Bergofungin D, a peptaibol template for the introduction of chemical modifications, synthesis of analogs and comparative studies of their structures.

Bergofungin D is a helical peptide of the peptaibol family consisting of 14 amino acids, six of which are the helix inducer aminoisobutyric acid (Aib). In the second third of the sequence, a hydroxyproline causes a bending of the helix and a disruption of the hydrogen bond network, and Aib7 is the only amino acid in this region involved in the hydrogen bond network. Therefore, modification of this residue can serve as a probe to monitor the effect of introducing amino acid substitutions on this more fragile helical turn. To validate this approach, we simplified the original bergofungin D by reducing the number of non-classical amino acids, replacing the (R)-isovaleric acid by its enantiomer or an Aib and the hydroxyproline with a proline, respectively, without affecting its secondary structure. Within the modified structure, we replaced Aib7-Aib8 by its 1,2,3-triazolodipeptide equivalent or Aib7 by a serine or a dehydrobutyrine. We have reported and analyzed five crystal structures, three of which are new, demonstrating the usefulness of the modified bergofungin D as a probe for monitoring the introduction of amino acid substitutions within a helical structure.

Synthesis, structure and Hirshfeld surface analysis of 2-oxo-2H-chromen-6-yl 4-tert-butyl-benzoate: work carried out as part of the AFRAMED project.

In the title compound, C20H18O4, the dihedral angle between the 2H-chromen-2-one ring system and the phenyl ring is 89.12 (5)°. In the crystal, the mol-ecules are connected through C-H⋯O hydrogen bonds to generate [010] double chains that are reinforced by weak aromatic π-π stacking inter-actions. The unit-cell packing can be described as a tilted herringbone motif. The H⋯H, H⋯O/O⋯H, H⋯C/C⋯H and C⋯C contacts contribute 46.7, 24.2, 16.7 and 7.6%, respectively, to its Hirshfeld surface.

Pas de Deux of an NO Couple: Synchronous Photoswitching from a Double-Linear to a Double-Bent Ru(NO)2 Core under Nitrosyl Charge Conservation.

The {Ru(NO)2 }10 dinitrosylruthenium complex [Ru(NO)2 (PPh3 )2 ] (1) shows photo-induced linkage isomerism (PLI) of a special kind: the two NO ligands switch, on photo-excitation, synchronously from the ground state (GS) with two almost linear RuNO functions to a metastable state (MS) which persists up to 230 K and can be populated to ≈50 %. The MS was experimentally characterised by photo-crystallography, IR spectroscopy and DS-calorimetry as a double-bent variant of the double-linear GS. The experimental results are confirmed by computation which unravels the GS/MS transition as a disrotatory synchronous 50° turn of the two nitrosyl ligands. Although 1 shows the usual redshift of the N-O stretch on bending the MNO unit, there is no increased charge transfer from Ru to NO along the GS-to-MS path. In terms of the effective-oxidation-state (EOS) method, both isomers of 1 and the transition state are Ru-II (NO+ )2 species.

N-Iodosaccharin-pyridine co-crystal system under pressure: experimental evidence of reversible twinning.

This work presents a single-crystal X-ray diffraction study of an organic co-crystal composed of N-iodosaccharin and pyridine (NISac·py) under hydrostatic pressure ranging from 0.00 (5) GPa to 4.5 (2) GPa. NISac·py crystallizes in the monoclinic system (space group B21/e). The unconventional setting of the space group is adopted (the conventional setting is P21/c, No. 14) to emphasise the strongly pseudo-orthorhombic symmetry of the lattice, with a ß angle very close to 90°. The crystal structure contains one molecule each of N-iodosaccharin (NISac) and pyridine (py) in the asymmetric unit (Z' = 1), linked via an Nsac...I...N'py halogen-bonding motif. A gradual modification of this motif is observed under pressure as a result of changes in the crystalline environment. Mechanical twinning is observed under compression and the sample splits into two domains, spanning an unequal volume that is mapped by a twofold rotation about the [100] direction of the B21/e unit cell. The twinning is particularly significant at high pressure, being reversible when the pressure is released. The structure of the twinned sample reveals the continuity of a substantial substructure across the composition plane. The presence of this common substructure in the two orientations of the twinned individuals can be interpreted as a structural reason for the formation of the twin and is the first observed example in a molecular crystal. These results indicate that the anisotropy of intermolecular interactions in the crystal structure results in an anisotropic strain generated upon the action of hydrostatic compression. Periodic density functional theory calculations were carried out by considering an isotropic external pressure, the results showing good agreement with the experimental findings. The bulk modulus of the crystal was obtained from the equations of state, being 7 (1) GPa for experimental data and 6.8 (5) GPa for theoretical data.

