐Homoserine for Solid‐Phase Syntheses

The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β‐peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β³‐homoamino acid derivatives were obtained by Arndt–Eistert methodology from Boc‐His(Ts)‐OH and Fmoc‐Cys(PMB)‐OH (Schemes 2–4), with the side‐chain functional groups' reactivities requiring special precautions. The β²‐homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti‐enolates to formaldehyde (generated in situ from trioxane) and subsequent functional‐group manipulations. These include OH→O^tBu etherification (for β²hSer; Schemes 5 and 6), OH→STrt replacement (for β²hCys; Scheme 7), and CH₂OH→CH₂N₃→CH₂NH₂ transformations (for β²hHis; Schemes 9–11). Including protection/deprotection/re‐protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (t_R), melting points, optical rotations, HPLC on chiral columns, IR, ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X‐ray crystal‐structure analysis.     

Heterochromatin Protein HP1α Gelation Dynamics Revealed by Solid‐State NMR Spectroscopy

Heterochromatin protein 1α (HP1α) undergoes liquid–liquid phase separation (LLPS) and forms liquid droplets and gels in vitro, properties that also appear to be central to its biological function in heterochromatin compaction and regulation. Here we use solid‐state NMR spectroscopy to track the conformational dynamics of phosphorylated HP1α during its transformation from the liquid to the gel state. Using experiments designed to probe distinct dynamic modes, we identify regions with varying mobilities within HP1α molecules and show that specific serine residues uniquely contribute to gel formation. The addition of chromatin disturbs the gelation process while preserving the conformational dynamics within individual bulk HP1α molecules. Our study provides a glimpse into the dynamic architecture of dense HP1α phases and showcases the potential of solid‐state NMR to detect an elusive biophysical regime of phase separating biomolecules.     

Automated Solid‐Phase Synthesis and Structural Investigation of β‐Peptidosulfonamides and β‐Peptidosulfonamide/β‐Peptide Hybrids: β‐Peptidosulfonamide and β‐Peptide Foldamers are Two of a Different Kind

Fmoc‐protected β‐aminoethane sulfonylchlorides can be employed for efficient automated solid phase synthesis of β‐peptidosulfonamides and β‐peptidosulfonamide/β‐peptide hybrids containing one or more β‐peptidosulfonamide residues. Thus, Fmoc‐protected β‐aminoethane sulfonylchlorides 5a – c led to the hexa‐β‐peptidosulfonamide 9 and the nona‐β‐peptidosulfonamide 10 . In addition, the β‐peptidosulfonamide/β‐peptide hybrids 13 and 16 , consisting of six and nine β‐residues, respectively, and containing a single β‐peptidosulfonamide unit in the middle, as well as the peptidosulfonamide/β‐peptide hybrid 15 with nine β‐residues, including an N‐terminal β‐peptidosulfonamide residue, were synthesized by automated solid‐phase synthesis. Both CD and NMR spectroscopic measurements did not indicate any helical secondary structure for 9 and 10 . As was shown by CD‐measurements, the β‐peptidosulfonamide residue in the hybrids 13, 15 , and 16 acts as a ‘helix breaker', especially when located in the middle of the hybrid chain ( 13 and 16 ), but, although to a lesser extent, also at the N‐terminus.     

cyclo(β‐Asp‐β3‐hVal‐β3‐hLys) – Solid‐Phase Synthesis and Solution Structure of a Water Soluble β‐Tripeptide. Preliminary Communication

The H₂O‐soluble cyclic β³‐tripeptide cyclo(β‐Asp‐β³‐hVal‐β³‐hLys) ( 4 ) was obtained by on‐resin cyclization of the side‐chain‐anchored β‐peptide 3 (Scheme). In aqueous solution, 4 adopts a structure with uniformly oriented amide bonds and all side chains in lateral positions (Fig. 3).     

Enhancing NMR Sensitivity of Natural‐Abundance Low‐γ Nuclei by Ultrafast Magic‐Angle‐Spinning Solid‐State NMR Spectroscopy

Although magic‐angle‐spinning (MAS) solid‐state NMR spectroscopy has been able to provide piercing atomic‐level insights into the structure and dynamics of various solids, the poor sensitivity has limited its widespread application, especially when the sample amount is limited. Herein, we demonstrate the feasibility of acquiring high S/N ratio natural‐abundance ¹³C NMR spectrum of a small amount of sample (≈2.0 mg) by using multiple‐contact cross polarization (MCP) under ultrafast MAS. As shown by our data from pharmaceutical compounds, the signal enhancement achieved depends on the number of CP contacts employed within a single scan, which depends on the T_1ρ of protons. The use of MCP for fast 2D ¹H/¹³C heteronuclear correlation experiments is also demonstrated. The significant signal enhancement can be greatly beneficial for the atomic‐resolution characterization of many types of crystalline solids including polymorphic drugs and nanomaterials.     

β‐CuN3: The Overlooked Ground‐State Polymorph of Copper Azide with Heterographene‐Like Layers

An unexpected polymorph of the highly energetic phase CuN₃ has been synthesized and crystallizes in the orthorhombic space group Cmcm with a=3.3635(7), b=10.669(2), c=5.5547(11) Å and V=199.34(7) ų. The layered structure resembles graphite with an interlayer distance of 2.777(1) Å (=1/2 c). Within a single layer, considering N₃^? as one structural unit, there are 10‐membered almost hexagonal rings with a heterographene‐like motif. Copper and nitrogen atoms are covalently bonded with Cu? N bonds lengths of 1.91 and 2.00 Å, and the N₃^? group is linear but with N? N 1.14 and 1.20 Å. Electronic‐structure calculations and experimental thermochemistry show that the new polymorph termed β‐CuN₃ is more stable than the established α‐CuN₃ phase. Also, β‐CuN₃ is dynamically, and thus thermochemically, metastable according to the calculated phonon density of states. In addition, β‐CuN₃ exhibits negative thermal expansion within the graphene‐like layer.     

X‐ray Diffraction and Solid‐State NMR Studies of a Germanium Binuclear Complex

A compound formulated as (C₄H₁₂N₂)[Ge₂(pmida)₂(OH)₂] ? 4 H₂O (where pmida^4?=N‐(phosphonomethyl)iminodiacetate and C₄H₁₂N₂²⁺=piperazinedium cation), containing the anionic [Ge₂(pmida)₂(OH)₂]^2? complex, has been synthesised by the hydrothermal approach and its structure determined by single‐crystal X‐ray diffraction analysis. Several high‐resolution solid‐state magic‐angle spinning (MAS) NMR techniques, in particular two‐dimensional ¹H–X(¹³C,³¹P) heteronuclear correlation (HETCOR) and ¹H–¹H homonuclear correlation (HOMCOR) experiments incorporating a frequency‐switched Lee–Goldburg (FS‐LG) decoupling scheme, have been employed for the first time in such a material. Using these tools in tandem affords an excellent general approach to study the structure of other inorganic–organic hybrids. We assigned the NMR resonances with the help of C ??? H and P ??? H internuclear distances obtained through systematic statistical analyses of the crystallographic data. The compound was further characterised by powder X‐ray diffraction techniques, IR and Raman spectroscopy, and by elemental and thermal analyses (thermogravimetric analysis and differential scanning calorimetry).