Further crystallographic evidence of NH· · ·π (system) and CO· · ·π (system) interactions: The structures of bis(diarylhydrazonecarbonyl)methylene derivatives [{ArPhCNNH—C(O)}2CH2] (Ar = Ph, 2‐C5H4N, 2‐C4H3S)

In this study are reported the syntheses of three bis(diarylhydrazonecarbonyl)methylene derivatives [{ArPhCNNH C(O)}₂CH₂] [Ar = 2 C₅H₄N (5), C₆H₅ (6), and 2‐C₄H₃S (7)], obtained by condensation of corresponding hydrazones with carbon suboxide, C₃O₂. The solid‐state self‐assembly of these carbonyl derivatives, giving rise to polymeric and dimeric networks, is described. In the formation of these structural features, in addition to N—H· · ·OC intermolecular hydrogen bonds, stabilizing intramolecular NH· · · π (systems) and intermolecular CO· · ·π (systems) interactions also seem to play an important role. Solution ¹H‐nmr data of compounds 5–7 indicate that the polymeric and dimeric structures are not maintained in solution and show the occurrence of keto‐enolic equilibria. © 1999 John Wiley & Sons, Inc. Biopoly 49: 541–549, 1999     

ω‐Turn: A novel β‐turn mimic in globular proteins stabilized by main‐chain to side‐chain CH···O interaction

Mimicry of structural motifs is a common feature in proteins. The 10‐membered hydrogen‐bonded ring involving the main‐chain C?O in a β‐turn can be formed using a side‐chain carbonyl group leading to Asx‐turn. We show that the N? H component of hydrogen bond can be replaced by a C^γ‐H group in the side chain, culminating in a nonconventional C? H···O interaction. Because of its shape this β‐turn mimic is designated as ω‐turn, which is found to occur ～three times per 100 residues. Three residues (i to i + 2) constitute the turn with the C? H···O interaction occurring between the terminal residues, constraining the torsion angles ?_{i + 1}, ψ_{i + 1}, ?_{i + 2} and χ′_{1(i + 2)} (using the interacting C^γ atom). Based on these angles there are two types of ω‐turns, each of which can be further divided into two groups. C^β‐branched side‐chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. With Cys occupying the i + 1 position, such turns are found in the metal‐binding sites. N‐linked glycosylation occurs at the consensus pattern Asn‐Xaa‐Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω‐turn, which may be the recognition site for protein modification. Location between two β‐strands is the most common occurrence in protein tertiary structure, and being generally exposed ω‐turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design. Proteins 2015; 83:203–214. © 2014 Wiley Periodicals, Inc.     

Synthesis by Ring‐Closing Alkyne Metathesis with Selective Hydrogenation,and Olfactory Comparison of (7E)‐ and (7Z)‐Cyclohexadec‐7‐enone (Aurelione®)

Both C?C‐bond isomers of cyclohexadec‐7‐enone ( 6 , Aurelione^®) were selectively synthesized via cyclohexadec‐7‐ynol ( 16 ) by ring‐closing alkyne metathesis of icosa‐2,18‐diyn‐9‐ol ( 15 ), employing an in situ‐formed catalyst from Mo(CO)₆ and 4‐(trifluoromethyl)phenol. Pyridinium chlorochromate (PCC) oxidation and subsequent Lindlar hydrogenation afforded the (7Z)‐configured isomer (7Z)‐ 6 , while hydrosilylation of the intermediate cyclohexadec‐7‐ynone ( 17 ), followed by desilylation, provided the (7E)‐configured cyclohexadec‐7‐enone ((7E)‐ 6 ). The substrate for the alkyne metathesis was prepared from cycloheptanone ( 7 ) by cycloaddition of chloromethylcarbene to its trimethylsilyl enol ether 8 , and subsequent ring enlargement of the adduct 9 under rearrangement to 2‐methylcyclooct‐2‐enone ( 10 ), which was subjected to Weitz? Scheffer epoxidation and Eschenmoser? Ohloff fragmentation to non‐7‐ynal ( 12 ). Its reaction with the Grignard reagent of 11‐bromoundec‐2‐yne ( 14 ), prepared from the corresponding alcohol 13 by Appel? Lee bromination, furnished the icosa‐2,18‐diyn‐9‐ol ( 15 ). While both isomers of cyclohexadec‐7‐enone ( 6 ) possess warm and powdery musk odors with tobacco‐type ambery accents, (7Z)‐ 6 is more animalic and waxy, whereas (7E)‐ 6 was found to be more floral, sweet, and hay‐like in tonality. Interestingly, however, with odor detection thresholds of 2.0 ng/l air and 2.3 ng/l air, respectively, both (7Z)‐ 6 and (7E)‐ 6 were found to be almost identical in their odor strength, with the (7Z)‐ 6 being only very slightly more powerful.     

