Scalable Synthesis of All Stereoisomers of 2-Aminocyclopentanecarboxylic Acid─A Toolbox for Peptide Foldamer Chemistry.

Although the construction of peptides with well-defined three-dimensional structures and predictable functions, including biological activity, using conformationally constrained ß-amino acids has been shown to be a very successful strategy, their broad application is limited by access to the appropriate building blocks. In particular, trans- and cis-stereoisomers of 2-aminocyclopentanecarboxylic acid (ACPC) are of high interest. The scalable synthesis of all four stereoisomers of Fmoc derivatives of ACPC is presented with NMR-based analysis methods for their enantiomeric purity.

Hexa- and octanuclear copper(II) complexes with a tetraeicosaaza amine macrocycle.

One hexa- and two octanuclear Cu(II) complexes were synthesised from different metal salts and a very large (8 + 8) tetraeicosaaza macrocycle. These nitrate, chloride and sulphate coordination compounds were characterised by taking elemental analysis, spectroscopy, crystallography and magnetic susceptibility measurements. Their crystal structures revealed different interesting coordination modes of Cu(II) cations and nuclearity in these centrosymmetric complexes. For the sulphate complex two different, homo- vs. heterochiral, arrangements of the same macrocycle L3 around the same Cu(II) cations take place.

Crystallization as a selection force at the polymerization of nucleotides in a prebiotic context.

Accumulation and selection of nucleotides is one of the most challenging problems surrounding the origin of the first RNA molecules on our planet. In the current work we propose that guanosine 3',5' cyclic monophosphate could selectively crystallize upon evaporation of an acidic prebiotic pool containing various other nucleotides. The conditions of the evaporative crystallization are fully compatible with the subsequent acid catalyzed polymerization of this cyclic nucleotide reported in earlier studies and may be relevant in a broad range of possible prebiotic environments. Albeit cytidine 3',5' cyclic monophosphate has the ability to selectively accumulate under the same conditions, its crystal structure is not likely to support polymer formation.

SO3H-Functionalized Epoxy-Immobilized Fe3O4 Core-Shell Magnetic Nanoparticles as an Efficient, Reusable, and Eco-Friendly Catalyst for the Sustainable and Green Synthesis of Pyran and Pyrrolidinone Derivatives.

A SO3H-functionalized epoxy-immobilized Fe3O4 core-shell magnetic nanocatalyst was prepared through a simple three-step procedure, and it was identified by various analyses such as Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential thermal gravity (DTG), Brunauer-Emmett-Teller (BET) analysis, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), vibration sample magnetometry (VSM), and powder X-ray diffraction (PXRD). BET analysis showed that the as-prepared nanocatalyst was synthesized with a mesoporous structure and high specific area (35.45 m2 g-1). The TEM image clearly showed that the particle size distribution was in the range of 47-65 nm. The designed magnetic nanocatalyst was used successfully in the synthesis of pyran derivatives via the reaction of dimedone, malononitrile, and various aromatic aldehydes and synthesis of pyrrolidinone derivatives via the reaction of various aromatic aldehydes, aniline, and diethyl acetylenedicarboxylate. The nanocatalyst was simply isolated from the reaction mixture utilizing an external magnet and reused several times according to the model reactions without significant loss in its efficiency.

Multinuclear Ni(II) and Cu(II) complexes of a meso 6 + 6 macrocyclic amine derived from trans-1,2-diaminocyclopentane and 2,6-diformylpyridine.

