bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure assignment of some 3,4′‐diquinolinyl sulfides studied by Nuclear Overhauser Effects, X‐ray analysis and reactions with sodium methoxide
Authors: Boryczka Stanislaw , Maślankiewicz Andrzej , Wyszomirski Miroslaw , Borowiak Teresa , Kubicki Maciej 
Published: September 2010

Abstract1H NMR spectral assignment and nuclear Overhauser enhancement studies of 3‐[[3‐(methylthio)‐4‐quinolinyl]thio]‐4‐methoxyquinoline (2) and ‐4(1H)‐quinolinone (3) were carried out. The structure of compound 2a (R = R′ = Me) was also confirmed by X‐ray analysis. Reactions of compounds of types 2 and 3 with sodium methoxide proceeded with the cleavage of 4‐quinolinyl‐sulfur bond yielding two molecules of 3‐(methylthio)quinolines of type 4 or types 4 and 5.
Towards a rational design of resolving agents. Part III. structural study of two pairs of diastereomeric salts of ephedrine and a cyclic phosphoric acid
Authors: Leusen F. J. J. , Slot H. J. Bruins , Noordik J. H. , van der Haest A. D. , Wynberg H. , Bruggink A. 
Published: September 2010

AbstractThe crystal structures of two pairs of diastereomeric salts consisting of ephedrine and a cyclic phosphoric acid were analyzed in detail. One pair (R = H; Figure 1) shows no difference in solubility, as reflected in identical non‐bonded interaction patterns in the two salts. The other pair (R = CI; Figure 1) shows a significant solubility difference; the crystal packings of these two salts differ considerably. The less soluble salt shows far more favorable Van der Waals interactions, presenting further evidence that the result of optical resolutions by selective crystallization are determined by these weak interactions. This study, in combination with the results presented in the previous paper (Towards a rational design of resolving agents, Part II), suggests that a model might be developed describing a (quantitative) relationship between the lattice energy difference in a diastereomeric pair and the resolution efficiency of the resolving agent.
CO2 hydrogenation into methanol on supported nickel‐molybdenum catalysts
Authors: Ghazi M. , Barrault J. , Menezo J. C. 
Published: September 2010

AbstractActivity and selectivity in carbon dioxide hydrogenation reactions depend on the nature of the catalyst support. On alumina, methane is the major reaction product whereas on zinc oxide methanol is formed preferably, however with formation of much carbon monoxide.Kinetic and FTIR measurements show that methanol formation is favored on a ZnO support and reinforce the hypothesis of a direct transformation of carbon dioxide to methanol.
Transimination. Conversion of nitriles into secondary amines in a one‐pot reaction
Authors: Brussee J. , van der Gen A. 
Published: September 2010

AbstractTransimination has been used as a key step in a convenient, highly erythro selective, one‐pot synthesis of N‐substituted β‐ethanolamines from (R)‐(+)‐[(tert‐butyldimethylsilyl)oxy]‐benzeneacetonitrile (OTBS‐mandelonitrile).
Oxidative methylation of (η5‐C5 Me5)2 TiX (X = Cl, OMe, Me) with group 12 dimethyl complexes to diamagnetic (η5‐C5Me5)2TiX(Me)
Authors: Luinstra Gerrit A. , Teuben Jan H. 
Published: September 2010

AbstractTervalent titanium compounds (C5Me5)2TiX (X = OMe, Cl, Me) are selectively oxidized and alkylated at room temperature by ZnMe2 to diamagnetic monomethyl derivatives (C5Me5)2TiX(Me).
Enzymatic optical resolution of norbornanecarboxylic esters using pig liver esterase
Authors: van Gael F. J. C. , Klunder A. J. H. , Zwanenburg B. 
Published: September 2010

AbstractThe hydrolysis of a series of norbornane‐type carboxylic esters catalyzed by pig liver esterase (PLE) has been investigated. It was found that an exo‐eer function (syn to the C7 methylene group) is hydrolyzed with high preference. Enantioselective hydrolysis can be accomplished when a vicinal carbonyl‐containing function (eer, formyl, acetyl) is present in a trans position with respect to the exo eer. The regiospecificity of the enzymatic hydrolysis has been used for the separation of exo/endo mixtures of the cycloadducts derived from cyclopentadiene and alkene esters. The regiospecificity and enantioselectivity of the enzymatic hydrolysis of norbornane‐type esters were analyzed in terms of Tamm's substrate model and also by Griengl's method.
Hydroxynitrile lyases from almond and sorghum as biocatalysts
Authors: Smitskamp‐Wilms E. , Brussee J. , van der Gen A. , van Scharrenburg G. J. M. , Sloothaak J. B. 
Published: September 2010

