Molecular mechanics analysis of the conformations of thymidine and implications for the design of anti-AIDS drugs

The steric energies of a number of the conformations of thymidine, derived from appropriate crystal structures, have been determined with the MM2 molecular mechanics force field. With one exception, these have very similar values which are close to 120 kJ mol^–1. The C2-exo/C3-endo conformation has a far higher value of 240 kJ mol^–1. The C3-endo conformation has previously been associated with thymidine derivatives which do not exhibit anti-HIV activity, and it may be that this is due to the relatively low predicted stability.     

Relative Stabilities and Molecular Structures of the Geometrical Isomers of α,α′-Dioxasubstituted Cycloalkylidenecycloalkanes. A DFT Study

The relative stabilities and molecular structures of the geometrical isomers of seven ,-dioxa derivatives of cycloalkylidenecycloalkanes with 3to 6-membered rings have been studied by DFT calculations at the B3LYP/6-31G* level of theory. In each case, the E form was calculated to have the lower total energy. The relative energy of the Z isomer proved to increase regularly with increasing sizes of the two heterocyclic rings, ranging from 1.1 to 13.8 kJ mol^–1 on going from the 3,3to the 6,6-membered rings. Intermediate values of the relative energy were calculated for the Z forms of compounds containing two dissimilar rings. The relative energy of the Z isomer was found to be proportional to d ^–9.3, where d = the distance separating the two O atoms of the Z compound. The molecular structures, electric dipole moments, and atomic charges on the O atoms are also discussed.     

Kinetics of the displacement of aqua ligands from cis-diaqua(ethylenediamine)-platinum(II)perchlorate by adenosine 5′-monophosphate in aqueous medium

The kinetics of the interaction of adenosine 5-monophosphate (5-AMP) with cis-[Pt(en)(H₂O)₂]²⁺ have been studied spectrophotometrically as a function of [Pt(en)(H₂O)₂]²⁺, [5-AMP] and temperature at pH 4.0, where the substrate complex exists predominantly as the diaqua species. Both N1 and N7 donor sites of 5-AMP are active for coordination to Pt at this pH. Base stacking and metal-induced macrochelate formation of 5-AMP plays a vital role in determining the concentration limit of 5-AMP during kinetics. Substitution occurs in two consecutive steps; both dependent on the 5-AMP concentration. Activation parameters for both steps have been calculated. The low H ₁ (42.76 ± 1.64 kJ mol^–1) and large negative values of S ₁ (–112.1 ± 5.1 J K^–1 mol^–1) as well as H ₂ (58.1 ± 1.4 kJ mol^–1) and S ₂ (–84.2 ± 4.4 J K^–1 mol^–1) indicate associative modes of activation for both ligand substitution processes in the two consecutive steps.     

Enthalpies of formation and O-O and C-O bond strengths in polyoxides RO x R′ and RO x

Bond strengths in RO-OOR, ROO-OH, and ROO-OOR (R, R = H, Me, Et, and Bu) molecules, calculated by the semiempirical quantum-chemical methods, were used to determine the enthalpies of formation of polyoxides RO _x R (x = 3, 4) and related radicals and the bond strengths (D/kcal mol^–1) in these molecules:D(ROOO-OR) = 33.2±0.9,D(ROOO-OH) = 37.5±0.7,D(R-O _x R) = 76.0±1.2,D(H-000) = 58.6,D(R-000) = 42.8±0.8. A new value of Benson's polyoxide thermochemical increment, _f H°[O-(O)₂] = 11.1±1.0 kcal mol^–1, was suggested.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2190–2193, September, 1996.     

Spectrochemistry of solutions,part 23. Changes of enthalpy and entropy in the formation of contact ion pairs: A vibrational spectroscopic appraisal using thiocyanate and azide solutions

Summary The vibrational spectra of solutions have been analyzed to assess both qualitatively and quantitatively the changes in enthalpy and entropy for ion pair formation in solutions of LiNCS, Mg(NCS)₂, and LiN₃ in liquid ammonia, dimethylformamide, dimethylsulphoxide and acetonitrile. Contrary to predictions both the H _ass and S _ass terms are all positive in the cases examined, indicating that the driving force in the ion association process derives from solvent-solute restructuring, and not the energy of the interaction between the cation and anion. This characteristic of contact ion pair formation is likely to be found to be applicable over a wide range of solvents. The following specific values of the thermodynamic parameters at 298 K have been obtained: LiNCS/DMF, G=–1.3 (1) kJ mol^–1, H _ass =+1.8 (5) kJ mol^–, S _ass =+10 (2) J mol^–1 K^–1; LiNCS/DMSO, G=+0.9 (2) kJ mol^–1, H _ass =+0.3 (3) kJ mol^–1; Mg(NCS)₂/DMF, G _ass =–4.0 (3) kJ mol^–1, H _ass =+15 (4) kJ mol^–1, S=+64 (17) kJ mol^–1; LiN₃/DMSO, G _ass =–2.5 (3) kJ mol^–1, H _ass =+4.9 (9) kJ mol^–1, S _ass =+25 (10) J K^–1 mol^–1.Submitted to celebrate the 70th Birthday of Professor Viktor Gutmann, and in recognition of his considerable contributions towards the better understanding of Chemistry in the Solution Phase     