Four hexanuclear chloride and sulphate Ni(II) and Cu(II) complexes 1, 2, 4 and 5 and one tetranuclear nitrate Cu(II) complex 3 have been synthesised from appropriate metal salts and 6 + 6 octadecaaza macrocyclic ligands. All obtained coordination compounds have been characterised by elemental analysis, spectroscopic methods (ESI MS, NMR and EPR), magnetic susceptibility measurements and X-ray crystallography. Their X-ray crystal structures reveal different coordination modes of metal cations involved in the obtained centro-symmetrical coordination compounds. The conformational folding of the macrocyclic ligand adopted in the respective complexes depends on the number of metal cations bound within the macrocycle but not on their type. The cavities of these multinuclear complexes might be occupied by solvent molecules and counter anions bound by hydrogen bonds or might be empty in the case where the macrocyclic ring of the ligand is squeezed in the middle. All obtained Ni(II) and Cu(II) coordination compounds are paramagnetic. This has been proved by their 1H NMR and EPR spectra and magnetic measurements. Direct current (DC) variable-temperature magnetic susceptibility measurements on the polycrystalline samples of 1-5 were carried out in the temperature range of 1.8-300 K. The magnetic behaviour of 1 and 2 is dominated by the magnetic anisotropy of the nickel(II) ion masking the magnetic interactions between magnetic centres. The magnetic data of 3-5 reveal small antiferromagnetic interactions within the Cu4 and Cu6 units. EPR experiments for 3-5 show, at 9.6 and 34 GHz frequencies, that the predominant contribution to the orbitals occupied by the unpaired electrons in the ground state originates from dx2-y2.

Controlling chirality in the synthesis of 4 + 4 diastereomeric amine macrocycles derived from trans-1,2-diaminocyclopentane and 2,6-diformylpyridine.

A few suitably long dialdehyde and primary diamine building blocks of a predetermined chirality have been designed and synthesized to enable controlled and efficient synthesis of all six possible diastereomers of 4 + 4 macrocyclic amine derived from trans-1,2-diaminocyclopentane (DACP) and 2,6-diformypyridine (DFP) units. Although two out of six diastereomers have been reported recently, their synthesis presented here is more direct and occurs with an improved yield. This family of 4 + 4 macrocycles contains one pair of homochiral enantiomers of identical RRRRRRRR and SSSSSSSS configurations of DACP units, two different meso forms (meso I of alternating RRSSRRSS and meso II of neighboring RRRRSSSS configuration of DACP moieties) as well as one pair of heterochiral enantiomers, where configuration of one diamine fragment is opposite to the other three diamine parts, RRRRRRSS and SSSSSSRR, respectively. The structures of each type of macrocycle in solid state have been confirmed by single crystal analyses of a macrocyclic amine in its suitable protonated form. The different symmetry of each type of macrocycle in solutions has been proved by 1H and 13C NMR spectra of their hydrochloride derivatives. The chiral nature of two different pairs of optically active enantiomers has been established by circular dichroism spectra. These chiral 4 + 4 diastereomeric macrocycles are receptors for chiral guests and recognize in solution 10-camphorsulfonic acid as well as chiral tartaric acid.

Sorting Phenomena and Chirality Transfer in Fluoride-Bridged Macrocyclic Rare Earth Complexes.

The reaction of fluoride anions with mononuclear lanthanide(III) and yttrium(III) hexaaza-macrocyclic complexes results in the formation of dinuclear fluoride-bridged complexes. As indicated by X-ray crystal structures, in these complexes two metal ions bound by the macrocycles are linked by two or three bridging fluoride anions, depending on the type of the macrocycle. In the case of the chiral hexaaza-macrocycle L1 derived from trans-1,2-diaminocyclohexane, the formation of these µ2-fluorido dinuclear complexes is accompanied by enantiomeric self-recognition of macrocyclic units. In contrast, this kind of recognition is not observed in the case of complexes of the chiral macrocycle L2 derived from 1,2-diphenylethylenediamine. The reaction of fluoride with a mixture of mononuclear complexes of L1 and L2, containing two different Ln(III) ions, results in narcissistic sorting of macrocyclic units. Conversely, a similar reaction involving mononuclear complexes of L1 and complexes of achiral macrocycle L3 based on ethylenediamine results in sociable sorting of macrocyclic units and preferable formation of heterodinuclear complexes. In addition, formation of these heterodinuclear complexes is accompanied by chirality transfer from the chiral macrocycle L1 to the achiral macrocycle L3 as indicated by CPL and CD spectra.

