Searching for a UV-filter in the eyes of high-flying birds.

The eye lens is a unique organ as no cells can be replaced throughout life. This makes it decisive that the lens is protected against damaging UV-radiation. An ultraviolet (UV)-absorbing compound of unknown identity is present in the aqueous humor of geese (wild and domestic) and other birds flying at high altitudes. A goose aqueous humor extract, that was believed to contain the UV protective compound which was designated as "compound X", was fractionated and examined using a variety of spectroscopic techniques including LC-MS and high field one- and two dimensional-NMR methods. A series of compounds were identified but none of them appeared to be the UV protective "compound X". It may be that the level of the UV protective compound in goose aqueous humor is much less than the compounds identified in our investigation, or it may have been degraded by the isolation and chromatographic purification protocols used in our investigations.

The Rich Solid-State Phase Behavior of l-Phenylalanine: Disappearing Polymorphs and High Temperature Forms.

After years of controversy over the solid state structure of the essential amino acid l-phenylalanine, four different polymorphic forms were published recently. The common form I has symmetry P21 with four molecules in the asymmetric unit (Z' = 4), similar to form III, but with a different arrangement of molecular bilayers. Form II, obtained from the hydrate at very low humidity, is unrelated to forms I and III, as is the high-density form IV. The present investigation demonstrates that this prototype aromatic amino acid has two additional high-temperature phases Ih and IIIh obtained from form I and form III above 458 and 440 K, respectively, when flipping between two alternative side-chain conformations becomes dynamic and causes pairs of molecules, initially crystallographically independent, to become equivalent above a sharp transition temperature. These abrupt and reversible phase changes occur with a reduction of Z' from 4 (low T) to 2 (high T) and modified crystal symmetry. We furthermore experienced an example of disappearing polymorph for form I which after growing form III in one of our laboratories could no longer be crystallized at room temperature. In contrast, form III crystals may be irreversibly converted to form I crystals as a result of sliding of molecular bilayers in the crystal at elevated temperature. No conversions between the high-temperature forms Ih and IIIh were found. The remarkable crystallographic results are here corroborated by Molecular Dynamics and metadynamics simulations of the form I - form III system.

Simulation of diffuse scattering in DL-norleucine.

The diffraction patterns of DL-norleucine (SR-2-aminohexanoic acid, DL-Nle) crystals may show obvious diffuse scattering, usually described as `streaking', between the Bragg peaks. This phenomenon is obviously related to the non-ideal behaviour of the crystal. The normal interpretation is disorder in the stacking of weakly interacting 2D layers, known also for a number of other racemates of amino acids with linear hydrophobic side chains, as well as 1:1 complexes between different L- and D-enantiomers (quasi-racemates). Presented here is the first attempt to extract the information hidden in the diffuse scattering for this group of compounds by applying Monte Carlo simulations to the site distributions of two polymorphs in a block of 48 × 48 × 48 unit cells (four sites in each unit cell, 442 368 in total). The results demonstrate that it is indeed possible to model the diffuse scattering and relate it to processes expected to take place during phase transitions, characterized by slipping of molecular bilayers (or parts of them) relative to their neighbours. The understanding of the (intermediate) mixed phases in terms of domain size and defect density is consequently brought to a new level.

Hydrophobic dipeptides: the final piece in the puzzle.

The crystal structure of L-valyl-L-leucine acetonitrile solvate presented here adds to 24 previously reported structures of dipeptides constructed from the five nonpolar amino acids L-alanine, L-valine, L-isoleucine, L-leucine and L-phenylalanine. It thus constitutes the final piece in the 5 × 5 puzzle of hydrophobic dipeptide structures. This opportunity is taken to review the crystal packing arrangements and hydrogen-bonding preferences of a rather unique group of substances, with updated information on the various hydrogen-bonding patterns and the associated peptide conformations.

Stereopermutation on the Putative Structure of the Marine Natural Product Mucosin.

A stereodivergent total synthesis has been executed based on the plausibly misassigned structure of the unusual marine hydrindane mucosin (1). The topological connectivity of the four contiguous all-carbon stereocenters has been examined by selective permutation on the highlighted core. Thus, capitalizing on an unprecedented stereofacial preference of the cis-fused bicycle[4.3.0]non-3-ene system when a Michael acceptor motif is incorporated, copper-mediated conjugate addition furnished a single diastereomer. Cued by the relative relationship reported for the appendices in the natural product, the resulting anti-adduct was elaborated into a probative target structure 1*.