AbstractHydroxynitrile lyases from sweet almond (E.C. 4.1.2.10) and from sorghum bicolor (E.C. 4.1.2.11) have been purified to homogeneity by ion‐exchange chromatography. These enzymes catalyse the decomposition of α‐hydroxynitriles to aldehydes and hydrocyanic acid (HCN) and show great promise for synthetic applications in the reverse reaction: the stereospecific addition of HCN to aldehydes to form enantio‐pure α‐hydroxynitriles.Physical and kinetic characteristics of the two dominating isoenzymes in each source were compared and revealed appreciable species‐specific differences. The differences in substrate specificity between iso forms within one species, were, however, found to be small.The native molecular weight for the sorghum lyase was found to be 95 kDa. This is in contrast with an earlier reported value of 180 kDa. From the kinetic parameters Km and Kmax, a specificity constant was calculated, which can be used to predict the potential application of oxynitrilase as a biocatalyst for specific synthetic purposes.
Biosynthesis and chemical determination of polyfluoro‐4‐hydroxyanilines
Authors: Rietjens I. M. C. M. , Koerts J. , Boeren S. , Vervoort J. 
Published: September 2010

AbstractThis paper describes methods for the biosynthesis and chemical determination of polyfluorinated 4‐hydroxyanilines.19F NMR was routinely used to determine recoveries and metabolite patterns.Male Wistar rats exposed toortho‐ and/ormeta‐polyfluorinated anilines were shown, by19F NMR analysis of urine samples, to excrete a large percentage of the administered dose as the corresponding 4‐aminophenyl sulphate. Using a Bio‐Gel P2 column, this metabolite could be separated from the other metabolites and from (nearly) all urine contaminants. Treatment of the pooled fractions of the Bio‐Gel P2 column with arylsulphatase resulted in hydrolysis of the 4‐aminophenyl sulphate, giving rise to the corresponding polyfluoro‐4‐hydroxyaniline.The yields of this biosynthetic pathway varied between 10 and 65% depending on the substitution pattern. The yield is mainly determined by the extent to which thein‐vivobiotransformation results in the desired 4‐aminophenyl sulphate and its separation from other urine metabolites on the Bio‐Gel P2 column.The amounts of polyfluoro‐4‐hydroxyanilines prepared in this way were sufficient to develop a chemical assay for their determination and quantification in biological samples in the μM range. It was demonstrated that polyfluoro‐4‐hydroxyanilines can be measured using the assay described for nonfluorinated 4‐hydroxyaniline.
Optimization of alcohol dehydrogenase activity and NAD(H) regeneration in organic solvents
Authors: Snijder‐Lambers A. M. , Vulfson E. N. , Doddema H. J. 
Published: September 2010

AbstractAlcohol dehydrogenase (EC 1.1.1.1.) and NAD were co‐immobilized on different supports and used as biocatalysts in organic solvents. Both horse liver alcohol dehydrogenase and yeast alcohol dehydrogenase were tested as biocatalysts for the oxidation of primary alcohols or the reduction of aldehydes. The influence of the kind of support, solvent, water content of the reaction mixture and kind and concentration of the substrates on the redox reaction rate was investigated. NAD(H) was regenerated with the aid of a second substrate. It was shown that both alcohols and aldehydes can serve as reaction media for biocatalysis at molar concentrations, provided the solvents are saturated with water. Highest enzyme activity (2 IU · mg−1 for horse liver alcohol dehydrogenase) was obtained when a hydrophobic long‐chain aldehyde or pentanol was used as the second substrate. Using high concentrations of the second substrate, an equilibrium shift towards over 95 % conversion of substrate was obtained. High total turnover numbers for NAD and NADH of about one million were realized. Thus, coenzyme costs were reduced to about 0.01 US$ per kilogramme of product. This means that the enzyme cos (bout 1000 US$ per kilogramme of product) have become the limiting factor for the application of both alcohol dehydrogenases in production processes for fine chemicals.
Permeability studies on horse liver alcohol dehydrogenase (HLAD) in polyacrylamide gel beads
Authors: Gorrebeeck C. , Lemière G. L. , Dommisse R. A. , Lepoivre J. A. , Alderweireldt F. C. , Spanoghe M. , Lanens D. 
Published: September 2010