The Coordination Behavior of Two New Complexes, [(C7H10NO2)CdCl3]n(I) and [(C7H9NO2)CuCl2] (II), Based on 2,6-Dimethanolpyridine; Elaboration of the Structure and Hirshfeld Surface, Optical, Spectroscopic and Thermal Analysis.

Two novel complexes, [(C7H10NO2)CdCl3]n(I) and [(C7H9NO2)CuCl2],havebeen synthesized and characterized. Single crystal X-ray diffraction revealed that in compound (I), 2,6-dimethanol pyridinium acts as a monodentate ligand through the O atom of the hydroxyl group. Contrarily, the 2,6-dimethanol pyridine ligand interacts tridentately with the Cu(II) ion via the nitrogen atoms and the two oxygen (O, O') atoms of the two hydroxyl groups. The structure's intermolecular interactions were studied using contact enrichment ratios and Hirshfeld surfaces. Following metal coordination, numerous hydrogen connections between entities and parallel displacement stacking interactions between pyridine rings dictate the crystal packing of both compounds. The aromatic cycles generate layers in the crystal for both substances. Powder XRD measurements confirmed the crystalline sample phase purity. SEM confirmed the surface homogeneity, whereas EDX semi-quantitative analysis corroborated the composition. IR spectroscopy identified vibrational absorption bands, while optical UV-visible absorption spectroscopy investigated optical properties. The thermal stability of the two materials was tested using TG-DTA.

Humidity-Sensing Properties of an 1D Antiferromagnetic Oxalate-Bridged Coordination Polymer of Iron(III) and Its Temperature-Induced Structural Flexibility.

A novel one-dimensional (1D) oxalate-bridged coordination polymer of iron(III), {[NH(CH3)(C2H5)2][FeCl2(C2O4)]}n (1), exhibits remarkable humidity-sensing properties and very high proton conductivity at room temperature (2.70 × 10-4 (Ω·cm)-1 at 298 K under 93% relative humidity), in addition to the independent antiferromagnetic spin chains of iron(III) ions bridged by oxalate groups (J = -7.58(9) cm-1). Moreover, the time-dependent measurements show that 1 could maintain a stable proton conductivity for at least 12 h. Charge transport and magnetic properties were investigated by impedance spectroscopy and magnetization measurements, respectively. Compound 1 consists of infinite anionic zig-zag chains [FeCl2(C2O4)]nn- and interposed diethylmethylammonium cations (C2H5)2(CH3)NH+, which act as hydrogen bond donors toward carbonyl oxygen atoms. Extraordinarily, the studied coordination polymer exhibits two reversible phase transitions: from the high-temperature phase HT to the mid-temperature phase MT at T ~213 K and from the mid-temperature phase MT to the low-temperature phase LT at T ~120 K, as revealed by in situ powder and single-crystal X-ray diffraction. All three polymorphs show large linear thermal expansion coefficients.

Towards Iron(II) Complexes with Octahedral Geometry: Synthesis, Structure and Photophysical Properties.

The control of ligand-field splitting in iron (II) complexes is critical to slow down the metal-to-ligand charge transfer (MLCT)-excited states deactivation pathways. The gap between the metal-centered states is maximal when the coordination sphere of the complex approaches an ideal octahedral geometry. Two new iron(II) complexes (C1 and C2), prepared from pyridylNHC and pyridylquinoline type ligands, respectively, have a near-perfect octahedral coordination of the metal. The photophysics of the complexes have been further investigated by means of ultrafast spectroscopy and TD-DFT modeling. For C1, it is shown that-despite the geometrical improvement-the excited state deactivation is faster than for the parent pseudo-octahedral C0 complex. This unexpected result is due to the increased ligand flexibility in C1 that lowers the energetic barrier for the relaxation of 3MLCT into the 3MC state. For C2, the effect of the increased ligand field is not strong enough to close the prominent deactivation channel into the metal-centered quintet state, as for other Fe-polypyridine complexes.

Photocrystallographic and spectroscopic studies of a model (N,N,O)-donor square-planar nickel(II) nitro complex: in search of high-conversion and stable photoswitchable materials.