Lone pair ··· π interactions between water oxygens and aromatic residues: Quantum chemical studies based on high‐resolution protein structures and model compounds

The π electron cloud of aromatic centers is known to be involved in several noncovalent interactions such as C—H···π, O—H···π, and π···π interactions in biomolecules. Lone-pair (lp) ··· π interactions have gained attention recently and their role in biomolecular structures is being recognized. In this article, we have carried out systematic analysis of high-resolution protein structures and identified more than 400 examples in which water oxygen atoms are in close contact (distance < 3.5 Å) with the aromatic centers of aromatic residues. Three different methods were used to build hydrogen atoms and we used a consensus approach to find out potential candidates for lp···π interactions between water oxygen and aromatic residues. Quantum mechanical calculations at MP2/6-311++G(d,p) level on model systems based on protein structures indicate that majority of the identified examples have energetically favorable interactions. The influence of water hydrogen atoms was investigated by sampling water orientations as a function of two parameters: distance from the aromatic center and the angle between the aromatic plane and the plane formed by the three water atoms. Intermolecular potential surfaces were constructed using six model compounds representing the four aromatic amino acids and 510 different water orientations for each model compound. Ab initio molecular orbital calculations at MP2/6-311++G(d,p) level show that the interaction energy is favorable even when hydrogen atoms are farthest from the aromatic plane while water oxygen is pointing toward the aromatic center. The strength of such interaction depends upon the distance of water hydrogen atoms from the aromatic substituents. Our calculations clearly show that the lp···π interactions due to the close approach of water oxygen and aromatic center are influenced by the positions of water hydrogen atoms and the aromatic substituents.     

A Comparative Study of In Vitro Cytotoxic,Antioxidant, and Antimicrobial Activity of Pt(II), Zn(II), Cu(II), and Co(III) Complexes with N‐heteroaromatic Schiff Base (E)‐2‐[N′‐(1‐pyridin‐2‐yl‐ethylidene)hydrazino]acetate

In search for novel biologically active metal based compounds, an evaluation of in vitro cytotoxic, antioxidant, and antimicrobial activity of new Pt(II) complex and its Zn(II), Cu(II), and Co(III) analogues, with NNO tridentately coordinated N‐heteroaromatic Schiff base ligand (E)‐2‐[N′‐(1‐pyridin‐2‐yl‐ethylidene)hydrazino]acetate, was performed. Investigation of antioxidative properties showed that all of the compounds have strong radical scavenging potencies. The Zn(II) complex showed potent inhibition of DNA cleavage by hydroxyl radical. A cytotoxic action of investigated compounds was evaluated on cultures of human promyelocitic leukaemia (HL‐60), human glioma (U251), rat glioma (C6), and mouse melanoma (B16) cell lines. It was shown that binuclear pentacoordinated Zn(II) complex possesses a strong dose‐dependent cytotoxic activity, of the same order of magnitude as cisplatin on B16, C6, and U251 cells. Furthermore, Zn(II) complex causes oxidative stress‐induced apoptotic death of HL‐60 leukemic cells, associated with caspase activation, phosphatidylserine externalization, and DNA fragmentation.     

Lipase‐Catalyzed Kinetic Resolution of (±)‐1‐(2‐Furyl) Ethanol in Nonaqueous Media

S‐1‐(2‐Furyl) ethanol serves as an important chiral building block for the preparation of various natural products, fine chemicals, and is widely used in the chemical and pharmaceutical industries. In this work, lipase‐catalyzed kinetic resolution of (R/S)‐1‐(2‐furyl) ethanol using different acyl donors was investigated. Vinyl esters are good acyl donors vis‐à‐vis alkyl esters for kinetic resolution. Among them, vinyl acetate was found to be the best acyl donor. Different immobilized lipases such as Rhizomucor miehei lipase, Thermomyces lanuginosus lipase, and Candida antarctica lipase B were evaluated for this reaction, among which C. antarctica lipase B, immobilized on acrylic resin (Novozym 435), was found to be the best catalyst in n‐heptane as solvent. The effect of various parameters was studied in a systematic manner. Maximum conversion of 47% and enantiomeric excess of the substrate (ee_s) of 89% were obtained in 2 h using 5 mg of enzyme loading with an equimolar ratio of alcohol to vinyl acetate at 60°C at a speed of 300 rpm in a batch reactor. From the analysis of progress curve and initial rate data, it was concluded that the reaction followed the ordered bi–bi mechanism with dead‐end ester inhibition. Kinetic parameters were obtained by using nonlinear regression. This process is more economical, green, and easily scalable than the chemical processes. Chirality 26:286–292, 2014. © 2014 Wiley Periodicals, Inc.