Desaturases fused to their electron donor

Fatty acid desaturations in the carboxy‐terminal segment from C1—C10 are catalyzed in many, but not in all cases, by desaturase enzymes which are fused to their electron donor cytochrome b₅. Several of these enzymes (“front‐end desaturases”) from a wide variety of organisms have been cloned and functionally expressed for proof of regio‐, stereo‐ and chain length‐selectivity. In most cases the actual status of the substrate chain, whether coenzyme A thioester or component of a membrane lipid, is not known. The cytochrome b₅ domain is located N‐terminally, internally or C‐terminally. Compared to the free cytochrome b₅ , the fused domains show a significant reduction of acidic amino acid residues on the surface of the four helices enclosing the heme group. It is discussed how this may contribute to hydrophobic domain pairing required for interdomain electron transport. This is in contrast to the mode of interaction of free cytochrome b₅ with its partners, which is governed by electrostatic charge pairing. A look at crystallized or computer‐simulated models involving fused or free cytochrome b₅ helps to outline the problems encountered by optimizing the docking of partners and the exchange of electrons between domains of different degrees of mobility.     

Electrochemical study of the intermolecular electron transfer to Pseudomonas aeruginosa cytochrome cd1 nitrite reductase

The kinetics of electron transfer reaction between cytochrome cd₁ nitrite reductase (NiR) from Pseudomonas aeruginosa and various physiological/non physiological redox partners was investigated using cyclic voltammetry at the pyrolytic graphite electrode. While NiR did not exchange electron with the electrode, cytochrome c₅₅₁ and azurin, both from Ps. aeruginosa, behaved as fast electrochemical systems. The intermolecular electron transfers between NiR and cytochrome c₅₅₁ or azurin as electron shuttles, in the presence of nitrite, were studied. Second order rate constants of 2×10⁶ and 1.4×10⁵ M⁻¹ s⁻¹ are calculated for cytochrome c₅₅₁ and azurin, respectively. The dependence of the second-order rate constant on ionic strength and pH is discussed. Finally, the effect of the global charge of the electron shuttles was explored using differently charged species (proteins or small ions). The experimental results suggest involvement of polar interactions as well as of hydrophobic contacts in the protein recognition prior to the intermolecular electron transfer. As the cross-reaction between Ps. nautica cytochrome c₅₅₂ and Ps. aeruginosa NiR was shown to be as efficient as the catalytic reaction involving the physiological partners, it is concluded to a ‘pseudo-specificity’ in the recognition between NiR and the electron donor.     

Microsomal enzymes of cholesterol biosynthesis from lanosterol: A progress report

Our principal goal is the complete resolution and reconstitution of the microsomal enzymes of cholesterol biosynthesis. Elucidation of the enzymology has been achieved primarily through dissection of the membrane-bound, 19-step multienzymic process. This report describes the dissection approach through both interruption of specific steps and reconstitution of enzymes that catalyze oxidation of the 14α-methyl group. In earlier work, 4-demethylation was resolved into 3 component reactions catalyzed by: 4-methyl sterol oxidase (NAD[P] H- and O₂-dependnet); steroid 4α-carboxylic acid decarboxylase (NAD-dependent); and 3-ketosteroid reductase (NADPH-dependent). The 3-ketosteroid reductase and decarboxylase have been solubilized with Lubrol WX and deoxycholate, respectively, and characterized. The 4-methyl sterol oxidase (cytochrome b₅-dependent) recently has been solubilized with Renex 690. This study represents successful elucidation of a microsomal enzyme sequence by interruption of the central 10-step segment of the multienzymic formation of cholesterol from lanosterol. The initial C-32 oxidative reaction of 14α-methyl group elimination is catalyzed by a from of cytochrome P-450 that is induced by isosafrole. The induced cytochrome P-450 has been solubilized with Emulgen 913 and purified to homogeneity (17 nmol of cytochrome/mg protein). 24,25-Dihydrolanosterol is oxidized by combination of cytochrome P-450 reductase, hematin, NADPH, glutathione, and the purified, isosafrole-induced cytochrome in an artificial liposome. Oxidation product identification is underway. This study represents successful elucidation of a microsomal multienzymic sequence by solubilization and reconstitution of a segment of the pathway. The remaining enzymes under study are the Δ⁸→Δ⁷ isomerase and 3 NADPH-dependent double bond reductases that catalyze reduction of: Δ⁷, Δ¹⁴- Δ²⁴-sterol double bonds. Purification of these nonoxygenrequiring enzymes is in progress. Resolution of the enzymes has demonstrated unequivocally that cholesterol synthesis via this pathway could not have appeared biologically until membranes containedboth the cytochrome P-450- and cytochrome b₅-electron transport enzymes. Chemically, all enzymic attacks in the formation of cholesterol from lanosterol appear to be initiated on the α-face of the relatively planar steroids. Thus, considerable genetic pressure must have been needed for the stereospecific clearing of the steroidal α-face to form the mature membrane component, cholesterol.     

