Polymorph 2b Research Articles

Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.

Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, eLife 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability.

Dependence of Absorption and Emission Spectra on Polymorphs of Gold(I) Isocyanide Complexes: Theoretical Study with QM/MM Approach

We theoretically investigated phenyl(phenyl isocyanide) gold(I) (PhNC)Au(Ph) 1 and phenyl(dimethylphenyl isocyanide) gold(I) (dimPhNC)Au(Ph) 2 in crystal using our periodic quantum mechanics/molecular mechanics (QM/MM) method based on the self-consistent point charges to elucidate interesting mechano-chemical changes of absorption and emission spectra of 1 and 2 in crystal. To characterize 1 and 2 in crystal, their absorption and emission spectra in crystal were compared to those in gas phase and CHCl3 solvent, where a three-dimensional reference interaction site model self-consistent field (3D-RISM-SCF) was employed to incorporate solvation effect. To investigate the phosphorescence spectrum in crystal, we optimized the geometry of the molecule at the triplet state in crystal which had ground-state geometry because the population of the excited state is generally very small. The QM/MM calculations showed that 1 formed two polymorphs 1b and 1y, 2 formed two polymorphs 2b and 2g, and 1y was more stable tha...

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds - an experimental and theoretical study.

The dispersion type Bi···π arene interaction is one of the important structural features in the assembly process of arylbismuth compounds. Several triarylbismuth compounds and polymorphs are discussed and compared based on the analysis of single crystal X-ray diffraction data and computational studies. First, the crystal structures of polymorphs of Ph3Bi (1) are described emphasizing on the description of London dispersion type bismuth···π arene interactions and other van der Waals interactions in the solid state and the effect of it on polymorphism. For comparison we have chosen the substituted arylbismuth compounds (C6H4-CH═CH2-4)3Bi (2), (C6H4-OMe-4)3Bi (3), (C6H3-t-Bu2-3,5)3Bi (4) and (C6H3-t-Bu2-3,5)2BiCl (5). The structural analyses revealed that only two of them show London dispersion type bismuth···π arene interactions. One of them is the styryl derivative 2, for which two polymorphs were isolated. Polymorph 2a crystallizes in the orthorhombic space group P212121, while polymorph 2b exhibits the monoclinic space group P21/c. The general structure of 2a is similar to the monoclinic C2/c modification of Ph3Bi (1a), which leads to the formation of zig-zag Bi–arenecentroid ribbons formed as a result of bismuth···π arene interactions and π···π intermolecular contacts. In the crystal structures of the polymorph 2b as well as for 4 bismuth···π arene interactions are not observed, but both compounds revealed C–HPh···π intermolecular contacts, as likewise observed in all of the three described polymorphs of Ph3Bi. For compound 3 intermolecular contacts as a result of coordination of the methoxy group to neighboring bismuth atoms are observed overruling Bi···π arene contacts. Compound 5 shows a combination of donor acceptor Bi···Cl and Bi···π arene interactions, resulting in an intermolecular pincer-type coordination at the bismuth atom. A detailed analysis of three polymorphs of Ph3Bi (1), which were chosen as model systems, at the DFT-D level of theory supported by DLPNO-CCSD(T) calculations reveals how van der Waals interactions between different structural features balance in order to stabilize molecular arrangements present in the crystal structure. Furthermore, the computational results allow to group this class of compounds into the range of heavy main group element compounds which have been characterized as dispersion energy donors in previous work.

Polymorphs of Thiazole-Derived Imines Connected to Hydroxyaromatics

Conformational polymorphs arising from C–N bond rotation of a methylthiazole ring anchored to a nitrogen atom, which is a constituent of a six-membered intramolecularly hydrogen-bonded system, are studied. We have observed two polymorphs each from 2-(E)-[(5-methylthiazol-2-ylimino)methyl]phenol (1) and 1-(E)-[(5-methylthiazol-2-ylimino)methyl]unaphthalen-2-ol (2). Individual polymorphs are distinguished on the basis of their packing patterns and orientations of functional groups. One polymorph of compound 2, namely polymorph 2b, having Z′ = 2, is metastable; this polymorph is generated on heating of polymorph 2a, which has Z′ = 1.