Crystal structures of di-bromido-{N-[(pyridin-2-yl-κN)methyl-idene]picolinohydrazide-κ2N',O}cadmium methanol monosolvate and di-iodido{N-[(pyridin-2-yl-κN)methyl-idene]picolinohydrazide-κ2N',O}cadmium.

The title compounds, [CdBr2(C12H10N4O)]·CH3OH, (I), and [CdI2(C12H10N4O)], (II), are cadmium bromide and cadmium iodide complexes of the ligand (E)-N'-(pyridin-2-yl-methyl-ene)picolinohydrazide. Complex (I) crystallizes as the methanol monosolvate. In both compounds, the Cd2+ cation is ligated by one O atom and two N atoms of the tridentate ligand, and by two bromide anions forming a Br2N2O penta-coordination sphere for (I), and by two iodide anions forming an I2N2O penta-coordination sphere for (II), both with a distorted square-pyramidal geometry. In the crystal of complex (I), mol-ecules are linked by pairs of N-H⋯O and O-H⋯Br hydrogen bonds, involving the solvent mol-ecule, forming dimeric units, which are linked by C-H⋯Br hydrogen bonds forming layers parallel to (101). In the crystal of complex (II), mol-ecules are linked by N-H⋯I hydrogen bonds, forming chains propagating along [010]. In complex (II), measured at room temperature, the two iodide anions are each disordered over two sites; the refined occupancy ratio is 0.75 (2):0.25 (2).

Crystal structure of 6,7-dimeth-oxy-1-(4-nitro-phen-yl)quinolin-4(1H)-one: a mol-ecular scaffold for potential tubulin polymerization inhibitors.

The protein tubulin is central for maintaining normal cellular processes, and mol-ecules inter-fering with the tubulin dynamics have potential in the treatment of cancerous diseases. The title compound, C17H14N2O5, was prepared as a lead compound in a project dedicated to the development of therapeutic agents binding to the colchicine binding site on tubulin, thereby inter-fering with the cell division in cancer cells. It holds many of the main structural characteristics for colchicine binding and has the potential for further modification and functionalization. In the title mol-ecule, the benzene ring is inclined to the quinoline ring by 76.10 (8)°. In the crystal, mol-ecules are linked by two pairs of C-H⋯O hydrogen bonds, forming tubular-like arrangements, propagating along the direction of the diagonals of the ab plane, and enclosing R22(26) and R22(16) ring motifs.

A phase transition from monoclinic C2 with Z' = 1 to triclinic P1 with Z' = 4 for the quasiracemate L-2-aminobutyric acid-D-methionine (1/1).

Racemates of hydrophobic amino acids with linear side chains are known to undergo a unique series of solid-state phase transitions that involve sliding of molecular bilayers upon heating or cooling. Recently, this behaviour was shown to extend also to quasiracemates of two different amino acids with opposite handedness [Görbitz & Karen (2015). J. Phys. Chem. B, 119, 4975-4984]. Previous investigations are here extended to an L-2-aminobutyric acid-D-methionine (1/1) co-crystal, C4H9NO2·C5H11NO2S. The significant difference in size between the -CH2CH3 and -CH2CH2SCH3 side chains leads to extensive disorder at room temperature, which is essentially resolved after a phase transition at 229 K to an unprecedented triclinic form where all four D-methionine molecules in the asymmetric unit have different side-chain conformations and all three side-chain rotamers are used for the four partner L-2-aminobutyric acid molecules.

Crystal structure of l-leucyl-l-isoleucine 2,2,2-tri-fluoro-ethanol monosolvate.