CYP51: A Major Drug Target in the Cytochrome P450 Superfamily

The cytochrome P540 (CYP) superfamily currently includes about 9000 proteins forming more than 800 families. The enzymes catalyze monooxygenation of a vast array of compounds and play essentially two roles. They provide biodefense (detoxification of xenobiotics, antibiotic production) and participate in biosynthesis of important endogenous molecules, particularly steroids. Based on these two roles, sterol 14/*alpha*/-demethylases (CYP51) belong to the second group of P450s. The CYP51 family, however, is very special as its members preserve strict functional conservation in enzyme activity in all biological kingdoms. At amino acid identity across the kingdoms as low as 25-30%, they all catalyze essentially the same three-step reaction of oxidative removal of the 14/*alpha*/-methyl group from the lanostane frame. This reaction is the required step in sterol biosynthesis of pathogenic microbes. We have shown that specific inhibition of protozoan CYP51 can potentially provide treatment for human trypanosomiases. Three sets of CYP51 inhibitors tested in vitro and in trypanosomal cells in this study include azoles [best results being 50% cell growth inhibition at <1 and at 1.3 muM for Trypanosoma cruzi (TC) and Trypanosoma brucei (TB), respectively], non-azole compounds (50% TC cell growth inhibition at 5 microM) and substrate analogs of the 14/*alpha*/-demethylase reaction. 32-Methylene cyclopropyl lanost-7-enol exhibited selectivity toward TC with 50% cell growth inhibition at 3 microM.     

Molecular Genetics of Plant Sterol Backbone Synthesis

Sterols, which are biosynthesized via the cytoplasmic mevalonate (MVA) pathway, are important structural components of the plasma membrane and precursors of steroid hormones in both vertebrates and plants. Ergosterol and cholesterol are the major sterols in yeast and vertebrates, respectively. In contrast, plants produce a wide variety of phytosterols, which have various functions in plant development. Although the general biosynthetic pathway to plant sterols has been defined, the details of the biochemical, physiological, and developmental functions of genes involved in the biosynthetic network and their regulation are not well understood. Molecular genetic analyses are an effective approach to use when studying these fascinating problems. Since three enzymes, 3-hydroxy-3-methylglutaryl CoA reductase, farnesyl diphosphate synthase, and lanosterol synthase, have been functionally characterized in planta, we reviewed recent progress on these enzymes. Arabidopsis T-DNA and transposon insertion mutants are now widely available. The use of molecular genetics, molecular biology, and bioorganic chemical approaches on these mutants, as well as inhibitors of the MVA pathway, should help us to understand plant sterol biosynthesis comprehensively.     

Electron Donation in Photosystem II

The pathways of electron donation in Photosystem II (PS II) as studied by electron paramagnetic resonance (EPR) and time-resolved optical spectroscopy are discussed. The EPR studies have defined two competing pathways of electron donation in PS II, from cytochrome b₅₅₉ and from the Mn site of the oxygen-evolving center. The kinetics of re-reduction of the primary electron donor of PS II (P₆₈₀). as measured by optical spectroscopy, are re-evaluated in light of the EPR results. We propose that the 35-μs kinetic component is due to the reduction of chlorophyll, an alternate electron donor on the cytochrome b₅₅₉ pathway, rather than to the reduction of P₆₈₀. The chlorophyll/cytochrome b₅₅₉ pathway has been proposed to be part of a cyclic electron transfer pathway around PS II; we suggest that photooxidation of chlorophyll is the first step leading to photoinhibition and that cytochrome b₅₅₉ serves to protect PS II from photoinhibition by rapidly re-reducing the oxidized chlorophyll (Thompson, L.K.; Brudvig, G.W. Biochemistry, 1988, 27 : 6653). These results and proposals are summarized in an overall scheme of electron transfer pathways and rates in PS II.     