Magnetic Nanoparticles Functionalized with Copper Hydroxyproline Complexes as an Efficient, Recoverable, and Recyclable Nanocatalyst: Synthesis and Its Catalytic Application in a Tandem Knoevenagel-Michael Cyclocondensation Reaction.

A novel catalyst has been afforded by attaching of a Cu(proline)2 complex to magnetic nanoparticles through cheap, simple, and readily available chemicals. This catalyst was characterized by Fourier transform infrared, energy-dispersive X-ray, X-ray diffraction, vibrating-sample magnetometry, transmission electron microscopy, scanning electron microscopy, and inductively coupled plasma analyses. The catalytic activity of the Fe3O4@NH2@TCT@HProCu nanocatalyst was investigated in a green and effective synthesis of pyran derivatives in high yields by applying three-component reactions of malononitrile, dimedone, and aldehydes in ethanol. Conversion was high under optimal conditions. The obtained nanocatalyst could be easily separated from the mixture of the reaction and was recyclable nine times via a simple magnet without considerable reduction of its catalytic efficiency. Operational simplicity, high product yields, environmental friendliness, ecofriendliness, economical processing, and easy workup are the features of this methodology.

Crystal structures and phase transitions of imidazolium hypodiphosphates.

Two imidazolium hypodiphosphates, (C3H5N2)(H3P2O6) (I) and (C3H5N2)2(H2P2O6) (II), have been synthesized and structurally characterized. In both metal-free organic-inorganic hybrids (I) and (II), the hypodiphosphate mono- and dianions, (H3P2O6)- and (H2P2O6)2-, form hydrogen-bonded frameworks of different types, to which the organic cations are linked via N-H...O and C-H...O hydrogen bonds. The purity of the compounds was confirmed by powder X-ray diffraction. Differential scanning calorimetry of compound (I) revealed two structural phase transitions: continuous at 311.8 K [cooling/heating; from high-temperature phase (HTP) to room-temperature phase (RTP)] and a discontinuous one at 287.9/289.2 K [RTP → low-temperature phase (LTP)]. Compound (I) is characterized in a wide temperature range by single-crystal and powder X-ray diffraction methods. Crystal structures of high- and low-temperature phases are determined, which show orthorhombic (HTP, Pnna, No. 52) → monoclinic (LTP, P21/n11, No. 14, a-axis doubled) structural change on cooling with an intermediate incommensurately modulated phase (RTP). Dynamic properties of polycrystalline (I) were studied by means of dielectric spectroscopy. The dielectric behaviour is explained by the motion of imidazolium cations.

Dicarba[26]hexaporphyrinoids(1.1.1.1.1.1) with an Embedded Cyclopentene Moiety-Conformational Switching.

Invited for the cover of this issue is Lechoslaw Latos-Grazynski and co-workers at University of Wroclaw. The image depicts two essential conformations of 31,34-dicarba[26]hexachlorins: dumbbell and rectangular with regular or doubly inverted carbocyclic rings, respectively. Read the full text of the article at 10.1002/chem.202002603.

Dicarba[26]hexaporphyrinoids(1.1.1.1.1.1) with an Embedded Cyclopentene Moiety-Conformational Switching.

Incorporation of cyclopentene fragments into a skeleton of parental [26]hexaphyrin(1.1.1.1.1.1) afforded extended carbaporphyrinoids: 31,34-dicarbahexa[26]chlorin and its derivatives: the first externally substituted by ethoxy and 2,4,6-trimethylbenzylidene groups and the second one formed by selective oxidation of one cyclopentene ring. Macrocycles adopt dumbbell-shaped conformations with two meso hydrogen atoms located inside the macrocyclic cavity. Protonation of 31,34-dicarba[26]hexachlorins provided dications existing in dumbbell-shaped and rectangular conformations.