A new, cheap, easy-to-synthesize and air-stable photoswitchable nickel(II) complex, QTNiNO2, is reported. The metal centre in QTNiNO2 is coordinated by a nitro group and a [2-methyl-8-amino-quinoline]-1-tetralone ligand. The compound crystallizes in the tetragonal space group I41/a with one complex molecule comprising the asymmetric unit, and the crystals are stable under ambient conditions. Irradiation of the solid-state form of QTNiNO2 with 530-660 nm LED light at 160 K converts the ambidentate nitro moiety fully to the nitrito linkage isomer which is stable up to around 230 K, as indicated by IR spectroscopy measurements. The structures of all species present in the examined crystals and their thermal stability were confirmed via X-ray multi-temperature and photocrystallographic experiments. The impact of temperature on the (photo)isomerization reaction taking place in a single crystal was additionally investigated. The experimental results are supported by computational analyses of crystal packing and intermolecular interactions that influence the isomerization process studied.

Crystal structure of di-ammonium bis-[tris-(oxamide dioxime-κ2 N,N')nickel(II)] bis-[tris-(oxalato-κ2 O,O')chromate(III)] 6.76-hydrate.

The asymmetric unit of the title compound, (NH4)2[Ni(C2H6N4O2)3]2[Cr(C2O4)3]2·6.76H2O, comprises two NH4 + cations, two [Ni(C2H6N4O2)3]2+ cations and two [Cr(C2O4)3]3- anions, as well as eight water mol-ecules of crystallization of which only one is fully occupied. In the cationic and anionic complexes, the central atoms (NiII and CrIII) are each surrounded by three bidentate ligands (N-chelating oxamide dioxime and O-chelating oxalate, respectively), resulting in distorted octa-hedral coordination spheres. In the crystal, O-H⋯O hydrogen bonds between the oxamide dioxime ligands as donor groups and the oxalate ligands as acceptor groups alternately connect the cationic and anionic complexes into infinite pillars extending parallel to [100]. Moreover, N-H⋯O hydrogen bonds between the same ligands connect neighboring pillars, thus delineating channels that accommodate the charge-balancing NH4 + cations as well as the water mol-ecules of crystallization. Although the H atoms could not be localized for these two species, the corresponding N⋯O and O⋯O distances indicate hydrogen bonds of medium strength.

Hexa-aqua-nickel(II) bis-[tri-aqua-µ3-oxalato-di-µ-oxalato-bariumchromate(III)] tetra-hydrate.

The title compound, [Ni(H2O)6][BaCr(C2O4)3(H2O)3]2·4H2O, was obtained in the form of single crystals from the slow evaporation of an aqueous mixture of {Ba6(H2O)17[Cr(C2O4)3]4}·7H2O and NiSO4·6H2O in the molar ratio 1:4. Its structure is made up of corrugated anionic (101) layers of formula [BaCr(C2O4)3(H2O)3] n n - that leave voids accommodating the charge-compensating cations, [Ni(H2O)6]2+ (point group symmetry ), as well as the water mol-ecules of crystallization. The anionic layers are built from the connection of barium and chromium atoms through bridging oxalate ligands. The CrIII atom is hexa-coordinated by O atoms of three oxalate ligands while the BaII atom is tenfold coordinated by three O atoms of water mol-ecules and seven O atoms of four oxalate ligands. Each NiII atom sits on an inversion center and is coordinated by six water mol-ecules. One of the uncoordinated water mol-ecules is disordered over two sites, with a refined occupancy ratio of 0.51 (5):0.49 (5). In the crystal, extensive O-H⋯O hydrogen-bonding inter-actions link the anionic layers, the charge-balancing cations as well as the water mol-ecules of crystallization into a three-dimensional supra-molecular network.

A bicyclic unit reversal to stabilize the 12/14-helix in mixed homochiral oligoureas.

The insertion of cyclic building blocks in oligoureas to stabilize or modulate the properties of the 12/14-helix was often fruitless. We herein propose a fully compatible highly constrained building block that could be incorporated into oligoureas to develop highly stable and functional oligoureas helices.

Synthesis, structural elucidation, characterization and theoretical DFT study of 1-(o-tolyl)biguanidium chloride.