AbstractPolyacrylamide gel beads with monomer concentrations ranging from 5 to 30% and with constant degree of cross‐linking (5%) were prepared. Dried beads were swollen in buffered HLAD/NAD+ solutions and placed in a water‐immiscible organic solution of substrates. Increased enzymatic activity was observed in beads with higher polymer density. Evidence is given that catalyst in the high‐density polymer is concentrated in the outer part of the beads, but is homogeneously distributed in low‐density polymers. This was clearly visualised by high‐resolution NMR imaging on gel beads impregnated with Gd‐DTPA‐labeled HLAD. Furthermore, reaction rates were higher for larger beads.
Enzymatic preparation of acylglycerols of high optical purity
Authors: Ghisalba Oreste , Lattmann René , Gygas Daniel 
Published: September 2010

Abstract(S)‐3‐O‐acyl‐2‐O‐benzylglycerols with an optical purity of > 98% ee can be prepared in high yield by transesterification in a solvent free system using Pseudomonas fluorescens lipase.
Facile formation of amide bonds between fragments containing unmasked imidazole‐ring systems. Synthesis of N‐[N‐[[[(5‐methyl‐4‐imidazolyl)methyl]thio]acetyl]‐L‐methionyl]histamine
Authors: Modder Johan F. , de Klerk‐Engels Barbara , Ankersmit Hubertus A. , Vrieze Kees , van Koten Gerard 
Published: September 2010

AbstractThe synthesis is reported of the optically pure title compound [α20 −2.31 l·mol−1·dm−1] from a sequence of reactions involving 5‐methyl‐4‐imidazolemethanol, mercaptoacetic acid and (L‐methionyl)histamine. The development of a suitable synthetic route, using N‐benzyl‐2‐[[(5‐methyl‐4‐imidazolyl)methyl]thio]acetamide as a model compound, and the problems associated with the presence of imidazole ring systems in the reagents are discussed. The main problem of the synthesis, i.e., the formation of amide bonds between reagents that contain unmasked imidazole functions, is overcome by using an N,N′‐dicyclohexylcarbodiimide‐activated and N‐hydroxybenzotriazole‐moderated coupling procedure.The present method seems generally applicable and yields gram quantities in an overall yield of more than 30%, without the need for chromatography techniques.
Synthesis and spectroscopy of chemically modified spheroidenes
Authors: Gebhard R. , van Dijk J. T. M. , van Ouwerkerk E. , Boza M. V. T. J. , Lugtenburg J. 
Published: September 2010

AbstractThe syntheses and spectroscopic properties of the all‐E isomers of 11′,12′‐dihydrospheroidene (2), 3,4,11′,12′‐tetrahydrospheroidene (3), 3,4‐dihydrospheroidene (4), 3,4,5,6‐tetrahydrospheroidene (5), 3,4,7,8‐tetrahydrospheroidene (6) and 15,15′‐didehydrospheroidene (7) are described. Spheroidenes 2‐6 have the same overall shape as native spheroidene (1), which is the carotenoid bound in the photosynthetic reaction centre of Rhodobacter sphaeroides 2.4.1, but they have instead polyene chromophores of nine (4), eight (2, 5) or seven (3, 6) conjugated double bonds. In 7, the central double bond is substituted by a triple bond. The observed λmax values of 2‐6 are generally in good agreement with those calculated via the Fieser‐Kuhn rules. In the mass spectra of 2‐6, fragments due to bis‐allylic fragmentation occur, whereas 1 and 7 do not show this type of fragmentation. A detailed analysis of the 1H‐ and 13C‐NMR spectra of 1‐7 has been achieved by mutual comparison.
Selectivity in reductive elimination from dialkyl(aryl)palladium(IV) complexes, and the observation of benzyl halide transfer from palladium(IV) to palladium(II). The X‐ray structure of methyl(phenyl)(2,2′‐bipyridyl)palladium(II)
Authors: Markies Bertus A. , Janssen Maurits D. , Boersma Jaap , van Koten Gerard , Canty Allan J. , Spek Anthony L. 
Published: September 2010