Mixed Macrocycles Derived from 2,6-Diformylpyridine and Opposite Enantiomers of trans-1,2-Diaminocyclopentane and trans-1,2-Diaminocyclohexane.

The condensation reaction of 2,6-diformylpyridine with an equimolar mixture of opposite enantiomers of trans-1,2-diaminocyclopentane and trans-1,2-diaminocyclohexane using a dynamic combinatorial chemistry approach has been examined. In nonmetal-templated reactions, depending on reaction conditions, mixed 2 + 1 + 1 macrocyclic imine or bigger mixed 4 + 2 + 2 imine macrocycle are formed selectively. The 2 + 1 + 1 imine used as a precursor in the templated by CdII ions produces a library of enlarged chiral mixed imines coordinated with metal cations among which the hexanuclear CdII complex of 6 + 3 + 3 imine was isolated and characterized. All macrocyclic imine compounds have been reduced to the corresponding macrocyclic amines, which have been further transformed into their hydrochlorides. Each macrocyclic compound has been obtained as two enantiomers. For imine macrocycles and for the hydrochloride derivatives of macrocyclic amines, their X-ray crystal structures have been determined. In particular, the crystals of protonated 4 + 2 + 2 macrocyclic amine, which contains two types of diastereomeric cations differing in terms of inverted twists of pyridine moieties, and hexanuclear CdII complex of 6 + 3 + 3 imine, which gives a deeper insight into the expansion reaction, have been investigated. A heterochiral self-sorting of 2 + 2 and 2 + 1 + 1 macrocyclic imines has been confirmed by a competition reaction of 2,6-diformylpyridine, racemic trans-1,2-diaminocyclopentane, and racemic trans-1,2-diaminocyclohexane and theoretical calculations.

Trinuclear and Hexanuclear Lanthanide(III) Complexes of the Chiral 3+3 Macrocycle: X-ray Crystal Structures and Magnetic Properties.

A new triphenolic hexaaza chiral macrocyclic amine L forms trinuclear complexes 1-3 with rare earth metal lanthanide(III) ions (Ln = Dy, Eu, and Y) with the general formula [Ln3L(µ3-OH)2(NO3)4(H2O)2]· xCH3OH. The crystal structures of the nitrate derivatives of this type reveal the presence of a {Ln3(µ3-OH)2} core within the macrocycle. For the chloride derivative of dysprosium(III) 4, a duplex of the trinuclear compound is formed to give the hexanuclear [Dy6L2(µ3-OH)3(µ3-O)(µ2-Cl)3Cl4(H2O)2] compound, in which two trinuclear macrocyclic units are linked by bridging chloride anions, supplemented by a hydrogen bond connecting the central oxo and hydroxo bridges as well as by weak interactions at the periphery of the macrocycle. The nuclear magnetic resonance spectra of these complexes reveal a dynamic behavior in solution related to exchange of axial ligands and hindered rotation of phenyl substituents. Magnetic studies of the nitrate (1-3) and chloride (4) dysprosium(III) complexes suggest the presence of weak ferromagnetic interactions between neighboring metal centers. The interaction is strongest for compound 1, and for the related duplex compound 4, it appears to be somewhat weaker. The ac susceptibility measurements for complexes 1 and 4 confirm their field-induced single-molecule magnet behavior with the following characteristics: Ueff = 10.6 cm-1 (15.2 K), τ0 = 2.05 × 10-4 s under 2500 Oe dc fields for 1; Ueff = 7.9 cm-1 (11.4 K), τ0 = 1.68 × 10-4 s under a 3000 Oe dc field for 4.

Low pH constructed Co(ii) and Ni(ii) 1D coordination polymers based on Cα-substituted analogues of zoledronic acid: structural characterization, and spectroscopic and magnetic properties.