Hydro-phobic dipeptides with either l-Leu or l-Phe constitute a rather heterogeneous group of crystal structures. Some form materials with large water-filled channels, but there is also a pronounced tendency to incorporate organic solvent mol-ecules, which then act as acceptors for one of the three H atoms of the charged N-terminal amino group. l-Leu-l-Ile has uniquely been obtained as two distinct hydrates, but has so far failed to co-crystallize with a simple alcohol. The present structure of C12H24N2O3·CF3CH2OH, which crystallizes with two dipeptide and two solvent mol-ecules in the asymmetric unit, demonstrates that when 2,2,2-tri-fluoro-ethanol is used as a solvent, its high capacity as a hydrogen-bond donor leads to formation of an alcohol solvate.

The development and use of a crystallographic database.

To scientists working with small-molecule or organometallic compounds, the Cambridge Structural Database constitutes an extremely important tool for reference to individual crystal structures and as a data source for statistical investigations. The article by Groom et al. [(2016), Acta Cryst. B72, 171-179] provides updated information on the use, development and future of this database.

An exceptional series of phase transitions in hydrophobic amino acids with linear side chains.

The solid-state phase transitions and intermediate structures of S-2-amino-butanoic acid (l-2-aminobutyric acid), S-2-aminopentanoic acid (l-norvaline), S-2-aminohexanoic acid (l-norleucine) and l-methionine between 100 and 470 K, identified by differential scanning calorimetry, have been characterized in a comprehensive single-crystal X-ray diffraction investigation. Unlike other enantiomeric amino acids investigated until now, this group featuring linear side chains displays up to five distinct phases. The multiple transitions between them involve a number of different processes: alteration of the hydrogen-bond pattern, to our knowledge the first example of this observed for an amino acid, sliding of molecular bilayers, seen previously only for racemates and quasiracemates, concerted side-chain rearrangements and abrupt as well as gradual modifications of the side-chain disorder. Ordering of l-norleucine upon cooling even proceeds via an incommensurately modulated structure. l-Methionine has previously been described as being fully ordered at room temperature. An accurate refinement now reveals extensive disorder for both molecules in the asymmetric unit, while two previously unknown phases occur above room temperature.

Microporous Molecular Materials from Dipeptides Containing Non-proteinogenic Residues.

Dipeptides with two hydrophobic side chains have proved to be an exceptional source of microporous organic materials, but since previous structures were limited to the incorporation of only proteinogenic residues, their full potential as adsorbents has remained unexplored. Single-crystal XRD data for ten new compounds with non-proteinogenic L-2-aminobutanoic acid and/or L-2-amino-pentanoic acid are presented. The gas-phase accessibility of their crystal pores, with cross-sections of 2.3 to 5.1 Å, was monitored by CO2 and CH4 adsorption isotherms. Included CO2 was also detected spectroscopically by 2D MAS NMR. An extensive conformational analysis reveals that the use of linear rather than branched side chains (such as L-valine and L-isoleucine) affords peptides with a greater degree of conformational freedom and yields more-flexible channel surfaces that may easily adapt to a series of potential guest molecules.

Crystal structure of seleno-l-cystine di-hydro-chloride.

Numerous crystal structures are available for the dimeric amino acid cystine. In proteins it is formed by oxidation of the -SH thiol groups of two closely spaced cysteine residues, resulting in the formation of a familiar di-sulfide bridge. The title compound [systematic name: (R,R)-1,1'-dicarb-oxy-2,2'-(diselanedi-yl)diethanaminium dichloride], C6H14N2O4Se2 (2+)·2Cl(-), is the first example of a small mol-ecule structure of the biologically important analogue with a -CH2-Se-Se-CH2- bridging unit. Bond lengths and angles of seleno-l-cystine di-hydro-chloride and its isotypic sulfur analogue l-cystine di-hydro-chloride are compared.

Redetermined crystal structure of ß-dl-me-thio-nine at 320†K.

The structure of ß-dl-me-thio-nine, C5H11NO2S, in the space group C2/c, is here confirmed to be fully ordered all the way up to the phase transition at approximately 326 K, where displacive sliding of mol-ecular bilayers gives the disordered P21/c α form [data at 340 K; Görbitz (2014). Acta Cryst. E70, 341-343]. The geometry of hydrogen bonds in LD-LD hydrogen-bonding patterns [Görbitz et al. (2009). Acta Cryst. B65, 393-400] at the hydro-philic core of each mol-ecular bilayer are virtually unperturbed by the phase shift, but the C-C-S-C torsion angle of the side chain changes from trans at 320 K to gauche+ for the major conformation at 340 K.