A Caged,Destabilized, Free Radical Intermediate in the Q‐Cycle

The Rieske/cytochrome b complexes, also known as cytochrome bc complexes, catalyze a unique oxidant‐induced reduction reaction at their quinol oxidase (Q_o) sites, in which substrate hydroquinone reduces two distinct electron transfer chains, one through a series of high‐potential electron carriers, the second through low‐potential cytochrome b. This reaction is a critical step in energy storage by the Q‐cycle. The semiquinone intermediate in this reaction can reduce O₂ to produce deleterious superoxide. It is yet unknown how the enzyme controls this reaction, though numerous models have been proposed. In previous work, we trapped a Q‐cycle semiquinone anion intermediate, termed SQ_o, in bacterial cytochrome bc₁ by rapid freeze‐quenching. In this work, we apply pulsed‐EPR techniques to determine the location and properties of SQ_o in the mitochondrial complex. In contrast to semiquinone intermediates in other enzymes, SQ_o is not thermodynamically stabilized, and can even be destabilized with respect to solution. It is trapped in Q_o at a site that is distinct from previously described inhibitor‐binding sites, yet sufficiently close to cytochrome b_L to allow rapid electron transfer. The binding site and EPR analyses show that SQ_o is not stabilized by hydrogen bonds to proteins. The formation of SQ_o involves “stripping” of both substrate ‐OH protons during the initial oxidation step, as well as conformational changes of the semiquinone and Q_o proteins. The resulting charged radical is kinetically trapped, rather than thermodynamically stabilized (as in most enzymatic semiquinone species), conserving redox energy to drive electron transfer to cytochrome b_L while minimizing certain Q‐cycle bypass reactions, including oxidation of prereduced cytochrome b and reduction of O₂.     

Elaboration of Poly(ε‐caprolactone)‐g‐TiNbO5 Nanocomposites via in situ Metal Complex Initiated Intercalative Polymerization

Summary: The preparation of poly(ε‐caprolactone)‐g‐TiNbO₅ nanocomposites via in situ intercalative polymerization of ε‐caprolactone initiated by an aluminium complex is described. These nanocomposites were obtained in the presence of HTiNbO₅ mineral pre‐treated by AlMe₃, but non‐modified by tetraalkylammonium cations. These hybrid materials obtained have been characterized by Fourier transform infrared absorption spectroscopy, wide‐angle X‐ray scattering, scanning electron microscopy, and dynamic mechanical analysis. Layered structure delamination and homogeneous distribution of mineral lamellae in the poly(ε‐caprolactone) (PCL) is figured out and strong improvement of the mechanical properties achieved. The storage modulus of the nanocomposites is enhanced as compared to pure PCL and increases monotonously with the amount of the filler in the range 3 to 10 wt.‐%.

SEM image of the fractured surface of a PCL‐TiNbO₅ nanocomposite film.     

Olefin production by cofeeding methanol and n‐butane: Kinetic modeling considering the deactivation of HZSM‐5 zeolite

The joint transformation of methanol and n‐butane fed into a fixed‐bed reactor on a HZSM‐5 zeolite catalyst has been studied under energy neutral conditions (methanol/n‐butane molar ratio of 3/1). The kinetic scheme of lumps proposed integrates the reaction steps corresponding to the individual reactions (cracking of n‐butane and MTO process at high‐temperature) and takes into account the synergies between the steps of both reactions. The deactivation by coke deposition has been quantified by an expression dependent on the concentration of the components in the reaction medium, which is evidence that oxygenates are the main coke precursors. The concentration of the components in the reaction medium (methanol, dimethyl ether, n‐butane, C₂? C₄ paraffins, C₂? C₄ olefins, C₅? C₁₀ lump, and methane) is satisfactorily calculated in a wide range of conditions (between 400 and 550°C, up to 9.5 (g of catalyst) h (mol CH₂)^?1 and with a time on stream of 5 h) by combining the equation of deactivation with the kinetic model of the main integrated process. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Pristanic acid is activator of peroxisome proliferator activated receptor alpha