AbstractThe first arylpalladium(IV) complexes, [PdXMePhR(bpy)] (bpy = 2,2′‐bipyridyl), have been isolated upon oxidative addition of methyl iodide or benzyl bromide to [PdMePh(bpy)]. These dialkyl(aryl)palladium(IV) complexes undergo reductive elimination in solution at ca. 0 °C: [PdBrMePh(CH2Ph)(bpy)] decomposes quantitatively into [PdBr(CH2Ph)(bpy)] and toluene whereas [PdIMe2Ph(bpy)] gives ethane and toluene in 4: 1 ratio together with the corresponding complexes [PdIR(bpy)] (R = Me or Ph). The reaction of methyl iodide with [PdMePh(tmeda)] at 0 °C yields ethane and [PdIPh(tmeda)] without detection of a palladium(IV) intermediate. No reaction of [PdMePh(tmeda)] with benzyl bromide was observed. The first demonstration that organic groups can be transferred from palladium(IV) to palladium(II) is reported. The molecular structure of [PdMePh(bpy)] in the solid state has been determined.
Review of 1H‐ and 13C‐NMR data on homo‐, co‐ and terpolyamides in solution
Authors: van der Velden Geert , Beulen Jo , de Keijzer Henk 
Published: September 2010

AbstractThis paper is a review of ID‐ and 2D‐NMR studies on polyamides in solution. This review includes the effects of the choice of solvent on NMR spectra, possibilities of sequence analysis in co‐ and terpolyamides using either 1H‐ or 13C‐NMR spectroscopy, discrimination between polyamide blends and copolyamides, and observation of cyclic polyamide species in a linear poly‐amide matrix.
A convenient synthesis of aziridine‐2‐carboxylic esters
Authors: Legters Johan , Thijs Lambertus , Zwanenburg Binne 
Published: September 2010

AbstractOptically active oxirane‐2‐carboxylic esters, prepared from allylic alcohols employing the Sharpless epoxidation, were treated with sodium azide. The azido alcohols obtained were subsequently converted into aziridine‐2‐carboxylic esters by reaction with triphenylphosphine, in good yields and with high optical purity. Various racemic oxirane‐2‐carboxylic esters were subjected to the same sequence of reactions.
UV spectroscopy and structures of α‐bis(methoxyimino)alkanes
Authors: Stunnenberg Frank , Cerfontain Hans , Goubitz Kees , Heydenrijk Dick , Stam Caspar H. 
Published: September 2010

AbstractThe UV spectra of the geometric isomers of the α‐bis(methoxyimino)alkanes I‐8 and the structurally related conjugated (methoxyimino)isoxazolines 11 and 13 all exhibit a ππ* absorption band, of which the maxima with cyclohexane as solvent are between 216 and 268 nm, and 258 and 282 nm, respectively. The differences in λmax are discussed in terms of variations in the degree of inter‐iminyl conjugation, as a result of (i) variations in the inter‐iminyl dihedral angle due to steric hindrance and (ii) variations in the ring strain and/or the dipolar repulsion of the two methoxyimino moieties, as with the three geometric isomers of the four‐membered ring compound 1. The lower λmax of (E,E)‐8 compared to (E,E)‐4 is ascribed to a lower degree of cross‐conjugation of the phenyl group with the planar α‐bis(methoxyimino) chromophore in the former compound; the absorption band of (E,E)‐8 is, in fact, similar to that of the aliphatic (E,E)‐5. The energy of the ππ* absorption maximum of the (E,E)‐α‐bis(methoxyimino)alkanes appears to be linearly related to that of the corresponding (E)‐α‐oxo oxime ethers with a slope close to unity, illustrating that the sensitivity for structural variations is very similar for the two types of compounds.X‐ray structure analysis showed the O‐N = C‐C = N‐O chromophore of (E,E)‐5, (E,E)‐8 and the (hydroxyimino)isoxazoline (E)‐10 in the crystalline state to be all planar within the limits of detection.
Synthesis of functionalized amino acids by ring‐opening reactions of aliphatically substituted aziridine‐2‐carboxylic esters
Authors: Legters Johan , Willems Johannes G. H. , Thijs Lambertus , Zwanenburg Binne 
Published: September 2010

