ESR. Spectra and Structures of Radical Anions in the Dibenzo[a,e]cyclooctene Series

ESR. studies are reported for the radical anions of 5,6-didehydro- and 5,6,11,12-tetradehydro-dibenzo[a,e]cyclooctene (III and IV, resp.), in addition to that of dibenzo[a,e]cyclooctene (II) itself, the spectrum of which has been reexamined. Comparison of the proton and ¹³C coupling constants for II·?, III·? and IV·? indicates that the three radical anions do not differ greatly in their electronic and molecular structures. This statement implies that II·? should also be substantially planar, i.e., the tub-shaped eight-membered ring in II is expected to flatten on passing from the neutral molecule to its radical anion. Support for postulating such a change in geometry, analogous to that encountered with the parent cyclooctatetraene (I), is provided by INDO calculations.     

Li2H4I2O10, das erste Tetrahydrogendimesoperiodat

Li₂H₄I₂O₁₀, the First Tetrahydrogendimesoperiodate Li₂H₄I₂O₁₀ has been obtained as an intermediate during the dehydration of LiH₄IO₆ · H₂O to LiIO₄, for the first time. According to the results of an X-ray structure determination (monoclinic, P2₁/n, a = 533.98(4), b = 471.85(4), c = 1431.48(10) pm, β = 91.614(7)°, Z = 2, 726 diffractometer data, R = 0.056), Li₂H₄I₂O₁₀ contains the previously unknown tetrahydrogendimesoperiodate ion H₄I₂O₁₀^2?, consisting of two edge-shared IO₆ octahedra. They are connected with LiO₆ octahedra via common edges and vertices. The crystals are non-merohedrally twinned along (100).     

Eine neue Aminoazirin-Reaktion. Bildung von 3,6-Dihydropyrazin-2(1H)-onen

A New Aminoazirine Reaction. Formation of 3,6-Dihydropyrazin-2(1H)-ones The reaction of 3-(dimethylamino)-2H-azirines 1 and 2-(trifluoromethyl)-1,3-oxazol-5(2H)-ones 5 in MeCN or THF at 50–80° leads to 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 6 (Scheme 3). Reaction mechanisms for the formation of 6 are discussed: either the oxazolones 5 react as CH-acidic heterocycles with 1 (Scheme 4), or the azirines 1 undergo a nucleophilic attack onto the carbonyl group of 5 (Scheme 6). The reaction via intermediate formation of N-(trifluoroacetyl)dipeptide amide 8 (Scheme 5) is excluded.     

Engineering novel bioactive mini-proteins from small size natural and de novo designed scaffolds

Mini-proteins, polypeptides containing less than 100 amino acids, such as (animal toxins, protease inhibitors, knottins, zinc fingers, etc.) represent successful structural solutions to the need to express a specific binding activity in different biological contexts. Artificial mini-proteins have also been designed de novo, representing simplified versions of natural folds and containing natural or artificial connectivities. Both systems have been used as structural scaffolds in the engineering of novel binding activities, according to three main approaches: i) incorporation of functional protein epitopes into structurally compatible regions of mini-protein scaffolds; ii) random mutagenesis and functional selection of particular structural regions of mini-protein scaffolds; iii) minimization of protein domains by the use of sequence randomization and functional selection, combined with structural information, in an iterative process. These newly engineered mini-proteins, with specific and high binding affinities within a small size and well-defined three-dimensional structure, represent novel tools in biology, biotechnology and medical sciences. In addition, some of them can also be directly used in therapy or present high potential to serve as drugs. In all cases, they represent precious structural intermediates useful to identify frameworks for peptidomimetic design or directly lead to new small organic structures, representing novel drug candidates. The engineering of novel functional mini-proteins has the potential to become a fundamental step towards the conversion of a protein functional epitope or a flexible peptide lead into a classical pharmaceutical.     