Three novel coordination compounds based on α,α-disubstituted analogues of zoledronic acid with a cyclopropane (cpp) or cyclobutane (cbt) ring on the Cα carbon, isomorphous [Co(H2cppZol)(H2O)]·H2O (1a), [Ni(H2cppZol)(H2O)]·H2O (1b) and [Co(H2cbtZol)(H2O)]·H2O (2a), were synthesized under hydrothermal conditions at low pH. Single-crystal X-ray diffraction analysis revealed that all the compounds had a 1D double zig-zag chain architecture with an 8 + 8 ring motif formed by alternately arranged symmetrical (-O-P-O-)2 bridges linking equivalent octahedral metal centres. Both the ligand coordination mode and chain architecture displayed by 1a, 1b and 2a are unique among 1D [M(H2L)(H2O) x ]·yH2O coordination polymers based on nitrogen-containing bisphosphonates reported so far. All the compounds exhibit similar decomposition pathways upon heating with thermal stabilities decreasing in the order 1b > 1a > 2a. The IR spectra revealed that lattice water release above 227, 178 and 97 °C, respectively, does not change the chain architecture leaving them intact up to ca. 320, 280 and 240 °C. Magnetic behaviour investigations indicated that 1a, 2a and 1b exhibit weak alternating antiferromagnetic-ferromagnetic exchange interactions propagated between the magnetic centres through double (-O-P-O-)2 bridges. The boundary between antiferro- and ferromagnetic couplings for the Co-O⋯O-Co angle in 1a and 2a was estimated to be ca. 80°. This value is also applicable for recently reported [M3(HL)2(H2O)6]·6H2O (M = Co, Ni) complexes based on α,α-disubstituted analogues of zoledronic acid and can be used to the explain magnetic behaviour of 1b.

Vinylphosphonium Salt-Mediated Reactions: A One-Pot Condensation Approach for the Highly cis-Selective Synthesis of N-Benzoylaziridines and the Green Synthesis of 1,4,2-Dioxazoles as Two Important Classes of Heterocyclic Compounds.

An efficient, one-pot, and convenient approach for the reaction of the same precursors, trialkyl(aryl) phosphines, acetylene diesters, and benzhydroxamic acids has been developed to produce two important classes of heterocyclic compounds: N-benzoylaziridines and 1,4,2-dioxazoles. The strategy utilizes the intermediate solvation as a key step in product selectivity. The usefulness of the developed approach has been confirmed in the unprecedented highly cis-selective formation of the N-benzoylaziridines. In addition, the procedure provides a green alternative method for the synthesis of 1,4,2-dioxazoles employing a ß-cyclodextrin nanoreactor in aqueous media.

Chiral Cryptates Derived from a Hexaazamacrocycle.

The reactions of hexaazamacrocycle 1 with 2,6-bis(bromomethyl)pyridine or 2,6-bis[(tosyloxy)methyl)]pyridine in the presence of appropriate carbonates result in the formation of derivatives of cryptand 6: enantiopure azacryptates of sodium and potassium. Crystal structures of these compounds indicate interaction of a metal ion with four pyridine nitrogen atoms and four tertiary amine atoms. The competition reactions monitored by NMR spectroscopy indicate preferential binding of Na+ over K+ as well as higher affinity of 6 for Na+ in comparison with the [2.2.1] cryptand.

The first protection-free synthesis of magnetic bifunctional l-proline as a highly active and versatile artificial enzyme: Synthesis of imidazole derivatives.

l-Proline is a bifunctional versatile organocatalyst that could promote a variety of useful transformations. Some passive and dynamic interactions between this simple amino acid and different substrates, which are necessary to enzymatic reactions, have given it "the simplest enzyme" title. Herein we presented the first report on the synthesis of magnetic bifunctional l-proline as an artificial enzyme without requiring any protection/deprotection steps according to an operationally simple process. This magnetic nano-biocatalyst is a promising catalyst that in a case study was successfully applied for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles in the 70-99% and 60-90% yields respectively, which it could be extended to the variety of l-proline-based organic transformations. The synergic effect of bifunctional l-proline shell as catalytic active site and magnetite nanoparticles core, which could function as protein mimics endow it high efficiency, versatility, recoverability, reusability and good turnover frequency, which are necessary characters for artificial enzymes' designing.