AbstractNucleophilic ring‐opening reactions of 3‐alkylaziridine‐2‐carboxylic esters are described. Without ring activation at nitrogen, ring opening could only be accomplished with ethereal hydrogen chloride. Introduction of electron‐withdrawing activating groups at the nitrogen atom was necessary. Three types of activating groups were used, viz. acyl, alkoxycarbonyl and sulfonyl groups. In the presence of a Lewis‐acid catalyst, ring opening with two nucleophiles, namely indole and benzenethiol, could be accomplished. SN2‐type attack at C3 was observed exclusively. With Brönsted acids (hydrogen chloride, formic acid, acetic acid), ring opening could also be effected. 3‐Formyloxy derivatives could also be prepared by reaction of the activated aziridines with N,N‐dimethyl‐formamide in the presence of boron trifluoride etherate. Reaction with sodium azide caused some difficulties; complex product mixtures were usually obtained. N‐Sulfonylaziridine‐2‐carboxylic esters gave a mixture of the two possible regioisomers, resulting from attack at C2 and C3. Treatment of N‐sulfonylaziridine‐2‐carboxylic esters with trimethylsilyl azide, however, gave products exclusively ring‐opened at C2. On reaction of the activated aziridines with acetonitrile in the presence of boron trifluoride etherate, a ring‐expansion reaction was observed, leading to imidazolines. On standing, these heterocyclic compounds slowly hydrolyzed to α,β‐diamino carboxylic acid derivatives.
Steric perturbation of the conjugated triene chromophore. Conformational analysis of (E)‐ and (Z)‐3‐methyl‐1,3,5‐hexatriene and (Z)‐3‐tert‐butyl‐1,3,5‐hexatriene
Authors: Brouwer A. M. , Bezemer L. , Jacobs H. J. C. 
Published: September 2010

AbstractA theoretical and NMR‐spectroscopic conformational analysis is presented of the 3‐methyl‐1,3,5‐hexatrienes and of (Z)‐3‐tert‐butyl‐1,3,5‐hexatriene. It is shown that (E)‐3‐methyl‐1,3,5‐hexatriene exists mainly as the tEt rotamer and (Z)‐3‐methyl‐1,3,5‐hexatriene as the tZt rotamer. Indications are found for steric strain involving the methyl group of the E isomer. In contrast to earlier theoretical predictions, this strain does not lead to detectable amounts of s‐cis rotamers. Ab‐initio calculations reported here agree with this experimental finding, but MMP2 calculations underestimate the energy of the s‐cis form.1H NMR relaxation rates and Nuclear Overhauser Enhancements (NOE) are shown to allow a reliable determination of the predominant ground‐state conformation of alkyl‐substituted hexatrienes.NOE experiments on (Z)‐3‐ter‐butyl‐1,3,5‐hexatriene reveal that a tert‐butyl group changes the preferred conformation from tZt to cZt but, surprisingly, is unable to completely counteract the strong intrinsic preference for a spatially extended s‐trans,s‐trans conformation. We estimate the rotamer population as cZt/tZt = 80/20 (± 5).
Near absolute regio‐, diastereo‐, and enantioselectivity in a palladium catalyzed alkylation using an uncommon chiral auxiliary
Authors: Sjouken Ronald , Ebens Rijko , Kellogg Richard M. 
Published: September 2010

AbstractCondensation of R‐(+)‐1‐(2‐chlorophenyl)‐2,2‐dimethyl‐propan‐1,3‐diol (2) with a derivative (1) of 1‐formylcyclohexene substituted in the 3‐position with an acetoxy group proceeded with absolute stereospecificity at the acetal center. Catalytic alkylation of the π‐allyl complex obtained upon reaction with Pd with the anion of dimethylamalonate proceeded at the 3‐position of the cyclohexyl ring with complete stereocontrol.
Reactions of sulfur trioxide with benzene derivatives containing a deactivating oxy substituent
Authors: Ansink Harold R. W. , Cerfontain Hans 
Published: September 2010

