6‐Chloroisocytosine and 5‐bromo‐6‐methylisocytosine: again,one or two tautomers present in the same crystal?

It is well known that pyrimidin‐4‐one derivatives are able to adopt either the 1H‐ or the 3H‐tautomeric form in (co)crystals, depending on the coformer. As part of ongoing research to investigate the preferred hydrogen‐bonding patterns of active pharmaceutical ingredients and their model systems, 2‐amino‐6‐chloropyrimidin‐4‐one and 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4‐one have been cocrystallized with several coformers and with each other. Since Cl and Br atoms both have versatile possibilities to interact with the coformers, such as via hydrogen or halogen bonds, their behaviour within the crystal packing was also of interest. The experiments yielded five crystal structures, namely 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (1/3), C₅H₇N₂⁺·C₄H₃ClN₃O⁻·3C₄H₄ClN₃O, (Ia), 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one–2‐aminopyridine (2/10/1), 2C₅H₇N₂⁺·2C₄H₃ClN₃O⁻·10C₄H₄ClN₃O·C₅H₆N₂, (Ib), the solvent‐free cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one (1/1), C₅H₆BrN₃O·C₅H₆BrN₃O, (II), the solvate 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–N‐methylpyrrolidin‐2‐one (1/1/1), C₅H₆BrN₃O·C₅H₆BrN₃O·C₅H₉NO, (III), and the partial cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (0.635/1/0.365), C₅H₆BrN₃O·C₅H₆BrN₃O·C₄H₄ClN₃O, (IV). All five structures show R₂²(8) hydrogen‐bond‐based patterns, either by synthon 2 or by synthon 3, which are related to the Watson–Crick base pairs.     

2‐Halogeno‐1,3,2‐diazaarsolenes and 2‐halogeno‐1,3,2‐diazastibolenes: Examples for spontaneous E?X bond heterolysis or not?

2‐X‐1,3,2‐diazaarsolenes and 2‐X‐1,3,2‐ stibolenes (X = Cl, Br) were prepared from appropriate α‐amino‐aldimine precursors via transamination with ClSb(NMe₂)₂ or via base‐induced dehydrohalogenation with EX₃ (E = As, Sb). The products were further converted into 2‐iodo‐derivatives via halide exchange with Me₃SiI, or into 1,3,2‐diazaarsolenium or 1,3,2‐stibolenium salts via halide abstraction using E′X₃ (E′ = Al, Ga, Sb) or Me₃SiOTf. All compounds synthesized were characterized by spectroscopic data and several of them by single‐crystal X‐ray diffraction studies. The results of these investigations confirmed that diazaarsolenium or stibolenium cations are stabilized by similar π‐delocalization effects as the corresponding diazaphospholenium cations. 2‐Halogeno‐1,3,2‐diazaarsolenes and 2‐halogeno‐132‐stibolenes are best addressed as molecular species whose covalent E X bonds are as in 2‐chloro‐diazaphospholenes weakened by intramolecular π(C₂N₂) → σ*(E X) and, in the case of the Sb‐containing heterocycles, inter‐ molecular n(X′) → σ*(E X) hyperconjugation between the σ* (E X) orbital and a lone‐pair of electrons on the halogen atom of a neighboring molecule. Correlation of structural and spectroscopic data and the evaluation of halide transfer reactions allowed to conclude that the extent of E X bond weakening in the 2‐X‐substituted heterocycles decreases and thus the Lewis acidity of the cations increases, with increasing atomic number of the pnicogen atom. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:327–338, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20098     

Microwave Accelerated Polymerization of 2‐Phenyl‐2‐oxazoline: Microwave or Temperature Effects?

Summary: Investigations regarding the cationic ring‐opening polymerization of 2‐phenyl‐2‐oxazoline under microwave irradiation and conventional heating are reported. This study was inspired by contradictory reports of the (non‐)existence of non‐thermal microwave effects that might accelerate the cationic ring‐opening of 2‐oxazolines. The polymerization of 2‐phenyl‐2‐oxazoline was investigated under pressure in acetonitrile and under reflux (or at the boiling point of butyronitrile in a closed vessel) in butyronitrile utilizing a single‐mode microwave reactor and automated synthesis robots with conventional heating.