Hexanuclear and Trinuclear Metal Complexes of a Giant Octadecaaza Macrocycle.

A large macrocyclic ligand containing six pyridine fragments and six diaminocyclopentane fragments is able to form hexanuclear Zn(II) and Ni(II) complexes as well as a trinuclear Zn(II) complex. X-ray crystal structures of these complexes indicate quite different ligand conformations. In the hexanuclear Zn(II) derivative with chloride counteranions metal ions have a distorted-trigonal-bipyramidal geometry and occupy loop sections formed by the highly folded macrocycle, which adopts a globular shape. In the hexanuclear Ni(II) derivative with nitrate counteranions metal ions exhibit a distorted-octahedral geometry and the ligand conformation is much more open, while in the trinuclear Zn(II) complex the macrocycle wraps around the octahedral metal ions. The last highly entangled conformation of the trinuclear complex is also present in solution, as confirmed by the NOESY spectra. The NMR data indicate that the hexanuclear Zn(II) complex partially dissociates in water solutions to form the trinuclear complex, while the 1H NMR titration of the free macrocycle with zinc(II) chloride indicates that the formation of a trinuclear complex corresponds to cooperative binding of metal ions.

Two isomorphous Co(ii) coordination polymers based on new α,α-disubstituted derivatives of zoledronic acid: synthesis, structures and properties.

Two novel α,α-disubstituted derivatives of zoledronic acid, namely 1-hydroxy-2-(1H-imidazol-1-yl)-2-methylpropylidene-1,1-diphosphonic acid (H4L1) and 1-hydroxy-2-[1-(1H-imidazol-1-yl)cyclopropyl]ethylidene-1,1-diphosphonic acid (H4L2) were synthesized and structurally characterized by single-crystal X-ray diffraction. The reaction of cobalt acetate with H4L1 and H4L2 carried out under hydrothermal conditions afforded two isomorphous Co3(HL1)2(H2O)6·6H2O (1a) and Co3(HL2)2(H2O)6·6H2O (2a) complexes. Both compounds are characterized by means of X-ray crystallography, IR and NIR-Vis-UV spectroscopic methods. Furthermore, their magnetic properties and thermal stabilities are reported. The crystals of 1a and 2a feature infinite 1D polymeric chains built from alternately arranged dinuclear [Co2(HL1/HL2)(H2O)2]2 units and {Co1O6} octahedra running along the [1[combining macron]10] crystallographic direction. In both compounds, crystallographically distinct Co1 and Co2 atoms are six-coordinated. As is reflected in T values (T - index of tetragonality), the coordination environment of Co1 generates a slightly elongated octahedron (T = 0.94), whereas a slightly compressed octahedron (T = 1.06 for 1a and 1.05 for 2a) is formed around Co2. An assumption that the d-d type absorption is mainly attributed to the inversion related Co2 centers, whose population is two times higher than that of Co1, afforded a good correlation between calculated transition energies and experimental NIR-Vis-UV spectra. The magnetic susceptibility measurements analyzed in terms of a spin-3/2 Heisenberg trimer chain revealed that Co1Co2 interactions within the trimer are antiferromagnetic whereas Co2Co2 intertrimer interactions are ferromagnetic.

A Three-Component Reaction for the Synthesis of 1-Azabicyclo[3.1.0]hexane-3-enes.

A novel and simple synthesis of 1-azabicyclo[3.1.0]hexane-3-ene derivatives is described. The synthesis is carried out via a simple three-component reaction between aryl aldehydes, malononitrile, and hydroxylamine hydrochloride in water. Eco-friendliness, excellent product yields, short reaction time, inexpensive and readily available starting materials, and interesting reaction and products are the main advantages of this method.