Crystal Structure and Hirshfeld Surface Analysis of 1,2-Bis((2-(Bromomethyl)Phenyl)Thio)Ethane and Two Polymorphs of 1,2-Bis((2-((Pyridin-2-ylthio)Methyl)Phenyl)Thio)Ethane

1,2-Bis((2-(bromomethyl)phenyl)thio)ethane (1) and 1,2-bis((2-((pyridin-2-ylthio)methyl)phenyl)thio)ethane (2) were prepared and characterized by IR and NMR spectroscopy and single-crystal X-ray crystallography. X-ray diffraction studies shown that compound 1 crystallizes in a monoclinic space group P21/n with crystal parameters a=8.3970(3) A, b=12.4566(2) A, c=8.9251(3) A; β=117.911(3)°, V=824.96(5) A3 and z=2, and compound 2 exists in two monoclinic polymorphs (2a and 2b). Polymorph 2a crystals are in space group P21, with unit cell parameters a=5.3702(2) A, b=14.4235(6) A, c=15.4664(7) A, β=119.97(9)°, V=1197.97(9) A3 and z=2, while polymorph 2b crystals are in space group P21/c with unit cell parameters a=7.8312(3) A, b=9.6670(4) A, c=16.2962(5) A, β=121.219(3)°; V=1210.12(7) A3 and z=2. Variations in the crystal packing help to distinguish these two polymorphs via π-π and C−H•••π interactions. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots have been performed to gain insight into the behavior of these interactions in compound 1 and polymorphs 2a and 2b.

Metastable polymorphic form of isopropylbenzophenone derivative directly obtained by the solid-state photoreaction investigated by ab initiopowder X-ray diffraction analysis

The crystalline state of 2-(2,4,6-triisopropybenzoyl)((S)-1-phenylethyl)benzamide (1) is known to undergo a diastereospecific Norrish type II photocyclization under UV irradiation, giving a single photoproduct (R,S)-cyclobutenol (2). Its polycrystalline form (2A) has a different X-ray diffraction pattern from the known polymorph 2B, which is obtained from recrystallization of the photoproduct. Such a polymorphic phenomenon, which is the result of a solid-state photoreaction, is, in itself, highly interesting and the structure of the photoproduct 2A should directly lead to the photoreaction mechanism. Thus, the crystal structure of 2A has been directly determined from the powder X-ray diffraction data. Interestingly, the crystal packing has been retained during the photoreaction process and, although the powder X-ray diffraction pattern is significantly different, there are only minor structural changes. The comparison of the crystal structures of 1 and 2A reveals the photoreaction mechanism. The lattice energy calculations of the polymorphic forms of 2A and 2B reveals that 2A, which is obtained only by the solid-state photoreaction, is less stable than 2B, which is why it is not reformed on recrystallization.

Conformational morphosis in azocalix[4]arenes

The first example of cesium induced chemical morphosis of new azocalix[4]arene 2 is described. It has been observed that pyridylazocalix[4]arene 2a selectively reacts with cesium ion to yield a new polymorph 2b. The synthesized polymorphs (2a and 2b) have similar gross conformational structures which profoundly differ at supramolecular level to exhibit a ‘hand-shake’ arrangement with respect to pyridyl units or π–π interaction of phenolic units.

S = (3)/(2) S = (1)/(2) spin crossover behavior in five-coordinate halido- and pseudohalido-bis(o-iminobenzosemiquinonato)iron(III) complexes.

Five-coordinate halido- and pseudohalido-bis(o-iminobenzosemiquinonato)iron(III) complexes [Fe(III)X(L(ISQ))(2)] (X = Cl(-) (1), Br(-) (2a, 2b), I(-) (3), N(3)(-) (4), and NCS(-) (5)) have been synthesized where (L(ISQ))(1)(*)(-) represents the pi radical anion N-phenyl-o-imino(4,6-di-tert-butyl)benzosemiquinonate(1-). The molecular structures of the two polymorphs 2a and 2b have been determined at 100, 220, and 295 K, respectively, by single crystal X-ray crystallography. Variable temperature magnetic susceptibility data reveal the following electronic ground states, S(t): For 1, it is (3)/(2). Polymorph 2a contains a 1:1 mixture of (3)/(2) and (1)/(2) forms in the range 4.2 to approximately 150 K; above 150 K the latter form undergoes a spin crossover (1)/(2) --> (3)/(2). Polymorph 2b contains only the S(t) = (3)/(2) form (4-300 K). Complex 3 contains the S(t) = (1)/(2) form in the range 4-130 K, but above 130 K, a spin crossover to the (3)/(2) form is observed which is confirmed by three crystal structure determinations at 100, 220, and 295 K. Complex 4 possesses an S(t) = (1)/(2) ground state at 80 K and undergoes a spin crossover at higher temperatures. Complex 5 has a temperature-independent S(t) = (3)/(2) ground state. All crystal structures of 1, 2a, 2b, 3, 4, and 5, regardless at which temperature the data sets have been measured, show that two o-iminobenzosemiquinonate(1-) pi radical anions are N,O-coordinated in all of these neutral iron complexes. The Fe-N and Fe-O bond distances are longer in the S(t) = (3)/(2) and shorter in the S(t) = (1)/(2) forms. The S(t) = (3)/(2) ground state is attained via intramolecular antiferromagnetic coupling between a high spin ferric ion (S(Fe) = (5)/(2)) and two ligand pi radicals whereas the S(t) = (1)/(2) form is generated from exchange coupling between an intermediate spin ferric ion (S(Fe) = (3)/(2)) and two ligand radicals.