     

Which One is Bulkier: The 3,5‐Dimethylphenyl or the 2,6‐Dimethylphenyl Group? Development of Size‐Complementary Molecular and Macromolecular [2]Rotaxanes

We developed novel size‐complementary molecular and macromolecular rotaxanes using a 2,6‐dimethylphenyl terminal group as the axle‐end‐cap group in dibenzo‐24‐crown‐8‐ether (DB24C8)‐based rotaxanes, where the 2,6‐dimethylphenyl group was found to be less bulky than the 3,5‐dimethylphenyl group. A series of molecular and macromolecular [2]rotaxanes that bear a 2,6‐dimethylphenyl group as the axle‐end‐cap were synthesized using unsubstituted and fluorine‐substituted DB24C8. Base‐induced decomposition into their constituent components confirmed the occurrence of deslipping, which supports the size‐complementarity of these rotaxanes. The deslipping rate was independent of the axle length but dependent on the DB24C8 substituents. A kinetic study indicated the rate‐determining step was that in which the wheel is getting over the end‐cap group, and deslipping proceeded via a hopping‐over mechanism. Finally, the present deslipping behavior was applied to a stimulus‐degradable polymer as an example for the versatile utility of this concept in the context of stimulus‐responsive materials.     

Isostructural or not? Adducts of some aryl­tin halides with (E)‐1,2‐bis(4‐pyridyl)­ethene

The title complexes [μ‐(E)‐4,4′‐(ethene‐1,2‐diyl)­di­pyridine‐κ²N:N′]­bis­[halotris(4‐methyl­phenyl)­tin(IV)], [Sn₂(C₇H₇)₆X₂(C₁₂H₁₀N₂)], where halo is chloro (X = Cl) and bromo (X = Br) are isostructural. In both crystals, the mol­ecules lie on inversion centers, and there are voids of ca 80 ų that could, but apparently do not, accommodate water mol­ecules. The corresponding iodo structure (X = I) is almost, but not quite, isostructural with the other two compounds; when Br is changed to I, the length of the c axis decreases by more than 1 Å and the voids are no longer large enough to accomodate any solvent mol­ecule. The related complex [μ‐(E)‐4,4′‐(ethene‐1,2‐diyl)­di­pyridine‐κ²N:N′]­bis­[chloro­tri­phenyl­tin(IV)], [Sn₂(C₆H₅)₆Cl₂(C₁₂H₁₀N₂)], crystallizes in a related structure, but the mol­ecules lie on general rather than on special positions. The molecular structures of the four complexes are similar, but the conformation of the phenyl derivative is approximately eclipsed rather than staggered.     

Rydberg or Valence? The Long‐Standing Question in the UV Absorption Spectrum of 1,1′‐Bicyclohexylidene

The electronic excited states of the olefin 1,1′‐bicylohexylidene (BCH) are investigated using multiconfigurational complete active space self‐consistent‐field second order perturbation theory in its multi‐state version (MS‐CASPT2). Our calculations undoubtedly show that the bulk of the intensity of the two unusually intense bands of the UV absorption of BCH measured with maxima at 5.95 eV and 6.82 eV in the vapor phase are due to a single ππ* valence excitation. Sharp peaks reported in the vicinity of the low‐energy feature in the gas phase correspond to the beginning of the π3s_R Rydberg series. By locating the origin of the ππ* band at 5.63 eV, the intensity and broadening of the observed bands and their presence in solid phase is explained as the vibrational structure of the valence ππ* transition, which underlies the Rydberg manifold as a quasi‐continuum.     

Planar or nonplanar: what is the structure of urea in aqueous solution?

A combined quantum chemical statistical mechanical method has been used to study the solvation of urea in water, with emphasis on the structure of urea. The model system consists of three parts: a Hartree-Fock quantum chemical core, 99 water molecules described with a polarizable force-field, and a dielectric continuum. A free-energy profile along the transition of urea from planar to a nonplanar structure is calculated. This mode in aqueous solution is found to be floppy. That is, the structure of urea in water is not well-defined because the planar to nonplanar transition requires an energy of the order of the thermal energy at room temperature. We discuss the implications of this finding for simulation studies of urea in polar environments like water and proteins.     