lsoprenoid phytanic acid (3,7,11,15‐tetramethylhexadecanoic acid) is degraded in peroxisomes by α‐oxidation to pristanic acid (2,6,10,14‐tetramethylpentadecanoic acid) and then via β‐oxidation. Branched‐chain phytanic acid is an activator of the peroxisome proliferator activated receptor α (PPAR ) which in liver cells regulates expression of genes encoding peroxisomal and mitochondrial β‐oxidative enzymes as well as cytosolic/nuclear liver‐type fatty acid binding protein (L‐FABP). In this report we address the question whether pristanic acid also acts as activator of PPARα and thus mediates the expression of its catabolizing enzymes. In a first in vivo approach we fed pristanic acid for 14 days to wildtype mice and to mice lacking sterol carrier protein 2/sterol carrier protein x which Ieads to a phenotype having high concentrations of branched‐chain fatty acids. In either genotype, feeding pristanic acid was associated with a strong induction of peroxisomal β‐oxidation enzymes tested (acyl‐CoA oxidase, bifunctional enzyme, thiolase) as well as of L‐FABP. The link between pristanic acid and protein expression observed was established by carrying out assays for transactivation of PPARα in transfected HepG2 cells. In comparison to hypolipidemic drugs and to straight‐chain fatty acids known to be PPARα agonists, branched‐chain phytanic and pristanic acids were substantially stronger activators, pristanic acid being even superior to phytanic acid.     

Design and synthesis of thieno[3,4‐c]pyrrole‐4,6‐dione based conjugated copolymers for organic solar cells

A new series of conjugated copolymers (PBDT‐TPD , PBDT ‐Th‐TPD , PBDT‐TT‐TPD ) containing donor–acceptor (D ? A) structure electron‐rich benzo[1,2‐b :4,5‐b ′]dithiophene (BDT ) units with branched alkyl thiophene side chains and electron‐deficient 5‐(2‐octyl)‐4H ‐thieno[3,4‐c ]pyrrole‐4,6(5H )‐dione (TPD) units was designed and synthesized. To tune the optical and electrochemical properties of the copolymers, the conjugation length of the copolymers was extended by introducing π‐conjugated spacers such as thiophene and thieno[3,2‐b ]thiophene units. It was observed that PBDT‐TPD showed broader absorption spectra in the longer wavelength region and the absorption maximum was red‐shifted compared to that of PBDT‐Th‐TPD, PBDT‐TT‐TPD. Stokes shifts were calculated to be 52 nm for PBDT‐TPD, 153 nm for PBDT‐Th‐TPD and 146 nm for PBDT‐TT‐TPD. Further, PBDT‐TPD exhibited a deeper highest occupied molecular orbital energy level of ?5.53 eV as calculated by cyclic voltammetry. Bulk heterojunction solar cells fabricated using PBDT‐TPD as donor material exhibited a power conversion efficiency of 1.92%. © 2017 Society of Chemical Industry     

Tailor‐Made Designer Helical Peptides that Induce Mitochondrion‐Mediated Cell Death without Necrosis

Managing protein–protein interactions is essential for resolving unknown biological events at the molecular level and developing drugs. We have designed and synthesized a side‐chain‐crosslinked helical peptides based on the binding domain of a pro‐apoptotic protein (Bad) that induces programed cell death. The peptide showed high helical content and bound to its target, Bcl‐X_L, more strongly than its non‐crosslinked counterparts. When HeLa cells were incubated with the crosslinked peptide, the peptide entered the cytosol across the plasma membrane. The peptide formed a stable complex with Bcl‐X_L localized at the outer mitochondrial membrane, and this binding event caused the release of cytochrome c from the intermembrane space of mitochondria into the cytosol. This activated the caspase cascade: 70 % of HeLa cells died by the apoptosis pathway (without evidence of necrosis).     