Neue Siderophore des Pyoverdin-Typs ausPseudomonas fluorescens

Summary The structure of four new pyoverdins (Pf12-IA, -IIA, -IB und IIB) isolated from the culture medium ofPseudomonas fluorescens 12 was elucidated by combination of spectroscopic methods and degradation reactions. The pyoverdins comprise (1S)-5-amino-2,3-dihydro-8,9-dihydroxy-1H-pyrimido[1,2-a]quinoline-1-carboxylic acid whose amino group carries a 3-carboxypropanoyl-(IA), succinamoyl- (IIA), 4-carboxy-4-oxobutanoyl- (IB) or L-4-amino-4-carboxybutanoylresidue (II B) and whose carboxyl group is bound amidically to the N-terminus of D-Ser-L-Lys-Gly-. According to the short-hand-nomenclature suggested in [2, 3] the pyoverdins may be described as pyoverdin-Q-sKGOsSGK*oES*-SUC(IA), pyoverdin-Q-sKGOsSGK*o-ES*-SUCA (IIA), pyoverdin-Q-sKGOsSGK*oES*-KGL (IB) and pyoverdin-Q-sKGOsSGK*oES*-GLU (IIB). The pyoverdins described here possess the most complex structure encountered so far as their peptide part comprises eleven amino acids and the cyclo-tetrapeptide substructure. In addition, they are of special interest as for the first time glutamic acid could be identified as a chromophore side chain which is the key compound for the citric acid cycle to which belong all dicarboxylic acids found so far in pyoverdins.

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Verwendete Abkürzungen ASK Acylseitenkette - Chr Chromophor1 a - (HO)Chr Chromophor1 b - Dns Dansyl-Rest - DP Dansylpeptid - EDTA Ethylendiamintetraessigsäure - FAB Fast Atom Bombardment (PI=positive Ionen) - (HO)Orn N⁵-Hydroxyornithin - (CHO, HO)Orn N⁵-Formyl-N⁵-hydroxyornithin - PITC Phenylisothiocyanat - RP-HPLC Reversed-Phase High Performance Liquid Chromatography - Kgl -Ketoglutarsäure bzw. 4-Carboxy-4-oxobutanoyl-Rest - R _t Retentionszeit - Suc Bernsteinsäure bzw. 3-Carboxypropanoyl-Rest - Suca Succinamoyl-Rest - Suci Succinimido-Rest - TAB Trifluoracetyl-n-butylester - TEA Triethylamin     

Kinetics and mechanism of the oxidation of [N-(2-hydroxy-ethyl)ethylenediamine-N,N′,N′-triacetatocobalt(II)] by vanadate ion

The kinetics of oxidation of Co^IIHEDTA {HEDTA = N-(2-hydroxyethyl)ethylenediamine-N,N,N-triacetic acid} by vanadate ion have been studied in aqueous acid in the pH range 0.75–5.4 at 43–57 °C. The reaction exhibits second-order kinetics; first-order in each of the reactants. The reaction rate is a maximum at pH = 2.1. A mechanism is proposed in which the species [Co^IIHEDTA(H₂O)]^– and VO₂ ⁺ react to form an intermediate which decompose slowly to give pentadentate Co^IIIHEDTA(H₂O) and V^IV as final products. The rate law was derived and the activation parameters calculated: H* = 26.96 kJ mol^–1 and S* = –311.08 JK^–1 mol^–1.     

X-ray structural studies of several novel nitrocyclopropanes

The x-ray crystal structures forcis,cis- andtrans,trans- 2,3-dimethyl-1-nitrocyclopropanecarboxylic acid, 2,2,3,3-tetramethyl-1-nitrocyclopro-panecarbonitrile, 2,2,3,3-tetramethyl-1-nitrocyclo-propanecarboxamide, andtrans,trans,trans,trans-2,2,3,3-tetramethyl-1,1-dinitrobicyclopropyl are reported. Contrary to expectations, -accepting groups that are syn to dimethyl substituents prefer a conformation perpendicular to the three-membered ring when there is an sp² electron-withdrawing substituent also bonded to the same carbon atom. Ab initio calculations are reported for model compounds and these results are compared with the experimentally determined ones.     