The structure of the new salt 1-(o-tolyl)biguanidium chloride, C9H14N5+·Cl-, has been determined by single-crystal X-ray diffraction. The salt crystallizes in the monoclinic space group C2/c. In this structure, the chloride and biguanidium hydrophilic ions are mostly connected to each other via N-H...N and N-H...Cl hydrogen bonds to form layers parallel to the ab plane around y = 1/3 and y = 2/3. The 2-methylbenzyl groups form layers between these layers around y = 0 and y = 1/2, with the methyl group forming C-H...π interactions with the aromatic ring. Intermolecular interactions on the Hirshfeld surface were investigated in terms of contact enrichment and electrostatic energy, and confirm the role of strong hydrogen bonds along with hydrophobic interactions. A correlation between electrostatic energy and contact enrichment is found only for the strongly attractive (N-H...Cl-) and repulsive contacts. Electrostatic energies between ions reveal that the interacting biguanidium cation pairs are repulsive and that the crystal is maintained by attractive cation...Cl- dimers. The vibrational absorption bands were identified by IR spectroscopy.

Crystal structure of a new phen-yl(morpholino)methane-thione derivative: 4-[(morpholin-4-yl)carbothioyl]benzoic acid.

4-[(Morpholin-4-yl)carbothioyl]benzoic acid, C12H13NO3S, a novel phen-yl(morpholino)methane-thione derivative, crystallizes in the monoclinic space group P21/n. The morpholine ring adopts a chair conformation and the carb-oxy-lic acid group is bent out slightly from the benzene ring mean plane. The mol-ecular geometry of the carb-oxy-lic group is characterized by similar C-O bond lengths [1.266 (2) and 1.268 (2) Å] as the carboxyl-ate H atom is disordered over two positions. This mol-ecular arrangement leads to the formation of dimers through strong and centrosymmetric low barrier O-H⋯O hydrogen bonds between the carb-oxy-lic groups. In addition to these inter-molecular inter-actions, the crystal packing consists of two different mol-ecular sheets with an angle between their mean planes of 64.4 (2)°. The cohesion between the different layers is ensured by C-H⋯S and C-H⋯O inter-actions.

Room-Temperature Photogeneration of Nitrosyl Linkage Isomers in Ruthenium Nitrosyl Complexes.

The conditions for the photogeneration of NO linkage isomers at room temperature are studied. By pulsed laser irradiation in the blue spectral range, the long-lived Ru-ON isomer can be generated at room temperature, which is crucial for potential applications, such as holography and data storage. By using static and time-resolved spectroscopy (UV/Vis and IR), we give evidence that the liftime of the Ru-(η2 -(NO)) isomer is a decisive parameter for the formation of the Ru-ON isomer at high temperature owing to a two-step isomerization mechanism Ru-NO→Ru-(η2 -(NO))→Ru-ON. Furthermore, we report the low-temperature structures for each isomer, which were revealed by photocrystallography.

Combining photoinduced linkage isomerism and nonlinear optical properties in ruthenium nitrosyl complexes.

The complex trans-[RuNO(NH3)4F]SiF6 was synthesized in quantitative yield and the structure was characterized by X-ray diffraction and spectroscopic methods. The complex crystallizes in the non-centrosymmetric space group Pn. Hirshfeld surface analysis revealed that the dominant intermolecular interactions are of types H...F and F...O, which are likely to be responsible for the packing of the molecules in a non-centrosymmetric structure. Irradiation with blue light leads to the formation of Ru-ON (metastable state MS1) and Ru-η2-(NO) (metastable state MS2) bond isomers, as shown by IR and UV-Vis spectroscopy. The structural features of the MS1 isomer were elucidated by photocrystallography. The complex exhibits exceptionally good thermal stability of the metastable state MS1, such that it can be populated by light at 290-300 K, which is important for potential applications. The second harmonic (SH) emission can be generated by femtosecond-pulsed irradiation of the complex. The generated SH is rather efficient and stable under long-term exposure. Finally, since both metastable states and harmonic generation can be generated at room temperature, an attempt to drive the SH response by photoisomerization of the nitrosyl ligand was made and is discussed.

12/10-Helix in Mixed ß-Peptides Alternating Bicyclic and Acyclic ß-Amino Acids: Probing the Relationship between Bicyclic Side Chain and Helix Stability.