Interface properties of cytochrome c on a nano-textured diamond surface

The electron transfer process and the peroxidase activity of native and denatured cytochrome c were investigated on OH-terminated diamond nano-textured surfaces. The nano-textured surfaces with geometrical properties of typical protein dimensions were fabricated by a top-down technology, where diamond nanoparticles are used as etching masks. The cyclic voltammogram of native cytochrome c shows an adsorption-controlled, reversible electron transfer process of the heme redox center, which was not detected for denatured cytochrome c. Native cytochrome c denatures in the presence of hydrogen peroxide. Higher peroxidase activity was found on the denatured cytochrome c than on native cytochrome c. The apparent Michaelis-Menten constants K_m for denatured cytochrome c and the native cytochrome c were determined to be 0.08 and 0.23 mM, respectively.     

4-Methylzymosterone and Other Intermediates of Sterol Biosynthesis from Yeast Mutants Engineered in the ERG27 Gene Encoding 3-Ketosteroid Reductase

Studies in the post‐squalene section of sterol biosynthesis may be hampered by the poor availability of authentic standards. The present study used different yeast strains engineered in 3‐ketosteroid reductase (Erg27p) to obtain radioactive and non‐radioactive intermediates of sterol biosynthesis hardly or not available commercially. Non‐radioactive 3‐keto 4‐monomethyl sterones were purified from non‐saponifiable lipids extracted from cells bearing point‐mutated 3‐ketosteroid reductase. Two strategies were adopted to prepare the radioactive compounds: (1) incubation of cell homogenates of an ERG27‐deletant strain with radioactive lanosterol, (2) incubation of growing cells of a strain expressing point‐mutated 3‐ketosteroid reductase with radioactive acetate. Chemical reduction of both radioactive and non‐radioactive 3‐keto sterones gave the physiological 3‐β OH sterols, as well as the non‐physiological 3‐α OH isomers. This combined biological and chemical preparation procedure provided otherwise unavailable or hardly available 4‐mono‐methyl intermediates of sterol biosynthesis, paving the way for research into their roles in physiological and pathological conditions.     

Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors

11β‐Hydroxysteroid dehydrogenases (11β‐HSDs) are key enzymes regulating the pre‐receptor metabolism of glucocorticoid hormones. The modulation of 11β‐HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue‐specific glucocorticoid action by regulating 11β‐HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11β‐HSD1. The most active compounds identified ( 52 , 62 , 72 , 92 , 103 and 104 ) display potent inhibition of 11β‐HSD1 with IC₅₀ values in the 50–70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X‐ray crystal structures of human 11β‐HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.     

Liposome Microencapsulation for the Surface Modification and Improved Entrapment of Cytochrome c for Targeted Delivery

In this study, we established a procedure based on the microencapsulation vesicle (MCV) method for preparing surface‐modified liposomes, using polyethylene glycol (PEG) and a site‐directed ligand, with high entrapment efficiency of cytochrome c (Cyt c). For preparing a water‐in‐oil (W/O) emulsion, egg phosphatidylcholine and cholesterol were dissolved in organic solvents (O phase) and emulsified by sonication with aqueous solution of Cyt c (W₁). Although the dispersion stability of the W₁/O emulsion was low when n‐hexane was used to dissolve the lipids in the O phase, it was substantially improved by using mixed solvents consisting of n‐hexane and other organic solvents, such as ethanol and dichloromethane (DCM). The W₁/O emulsion was then added to another water phase (W₂) to prepare the W₁/O/W₂ emulsion. PEG‐ and/or ligand‐modified lipids were introduced into the W₂ phase as external emulsifiers not only for stabilizing the W₁/O/W₂ emulsion but also for modifying the surface of liposomes obtained later. After solvent evaporation and extrusion for downsizing the liposomes, approximately 50% of Cyt c was encapsulated in the liposomes when the mixed solvent consisting of n‐hexane and DCM at a volume ratio of 75/25 was used in the O phase. Finally, the fluorescence‐labeled liposomes, with a peptide ligand having affinity to the vasculature in adipose tissue, were prepared by the MCV method and intravenously injected into mice. Confocal microscopy showed the substantial accumulation of these liposomes in the adipose tissue vessels. Taken together, the MCV technique, along with solvent optimization, could be useful for generating surface‐modified liposomes with high drug entrapment efficiency for targeted delivery.     