Crystal structure of (S)-2-[(3S,8S,9S,10R,13S,14S,17R)-3-hy-droxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-deca-hydro-1H-cyclo-penta[a]phenanthren-17-yl]-N-meth-oxy-N-methyl-pro-pan-amide (Fernholz Weinreb amide).

The literature compound 3ß-hy-droxy-bis-nor-5-cholenic aldehyde is an important inter-mediate for the synthesis of new modulators of the nuclear oxysterol receptor Liver X. As part of our ongoing search for new LXR antagonists, the title compound, C24H39NO3, has proven to be an important inter-mediate in our new synthetic pathway, giving the corresponding aldehyde in high yield and in only three steps from the commercially available 3ß-hy-droxy-bis-nor-5-cholenic acid. The title amide crystallized with two mol-ecules in the asymmetric unit, linked into helices by O-H⋯O hydrogen bonds involving the hy-droxy and carbonyl groups.

Twin displacive phase transitions in amino acid quasiracemates.

Three quasiracemates, L-norleucine:D-methionine, L-norvaline:D-norleucine, and L-norvaline:D-methionine, were crystallized to see how they differ from regular racemates in terms of crystal structure (studied by single-crystal X-ray diffraction) and of thermally induced phase transitions (studied by differential scanning calorimetry). Two types of transitions are detected between 100 and 450 K and structurally characterized: (1) displacive transitions of the molecular bilayers that form the crystal and (2) continuous or discontinuous disordering transitions in the amino acid side chains. Uniquely for the quasiracemates, the displacive transition proceeds in two close steps as only one surface of each molecular bilayer slides at first, upon forming an intermediate phase, while the other surface follows at a slightly higher temperature. Altogether, 18 new single-crystal structure-refinement data sets are reported for these three quasiracemates.

Redetermined crystal structure of α-dl-me-thio-nine at 340†K.

Two forms, α and ß, are known for the racemic amino acid dl-me-thio-nine, C5H11NO2S. The phase transition between them, taking place around 326 K, is associated with sliding at the central inter-faces of the hydro-phobic regions in the crystal, leaving the hydrogen-bonding pattern unperturbed. For the high-temperature α phase, only a structure of rather low quality has been available [R factor = 0.118, no H-atom coordinates; Taniguchi et al. (1980 ▶). Bull. Chem. Soc. Jpn, 53, 803-804]. We here present accurate structural data for this polymorph [R(F) = 0.049], which are compared with other related amino acid structures with similar properties. We report for the first time that the side chain of this phase has a minor disorder component [occupancy 0.0491 (18)] with a gauche+ rather than a gauche- conformation for the N-C-C-C group. In the crystal of the title compound, N-H⋯O hydrogen bonds link the mol-ecules into (100) sheets.

Redetermined structure of ß-dl-me-thio-nine at 105†K: an example of the importance of freely refining the positions of the amino-group H atoms.

Diffraction data were taken from the contribution named 'ß-dl-Me-thio-nine at 105 K' by Alagar et al. [Acta Cryst. (2005 ▶). E61, o1165-o1167]. Refinement of the coordinates of the three amino H atoms, previously constrained to an idealized geometry, shows that the amino group is in fact rotated 13.5° from the perfectly staggered orientation. This apparently modest change has a profound impact on the calculated hydrogen-bond geometries.

The polymorphs of L-phenylalanine.

The solid-state structure of the amino acid phenylalanine (Phe) offers a potential key to understanding the behavior of a large class of important aromatic compounds. Obtaining good single crystals is, however, notoriously difficult. The structure of the common polymorph of Phe, form I, was first reported by Weissbuch et al. (as D-Phe) in 1990, but the correctness of the published C2 unit cell with two disordered molecules in the asymmetric unit was later questioned and other space groups suggested. The identity of form I of L-Phe is here established to be P21 with Z'=4, based on data from a well-diffracting single crystal grown from an acetic acid solution of the amino acid. A second new polymorph, form IV, together with the two recently described forms II and III provide unprecedented information on the structural complexity of this essential amino acid. It is furthermore documented that the racemate, dl-Phe, does not grow proper single crystals.