Synthesis of some 5′-O-amino acid derivatives of uridine as potential inhibitors ofUDP-glucuronosyltransferase

Summary In an attempt to develop potential inhibitors ofUDP-glucuronosyltransferase, some 5-O-amino acid derivatives of uridine were synthesized. N-protectedL-amino acids were coupled at the 5-O-position of 2,3-O-isopropylideneuridine by esterification employing the method of symmetrical anhydrides in presence of 4-dimethylaminopyridine, 5-O-(N-benzyloxycarbonyl-O-tert.butyl-L-threonl)-23-O-isopropylideneuridine (1), 5-O-(N-tert.butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylideneuridine and (2), 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (3), and 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (4) were obtained in good yield after column chromatography on silica gel. The treatment of2 withTFA/CH₂Cl₂ (6:1) at room temperature for 30 min led to a selective removal of theBoc group without deblocking of the 2,3-O-isopropylidene group of uridine. Treatment of2 withTFA/H₂O (5:1) at room temperature for 1 h, however, released bothBoc and 2,3-isopropylidene groups. TheZ group of1 was deprotected by catalytic hydrogenolysis over 10% Pd/C/ammonium formate.

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Synthese von 5-O-Aminosäurederivaten des Uridins als potentielle Inhibitoren derUDP-Glukuronosyl-Transferase

Zusammenfassung In einem Versuch, potentielle Inhibitoren derUDP-Glukuronosyl-Transferase zu entwickeln, wurden einige 5-O-Aminosäurederivate des Uridins synthetisiert. N-GeschützteL-Aminosäuren wurden durch Veresterung mit der 5-O-Position des 2,3-isopropylidenuridins gekuppelt (Methode der symmetrischen Anhydride in der Gegenwart von 5-Dimethylaminopyridin). Solcherweise wurden 5-O-(N-Benzyloxycarbonyl-O-tert.butyl-L-threonly)-2,3-O-isopropylidenuridin (1), 5-O-(N-tert.Butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylidenuridin (2), 5-O-(N-tert.Butyloxycarbonyl-L-leucyl)-2,3-O-isopropylidenuridin (3) und 5-O-(N-tert.Butyloxycarbonyl-L-valyl)-2,3-O-isopropylidenuridine (4) nach Säulenchromatographie (Kieselgel) in guter Ausbeute hergestellt. Die Behandlung von2 mitTFA/CH₂Cl₂ (6:1) bei Zimmertemperatur (30 min) führte zu einer selektiven Abspaltung derBoc-Gruppe ohne Deblockierung der 2,3-O-Isopropylidengruppe des Uridins. Eine Behandlung von2 mitTFA/H₂O (5:1) bei Zimmertemperatur für 1 Stunde führte hingegen zur Abspaltung sowohl derBoc als auch der 2,3-O-Isopropylidengruppe. DieZ-Gruppe von1 wurde durch katalytische Hydrogenolyse auf 10% Pd/C/Ammoniumformiat abgespalten.

     

High levelab initio stabilization energies of benzene

Summary G2 theory is shown to be reliable for calculating isodesmic and homodesmotic stabilization energies (ISE and HSE, respectively) of benzene. G2 calculations give HSE and ISE values of 92.5 and 269.1 kJ mol^–1 (298 K), respectively. These agree well with the experimental HSE and ISE values of 90.5±7.2 and 268.7±6.3 kJ mol^–1, respectively. We conclude that basis set superposition error corrections to the enthalpies of the homodesmotic or isodesmic reactions are not necessary in calculations of the stabilization energies of benzene using G2 theory. The calculated values of the enthalpies of formation of such molecules containing multiple bonds such as benzene ands-trans 1,3-butadiene, which are found from the enthalpies of isodesmic and homodesmotic reactions rather than of atomization reactions, demonstrate good performance of G2 theory. Estimates of theH _f ^o value for benzene from the G2 calculated enthalpies of homodesmotic reaction (2) and isodesmic reaction (3) are 80.9 and 82.5 kJ mol^–1 (298 K), respectively. These are very close to the experimentalH _f ^o value of 82.9±0.3 kJ mol^–1. TheH _f ^o value ofs-trans 1,3-butadiene calculated using the G2 enthalpy of isodesmic reaction (4) is 110.5 kJ mol^–1 and is in excellent agreement with the experimentalH _f ^o value of 110.0±1.1 kJ mol^–1.     

