Bleomycin A2 (BLMA2, a clinically used drug) and tallysomycin A (TLMA) are two closely related anticancer antibiotics activated by O2 reaction with their Fe(II) complexes. Fe(II) can be modeled by Zn(II). Evidence obtained that the disaccharide and metal-binding domains of ZnTLMA and ZnBLMA2 are superimposable includes the following very similar NMR features:  the 1H and 13C NMR chemical shifts, the 1H and 13C chemical shift changes upon Zn(II) binding, and the NOESY spectra. We evaluated several ZnTLMA structural models with four and five ligating donor atoms from TLMA by using 2D NMR, NOESY back-calculation methods, and restrained molecular mechanics/molecular dynamics calculations. Our results are most consistent with ligation by five N donors, the β-aminoalanine (ALA) amines (NC2 and NC3), the pyrimidinylpropionamide (PRO) pyrimidine (NC10), and the β-hydroxyhistidine amide (NC12) and imidazole (NC29). Metal complexation to TLMA or BLMA2 creates newly stable chiral centers (the metal and the ALA secondary amine, NC3); for the first time, an extensive analysis of the chirality of both centers has been performed. A cross-peak between a PRO H and a disaccharide mannose H is clearly present in the low mixing time NOESY spectrum of ZnTLMA and in the published spectrum of ZnBLMA2. This cross-peak has led us to discover a novel square pyramid (sp) basket arrangement of the drug donor atoms, with PRO NC10 at the apex and SS chirality. A close variant, with donors adopting a trigonal bipyramidal (tbp) arrangement, gave results almost as satisfactory. Our findings raise interesting aspects relevant to drug activation. The literature suggests that the activated form is HO2Fe(III)BLMA2; the five N donors are in an SS-sp I arrangement, with the ALA primary amine (NC2) at the apex. If the Fe(II) form of the drugs had the SS-sp basket or SS-tbp arrangement, addition of O2 could yield products with the drug in an SS-sp I arrangement. Models with RR chirality, such as proposed previously for ZnBLMA2, are energetically unfavorable, cannot account for the NMR results, and cannot readily convert to the SS-sp I geometry. Unlike in RR models, the carbamoyl group of the mannose cannot bind to the metal in SS models. Instead, in our model the disaccharide covers the sixth binding site.

Application of the extended Grunwald-Winstein equation to solvolyses of n-propyl chloroformate in a variety of pure and binary solvents indicates an addition-elimination pathway in the majority of the solvents but an ionization pathway in the solvents of highest ionizing power and lowest nucleophilicity. For methanolysis, a solvent deuterium isotope effect of 2.17 is compatible with the incorporation of general-base catalysis into the substitution process. Activation parameters are consistent with the duality of mechanism. Very modest positive salt effects are observed on adding chloride or bromide salts to the ethanolysis.

A series of mono-or dialkyl/phenyl o-substituted phenoxy ligands in half-metallocene titanium-(IV) complexes was examined to determine the structure-catalytic activity relationship in high temperature olefin polymerization. Five different types of polymerization catalysts with different Cp/Cp* and mono-or disubstituted symmetric/asymmetric alkyl/phenyl phenoxide ancillary ligands were compared. This series was examined for ethylene homopolymerization after activation with Ph 3 CB(C 6 F 5 ) 4 and mMAO-7 at high temperatures (140 °C). Type 4 complexes of compounds 15-18 [33.0-39.0 kg/(mmol of Ti 3 h)] showed much higher catalytic activity than those found in types 1-3 and 5 [3.6-27.6 kg/(mmol of Ti 3 h)], and among the type 4 complexes, the Cp*/2-phenylphenoxy combination of compound 18 [39 kg/(mmol of Ti 3 h)] surpassed the Cp*/2-alkyl ligand systems of compounds 15-17 [33.0-36.0 kg/(mmol of Ti 3 h)]. The revolving nature of the phenoxy ligand around the Ti-O-C axis was identified by the NOSEY correlation peaks between the methyl protons of Cp* and protons of ancillary phenyl phenoxy ligand in compound 18. The conformational flexibility of the phenyl phenoxy ligand was further confirmed by a series of temperature-dependent ROSEY experiments based on the optimization of two conformational structures related by this rotation. Rotational barriers of 4.3 and 6.6 kcal/mol were estimated from theoretical DFT studies. DFT calculations of the transition states for ethylene insertion and termination were carried out for representative examples of types 4 (15, 16, 18), 3 (10, 12), and 1 (3) catalysts as well as the constrained geometry catalyst (CGC) as a reference. The preference for back-side insertion was a unique feature of the monosubstituted type 4 catalysts. The type 4 catalysts showed significant activities for ethylene/1-octene copolymerization affording high molecular weight poly(ethylene-co-1-octene)s (M w = 107 000 -164 000) with unimodal molecular weight distributions (M w /M n = 2.08-4.15). The activity increased in the order of type 3 [90-132 kg/(mmol of Ti 3 h), in toluene, ethylene 30 atm, 1-octene 8 mL, 140 °C, 10 min.] < CGC (222) < type 4 (228-354). Among the type 4 series, compound 18 showed the best performance, reaching an activity of 354 kg/(mmol of Ti 3 h). The polymer density of 0.9148 g/mL for compound 18 was lower than that found in CGC (0.9154 g/mL), indicating higher 1-octene incorporation, which was further confirmed by an analysis of the 13 C NMR spectra of the polymers (18, 2.73 mol % and CGC, 2.55 mol %).

The infrared and Raman spectra of bicyclo[ 1.1 .O] butane and of its 2,3-d2 and 2,2,4,4-d4 isotopomers were redetermined, and the intensities of the infrared bands were measured. A new vibrational assignment was made with the help of the spectrum

Gold(I)‐catalyzed intramolecular 6‐endo‐dig cyclization of tert‐butyl ynoates afforded α‐pyrone cores of violapyrones. Moreover, this reaction was successfully applied to the stereospecific syntheses of (+)‐ and (–)‐violapyrone C, which allowed the absolute configuration of natural (+)‐violapyrone C to be assigned by comparison of the optical rotations. This first total synthesis, which proceeded in 22 % yield over 10 steps from (S)‐(–)‐2‐methylbutanol, features silver(I) oxide promoted monobenzylation of 1,4‐butanediol, Wittig olefination, Claisen condensation, Corey–Fuchs reaction, and gold(I)‐catalyzed α‐pyrone synthesis.