Multicenter Homogeneous Dendritic Catalysts: The Higher the Generation,the Better the Reactivity and Selectivity? – A Comparative Study of the Catalytic Efficiency of Dendrimeric [1,1′‐Binaphthalene]‐2,2′‐diol‐Derived Catalysts

The G0 and G1 generations of optically active, multicenter 1,1′‐binaphthalene‐based dendritic ligands 4 and 5 constructed on a rigid oligo(arylene) framework were prepared by divergent synthesis. Their corresponding aluminum complexes 1 and 2 , respectively, were shown to possess slightly better reactivity and enantioselectivity than those of a monomeric 1,1′‐binaphthalene catalyst 3 in the Diels–Alder reaction between cyclopentadiene and 3‐[(E)‐but‐2‐enoyl]‐oxazolidin‐2‐one.     

Is the μ‐Oxo‐μ‐Peroxodiiron Intermediate of a Ribonucleotide Reductase Biomimetic a Possible Oxidant of Epoxidation Reactions?

Density functional calculations on a mu-oxo-mu-peroxodiiron complex (1) with a tetrapodal ligand BPP (BPP=N,N-bis(2-pyridylmethyl)-3-aminopropionate) are presented that is a biomimetic of the active site region of ribonucleotide reductase (RNR). We have studied all low-lying electronic states and show that it has close-lying broken-shell singlet and undecaplet (S=0, 5) ground states with essentially two sextet spin iron atoms. In strongly distorted electronic systems in which the two iron atoms have different spin states, the peroxo group moves considerably out of the plane of the mu-oxodiiron group due to orbital rearrangements. The calculated absorption spectra of (1,11)1 are in good agreement with experimental studies on biomimetics and RNR enzyme systems. Moreover, vibrational shifts in the spectrum due to (18)O(2) substitution of the oxygen atoms in the peroxo group follow similar trends as experimental observations. To identify whether the mu-oxo-mu-1,2-peroxodiiron or the mu-oxo-mu-1,1-peroxodiiron complexes are able to epoxidize substrates, we studied the reactivity patterns versus propene. Generally, the reactions are stepwise via radical intermediates and proceed by two-state reactivity patterns on competing singlet and undecaplet spin state surfaces. However, both the mu-oxo-mu-1,2-peroxodiiron and mu-oxo-mu-1,1-peroxodiiron complex are sluggish oxidants with high epoxidation barriers. The epoxidation barriers for the mu-oxo-mu-1,1-peroxodiiron complex are significantly lower than the ones for the mu-oxo-mu-1,2-peroxodiiron complex but still are too high to be considered for catalytic properties. Thus, theory has ruled out two possible peroxodiiron catalysts as oxidants in RNR enzymes and biomimetics and the quest to find the actual oxidant in the enzyme mechanism continues.     

What is the structure of the RecA-DNA filament?

The bacterial RecA protein has been a model system for understanding how a protein can catalyze homologous genetic recombination. RecA-like proteins have now been characterized from many organisms, from bacteriophage to humans. Some of the RecA-like proteins, including human RAD51, appear to function as helical filaments formed on DNA. However, we currently have high resolution structures of inactive forms of the protein, and low resolution structures of the active complexes formed by RecA-like proteins on DNA in the presence of ATP or ATP analogs. Within a crystal of the E. coli RecA protein, a helical polymer exists, and it has been widely assumed that this polymer is quite similar to the active helical filament formed on DNA. Recent developments have suggested that this may not be the case.     

Where is the Oxygen? Structural Analysis of α‐Humulene Oxidation Products by the Crystalline Sponge Method

Crystal structures of α‐humulene, a cyclic sesquiterpene, and its oxidized subproducts, were analyzed by the crystalline sponge method. Regio‐ and stereochemistry, including absolute configuration when a chiral oxidant was applied, and the stable conformations of all the scaffold‐related compounds were successfully determined for samples on a 5–50 μg scale.