Preparation,thermal decomposition process and kinetics for terbium<Emphasis Type="Italic">p</Emphasis>-methoxybenzoate ternary complex with 1,10-phenanthroline

The complex of [Tb₂(p-MOBA)₆(PHEN)₂] (p-MOBA=C₈H₇O₃,p-methoxybenzoate; PHEN=C₁₂H₈N₂, 1,10-phenanthroline) was prepared and characterized by elemental analysis and IR spectroscopy. The thermal behavior of Tb₂(p-MOBA)₆(PHEN)₂ in a static air atmosphere was investigated by TG-DTG, DTA, SEM and IR techniques. By the kinetic method of processing thermal analysis data put forward by Malek et al., it is defined that the kinetic model for the first-step thermal decomposition is SB(m,n). The activation energy E for this step reaction is 140.92 kJ mol^-1, the enthalpy of activation H is 136.06 kJ mol^-1, the Gibbs free energy of activation G is 145.16 kJ mol^-1, the entropy of activation S is -15.53 J mol^-1, and the pre-exponential factor lnA is 29.26. The lifetime equation at mass loss of 10% was deduced as ln =-28.72+1.943·10⁴/T by isothermal thermogravimetric analysis.     

Spectrophotometric determination of vanadium with 4-(1′H-1′,2′,4′-Triazolyl-3′-azo)-2-methylresorcinol

Summary 4-(1H-1,2,4-Triazolyl-3-azo)-2-methylresorcinol reacts with vanadium(V) at pH 8.10 (Tris-HClO₄ buffer solution) to produce a pink-violet 11 complex ( _max=525 nm,=2.55×10⁴l·mol^–1· cm^–1) in a 50% (v/v) methanol-water medium, which allows the spectrophotometric determination of 0.1 to 1.51 ppm of vanadium. The method has been applied for the determination of the vanadium content in low alloy steels.

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Spectrophotometriscbe Bestimmung von Vanadin mit 4-(1H-1,2,4-triazo-lyl-3-azo)-2-methylresorcin

Zusammenfassung Vanadin bildet bei pH 8,10 (Tris-HClO₄-buffer) mit 4-(1H-1,2,4-tri-azolyl-3-azo)-2-methylresorcin ein rosenrot-violettes Chelat, dessen Absorptionsmaximum bei 525 nm in Gegenwart von 50% Methylalkohol gemessen wird. Dieser 11-Komplex entspricht bei einer Vanadin-Konzentration von 0,1–1,51g/ml dem Beerschen Gesetz; seine molare Absorptivität ist 2,55×10⁴l·mol^–1·cm^–1. Das Verfahren wurde zur Bestimmung des Vanadins in Stahl verwendet.

     

Ab initio MP2 calculations of the products of acetylene addition to HgCl2

Gas-phase reaction of acetylene with HgCl₂ resulting in -chlorovinylmercury derivatives and their interaction with Cl^– and I^– anions and KI molecule was studied by the ab initio MP2 method with the Dunning—Hay double zeta basis set and LanL pseudopotential for Hg, K, and I atoms. The reaction was shown to proceed via a -complex of acetylene and HgCl₂ (the calculated enthalpy of formation is –6.5 kcal mol^–1). According to calculations, the activation energy of formation of cis--chlorovinylmercury chloride from acetylene and HgCl₂ is 31 kcal mol^–1. Chloride and iodide anions and KI molecule are readily added to both cis- and trans-isomer of -chlorovinylmercury chloride to give stable species.     

ESR and ENDOR Investigations on Various <Emphasis Type="Italic">Wurster</Emphasis>’s Radical Cations in Solution. Experimental Results,Theoretical <Emphasis Type="Italic">Ab Initio</Emphasis>, and DFT Calculations

Summary. ESR and ENDOR spectra are reported of several symmetrical substituted N,N,N,N-tetraalkyl-p-phenylenediamine radical cations in solution. Different N,N-alkyl substituted para-phenylenediamines, like the ethyl, n-propyl, and iso-propyl derivative are compared with the parent N,N,N,N-tetramethyl-p-phenylenediamine (Wursters Blue Cation). N,N,N,N-Tetrabenzyl-p-phenylenediamine, 1,4-dipyrrolidinylbenzene, and N,N-bis[4-(dimethylamino)phenyl]piperazine are additionally investigated. Experimental and calculated hyperfine coupling constants are compared. Characteristic UV-VIS data and redox potentials in acetonitrile are reported, together with the syntheses of the compounds.     