AbstractThe reactions of phenyl acetate (2), (trifluoromethoxy)benzene (3), (difluoromethoxy)‐benzene (4), 4‐(trifluoromethoxy)phenol (5), 4‐(trifluoromethoxy)phenyl methanesulfonate (6), 4‐(trifluoromethoxy)anisole (7) and 3‐(trifluoromethoxy)anisole (8) with SO3, in nitromethane have been studied. Upon reaction with SO3, 2 yields 2‐4‐sulfonic acid (2‐4‐S); subsequently, transfer of the acetyl group takes place to yield the mixed anhydride of phenol‐4‐pyrosulfonic acid and acetic acid (9) or the corresponding hydrogen sulfate 10, depending on the amount of SO3, used. Reaction of the α‐fluorinated anisoles 3 and 4 with SO3 leads to sulfonation at the 4‐position only; however, on using both a high substrate concentration and an excess of SO3, some 2,4‐S2, is formed with 4 but not with 3.On reaction of 5 with 0.8 mol‐equiv of SO3, in C2H3NO2, the hydrogen sulfate derivative (5‐O‐S) is formed; at 100°C, some isomerization to 5‐2‐S occurs. Upon reaction with 4.0 mol‐equiv of SO3, the initially formed hydrogen sulfate slowly yields the corresponding 2‐sulfophenyl hydrogen sulfate (5‐O,2‐S2). On using 6.0 mol‐equiv of SO3, the 5‐O,2‐S2 is slowly converted into 6‐(trifluoro‐methoxy)benzo‐1,3,2,4‐dioxadithiin 2,2,4,4‐tetraoxide (11). Reaction of 6 with either 0.9 or 3.0 mol‐equiv of SO3, initially leads to insertion of sulfur trioxide in between the SO2CH3, and the adjacent O, yielding the 4‐(trifluoromethoxy)phenyl methanepyrosulfonate 12. This species subsequently yields 13 and 14. Reaction of 7 with SO3 leads to sulfonation only at the 2‐position; eventually some sulfodemethylation to yield 5‐2‐S takes place. Reaction of 8 with 1.0 mol‐equiv of SO3, yields a 68: 32 mixture of 8‐4‐S and 8‐6‐S.
Solid‐phase synthesis of oligodeoxynucleotides containing 6‐O‐alkylguanosines
Authors: Roelen H. C. P. F. , Brugghe H. F. , van den Elst H. , Klein J. C. , van der Marel G. A. , van Boom J. H. 
Published: September 2010

AbstractHigh‐quality oligodeoxynucleotides having an 6‐O‐alkyl‐2′‐deoxyguanosine (alkyl = methyl, ethyl, n‐propyl or n‐hexyl) residue at a predetermined position can be obtained via a solid‐phase approach using the respective 2‐cyanoethyl N,N‐diisopropylphosphoramidites of 5′‐O‐(4.4′‐dimethoxytrityl)‐protected 6‐O‐alkyl‐2′‐deoxyguanosines having a free exocyclic amino group, and 5′‐O‐(4‐4′‐dimethoxytrityl) N‐acyl‐protected (i.e., benzoyl and isobutyryl for dC/dA and dG, respectively) 2′‐deoxynucleosides.
Competing concepts in CAOS
Authors: Dengler Alf , Fontain Eric , Knauer Michael , Stein Natalie , Ugi Ivar 
Published: September 2010

AbstractThe evolution of Computer‐Assisted Organic Synthesis (CAOS) is briefly reviewed. The underlying concepts and strategies of the various approaches to CAOS are compared. A status report is given on bilateral synthesis design. This requires selection of suitable starting materials from a list of available compounds according to structural features of the target by correlation of substructures, augmentation of the target molecule by co‐products to yield an Ensemble of Molecules (EM) that is isomeric to the starting EM and, finally, establishment of synthesis routes that lead from the starting EM to the target EM. Despite of its apparent complexity, bilateral CAOS is a promising approach because of its combinatorial advantages.
A collection of computer methods for synthesis design and reaction prediction
Authors: Gasteiger J. , Ihlenfeldt W. D. , Röse P. 
Published: September 2010

AbstractA series of computer methods is presented that elucidate relationships between the target molecule, precursors, and starting materials of a synthesis. Both retrosynthetic and synthetic searches are performed to find the most rewarding pathways for the synthesis of complex organic structures including their stereochemical features. A user interface has been developed that allows easy switching between the various search methods and the results can be presented graphically. A system for reaction prediction has been developed that can predict the course and products of organic reactions to various depth of chemical knowledge, from the generation of isomers, up to the calculation of absolute rate constants.