12/10-Helices constitute suitable templates that can be used to design original structures. Nevertheless, they often suffer from a weak stability in polar solvents because they exhibit a mixed hydrogen-bond network resulting in a small macrodipole. In this work, stable and functionalizable 12/10-helices were developed by alternating a highly constrained ß2, 3, 3 -trisubstituted bicyclic amino acid (S)-1-aminobicyclo[2.2.2]octane-2-carboxylic acid ((S)-ABOC) and an acyclic substituted ß-homologated proteinogenic amino acid (l-ß3 -hAA). Based on NMR spectroscopic analysis, it was shown that such mixed ß-peptides display well-defined right-handed 12/10-helices in polar, apolar, and chaotropic solvents; that are, CD3 OH, CDCl3 , and [D6 ]DMSO, respectively. The stability of the hydrogen bonds forming the C10 and C12 pseudocycles as well as the benefit provided by the use of the constrained bicyclic ABOC versus typical acyclic ß-amino acids sequences when designing 12/10-helix were investigated using NH/ND NMR exchange experiments and DFT calculations in various solvents. These studies showed that the ß3 -hAA/(S)-ABOC helix displayed a more stable hydrogen-bond network through specific stabilization of the C10 pseudocycles involving the bridgehead NH of the ABOC bicyclic scaffold.

Synthesis of [1,2,4]Triazolo[4,3- a]piperazin-6-ones: An Approach to the Triazole-Fused Ketopiperazine Scaffold.

A stereoconservative synthesis to access the triazole-fused ketopiperazine (TKP) scaffold is presented. This underexplored platform offers a wide range of structural modulations with several points of diversity and chiral centers. A series of [1,2,4]triazolo[4,3- a]piperazin-6-ones was synthesized from optically pure dipeptides. The methodology was then successfully applied to access the pyrrolo[1,2- a]triazolo[3,4- c]piperazin-6-one tricycle. Importantly, the crystal structures of representative TKPs confirmed that the configuration of the chiral centers was controlled during the synthetic route and facilitated description of the orientation of the substituents depending on their nature and position on the TKP scaffold.

How are 1,2,3-triazoles accommodated in helical secondary structures?

1,4-Disubstituted-1,2,3-triazole (Tz) is widely used in peptides as a trans-amide bond mimic, despite having hazardous effects on the native peptide activity. The impact of amide bond substitution by Tz on peptide secondary structures is scarcely documented. We performed a Tz scan, by systematically replacing peptide bonds following the Aib residues with Tz on two model peptaibols: alamethicin F50/5 and bergofungin D, which adopt stable α- and 310 helices, respectively. We observed that the Tz insertion, whatever its position in the peptide sequences, abolished their antimicrobial activity. The structural consequences of this insertion were further investigated using CD, NMR and X-ray diffraction. Importantly, five crystal structures that were incorporated with Tz were solved, showing various degrees of alteration of the helical structures, from minor structural perturbation of the helix to partial disorder. Together, these results showed that Tz insertions impair helical secondary structures.

C9/12 Ribbon-Like Structures in Hybrid Peptides Alternating α- and Thiazole-Based γ-Amino Acids.

According to their restricted conformational freedom, heterocyclic γ-amino acids are usually considered to be related to Z-vinylogous γ-amino acids. In this context, oligomers alternating α-amino acids and thiazole-based γ-amino acids (ATCs) were expected to fold into a canonical 12-helical shape as described for α/γ-hybrid peptides composed of cis-α/ß-unsaturated γ-amino acids. However, through a combination of X-ray crystallography, NMR spectroscopy, FTIR experiments, and DFT calculations, it was determined that the folding behavior of ATC-containing hybrid peptides is much more complex. The homochiral α/(S)-ATC sequences were unable to adopt a stable conformation, whereas the heterochiral α/(R)-ATC peptides displayed novel ribbon structures stabilized by unusual C9/12 -bifurcated hydrogen bonds. These ribbon structures could be considered as a succession of pre-organized γ/α dipeptides and may provide the basis for designing original α-helix mimics.

Enhancing the Antimicrobial Activity of Alamethicin F50/5 by Incorporating N-terminal Hydrophobic Triazole Substituents.

A simple and efficient strategy is proposed to significantly improve the antibacterial activity of peptaibols and other antimicrobial peptides by N-terminal capping with 1,2,3-triazole bearing various hydrophobic substituents on C-4. Such N-terminal insertions on alamethicin F50/5 could enhance its antimicrobial activity on Gram-positive bacteria without modification of its overall three-dimensional structure. Although the native peptide and its analogues shared comparable helical contents, the crystal structure of one of the most active derivative showed a local slight distortion of the N-terminal extremity, which was also observed in solution using NMR spectroscopy. Importantly, fluorescence studies showed that the N-capped derivatives had increased affinity for liposomes, which may indicate they interacted more strongly with the bacterial membrane than alamethicin F50/5.