Differentiation of Mechanically and Chemically Extracted Hazelnut Oils Based on their Sterol and Wax Profiles

The sterol and wax content of solvent extracted (SEHO) and cold pressed hazelnut oils (CPHO) were compared. A total of 48 samples from 19 hazelnut varieties were collected for two successive crop years from four different geographical districts in Turkey. Hazelnuts were processed to oil with a laboratory scale press, than the remaining oil in cake was extracted with n‐hexane. CPHO and SEHO were evaluated for their wax, sterol and squalene contents. Results showed that sterol, squalene and wax contents of all individual cultivars were higher in SEHO than those of CPHO, indicating the higher solubility of these compounds in solvent. Total sterol contents ranged between 1088.56 (Kargalak)—1609.39 mg/kg (Mincane) for CPHO and 1590.86 (Çak?ldak)—2897.26 mg/kg (Mincane) for SEHO. Hazelnut oils were found to be richer of C36‐38 esters than C40‐46 group. Total wax content was between 24.19 (Kargalak)—94.58 mg/kg (Ku?) for CPHO and 81.46 (Kargalak)—160.92 mg/kg (Akçakoca) for SEHO. The squalene amounts of the samples obtained by hexane extraction were between 499.75 (Allahverdi)—885.36 mg/kg (Cavcava), while it varied between 288.55 (Kargalak)—647.68 mg/kg (Mincane) in cold pressed oils. Significant and obvious variations between SEHO and CPHO were verified by principal component and hierarchical cluster analysis. Geographical discrimination was also achieved by discriminant analysis.     

Effects of Variety,Maturation and Growing Region on Chemical Properties,Fatty Acid and Sterol Compositions of Virgin Olive Oils

Chemical properties, fatty acid and sterol compositions of olive oils extracted from Gemlik and Halhal? varieties grown in Hatay and Mardin provinces in Turkey were investigated during four maturation stages. The olive oil samples were analyzed for their chemical properties such as free acidity, peroxide value, total carotenoid, total chlorophyll, total phenolic contents, antioxidant activity, fatty acid and sterol compositions. Chemical properties, fatty acids and sterol profiles of olive oil samples generally showed statistically significant differences depending on the varieties, maturation and growing areas (p < 0.05). As free fatty acid contents and total phenolic contents increased, total carotenoid and chlorophyll contents decreased throughout the maturity stages. Total carotenoid and chlorophyll contents of oil samples from Mardin were higher than those of Hatay. The total phenolic compounds of olive oil samples ranged from 20.62 in Gemlik to 525.22 mg GAE/kg oil in Halhal? from Hatay. In general, the phenolic contents and antioxidant activities of olive oil samples were positively associated. Oleic acid content was the highest 71.53 % in H1 samples in Hatay. Total sterol contents were 1194.33 mg/kg in Halhal? and 2008.66 mg/kg in Gemlik from Hatay. Stigmasterol contents of oils obtained from Hatay were lower than those of Mardin. Oleic acid, palmitic acid, β‐sitosterol, ?‐5‐avenasterol and campesterol contents fluctuated with maturation for each of variety from both growing regions. These results showed that the variety, growing area and maturation influence the chemical properties, fatty acid and sterol compositions.     

A single active site metal center of neodymocene chloride for the ring‐opening polymerization of ε‐caprolactone

A germyl‐bridged lanthanocene chloride, Me₂Ge(^tBu‐C₅H₃)₂LnCl (Ln = Nd; (Cat‐ Nd ), was prepared and successfully used as single catalyst to initiate the ring‐opening polymerization of ε‐caprolactone (ε‐CL) for the first time. Under mild conditions (60°C,[ε‐CL]/[Ln] = 200, 4 h), Cat‐ Nd efficiently catalyzes the polymerization of ε‐CL, giving poly(ε‐caprolactone) (PCL) with high molecular weight (MW) (>2.5 × 10⁴) in high yield (>95%). The effects of molar ratio of [ε‐CL]/Cat‐Nd, polymerization temperature and time, as well as solvent were determined in detail. When the polymerization is carried out in bulk or in petroleum ether, it gives PCL with higher MW and perfect conversion (100%). The higher catalytic activity of this neodymocene chloride could be ascribed to the bigger atom in the bridge of bridged ring ligands. Some activators, such as NaBPh₄, KBH₄, AlEt_3, and Al(i‐Bu)₃, can promote the polymerization of ε‐CL by Cat‐ Nd, which leads to an increase both in the polymerization conversion and in the MW of PCL. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123: 1212–1217, 2012