Novel UDP-glycal derivatives as transition state analogue inhibitors of UDP-GlcNAc 2-epimerase

The "epimerisation" of UDP-GlcNAc to ManNAc, the first step in the biosynthesis of sialic acids, is catalyzed by UDP-GlcNAc 2-epimerase. In this paper we report the synthesis of transition state based inhibitors of this enzyme. To mimic the assumed first transition state of this reaction (TS 1), we designed and synthesized the novel UDP-exo-glycal derivatives 1-4. We also report herein the synthesis of 5 and 6, the first C-glycosidic derivatives of 2-acetamidoglucal, and the synthesis of the ketosides 7 and 8, which were designed as bis-substrate analogue and bis- product analogue, respectively, to mimic the second step of the reaction via the assumed second transition state TS 2.     

Additivity of the proton affinity of polysubstituted benzenes: the ipso position

It is shown, by the MP2(fc)/6-31G^{* *}/ /HF/6-31G^* +ZPE(HF/6-31G^*) theoretical model and concomitant use of homodesmic reactions, that the ipso proton affinities in polyfluorinated benzenes follow a simple additivity rule. Performance of the latter is good, as evidenced by a low average absolute deviation Δ_abs = 0.8 kcal/mol from the accurate ab initio results. Additional evidence supporting the additivity concept is provided by good accordance with the experimental proton affinity (PA) for perfluorobenzene. The present approach enables estimates of the ipso PAs of multiply substituted aromatics. It is particularly useful in those systems which involve or atomic groupings with lone pairs of electrons proximate to the aromatic π moiety. The additivity rule of thumb offers a simple rationalization of the ipso proton affinities. The origin of the PA additivity is briefly discussed.     

Structural Basis for Recognition of Guanosine by a Synthetic Tricyclic Cytosine Analogue: Guanidinium G‐Clamp

An oligonucleotide analogue containing a novel heterocyclic analogue, the guanidinium G‐clamp, was designed to allow formation of five H‐bonds to guanosine. The guanidinium group was introduced postsynthetically by treatment of the deprotected oligonucleotide containing a free amino group with a solution of 1H‐pyrazole‐1‐carboxamidine and purified by a combination of size‐exclusion chromatography and reversed‐phase HPLC. A single incorporation of this modification into an oligodeoxynucleotide sequence was found to increase duplex stability by 13° and 16° per modification to RNA and DNA, respectively. Crystals of a self‐complementary decamer sequence containing this modification were grown and diffracted to 1‐Å resolution. The structure was solved by molecular replacement and revealed that the modification forms additional H‐bonds to O(6) and N(7) of guanosine through the amino and imino N‐atoms, respectively. The origins of enhanced duplex stability are also attributed to increased stacking interactions mediated by the phenoxazine moiety of the G‐clamp and formation of H‐bond networks between the positively charged guanidinium group, H₂O molecules, and negatively charged O‐atoms from phosphates on the adjacent strand.     

New cationic aryldiazo,aryldiimine and arylhydrazine complexes of platinum

The preparation of some new cationic aryldiazo complexes of platinum of formula trans-[Pt(N₂Ar)(PEt₃)₂L]⁺, where N₂Ar = N₂C₆H₄F-m or -p and L = NH₃, Py, Et₃P or EtNC, is described. Protonation of these complexes gives the corresponding aryldiimide complexes trans-[Pt(NHNAr)(PEt₃)₂L]⁺, and reduction of the protonated complexes with molecular hydrogen in the presence of a catalyst gives the arylhydrazine complexes trans-[Pt(NH₂NHAr)(PEt₃)₂L]⁺. Some of the spectroscopic properties of these new complexes are reported and discussed.     

On an inconsistency connected with koopman's theorem

On the basis of Koopmans' theorem two methodically different ways to estimate the effect of a spin-orbit perturbation on the ionization potentials of I₂ have been proposed. In the present paper a model system is constructed to show the equivalence of both methods.