Kinetics of substitution of aqua ligands fromcis-diaqua-bis(ethylene-diamine) cobalt(III) ion by quinolinic acid in water-ethanol mixtures

Summary The kinetics of aqua ligand substitution fromcis-[Coen₂(H₂O)₂]³⁺ by quinolinic acid have been studied spectrophotometrically in the 40 to 55°C range. At pH 4.05 the quinolinic acid H₂Quin behaves as uninegative and bidentate (O, O) donor. The replacement of water was found to involve two consecutive step processes. The first is the replacement of one water fromcis-[Coen₂(H₂O)₂]³⁺ by unidentate HQuin^–, involving prior establishment of an ion-pairing associative equilibrium, followed by dissociative interchange. The second step is the slower chelation step, where another water molecule is replaced. The rate constants for both the steps and the ion-pair equilibrium constant for the first step have been evaluated. The activation parameters for the two steps are: H ₁ =117.2 kJ mol^–1, H ₂ =100.5 kJ mol^–1 and S ₁ =69.4 JK^–1 mol^–1, S ₂ =12.1 JK^–1 mol^–1. A probable mechanism for the substitution process is suggested.     

Optisch aktive,aromatische Spirane, 8. Mitt.: Darstellung optisch aktiver, 5, 5′, 6′-trisubstituierter 2,2′-Spirobiindane bekannter Chiralität und enantiomerer Reinheit

Starting from (+) (2R) methyl 5-ethyl-2,2-spirobiindane-5-carboxylate of known enantiomeric purity 79 optically active, configurationally correlated 5,5,6-trisubstituted 2,2-spirobiindanes (2–7) were prepared for the purpose of testing a shortened polynomal Ansatz for chirality functions. Their optical rotations and¹H-nmr spectra are reported.In this context several 6-substituted 5-ethylindanes (1) were prepared as model compounds for synthetic transformations.

     

Identification and determination of organic acids in cultivation medium ofPenicillium vermiculatum dang

Summary [2E,7E]-4,9-dioxo-2,7-decadienoic, [2E,7E]-9-oxo-2,7-decadienoic and [2Z,4E]-2-methyl-2,4-hexadienoic acids were isolated from the filtrate ofPenicillium vermiculatum Dang. The presence of [2E,2E,7S,7E]-4,9-dioxo-7-(4,9-dioxo-2,7-decadienoyloxy)-2-decenoic acid was confirmed by chromatography. HPLC was used for the determination of these acids in the cultivation medium.

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Identifizierung und Bestimmung von organischen Säuren im Kultivierungsmedium vonPenicillium vermiculatum Dang

Zusammenfassung [2E,7E]-4,9-dioxo-2,7-decadiensäure, [2E,7E]-9-oxo-2,7-decadiensäure und [2Z,4E]-2-methyl-2,4-hexa-diensäure wurden aus dem Kultivierungsmedium vonPenicillium vermiculatum Dang isoliert. Die Anwesenheit von [2E,2E,7S,7E]-4,9-dioxo-7-(4,9-dioxo-2,7-decadienoyloxy)-2-decensäure wurde chromatographisch bestätigt, Im Filtrat vonP. vermiculatum wurden diese Säuren mittels HPLC analysiert.

     

Formation Enthalpy and Entropy of Exciplexes with Variable Extent of Charge Transfer in Solvents of Different Polarity

Temperature dependence was studied for relative quantum yields of emission from some exciplexes of pyrene, 1,12-benzoperylene, and 9-cyanoanthracene with methoxybenzenes or methylnaphthalenes in solvents of different polarity (ranging from toluene to acetonitrile). The enthalpy H _Ex ^*, the entropy S _Ex ^*, and the Gibbs free energy G _Ex ^*of formation of the exciplexes were determined. Depending of the Gibbs free energy of excited-state electron transfer (G _et ^*) and solvent polarity, the values of H _Ex ^*, S _Ex ^*, and G _Ex ^*vary over the ranges from –5 to –40 kJ mol^–1, from +3 to –90 J mol^–1K^–1, and from +3 to –21 kJ mol^–1, respectively. The possibility is discussed that the effect of solvent polarity G _et ^*on the exciplex formation enthalpies can be rationalized in terms of the model of correlated polarization of an exciplex and the medium.     

Restricted helix inversion in chiral 2,18-bridged biliverdins

Summary The energy barrier to helix inversion in biliverdin is doubled if the pyrrolinone rings are bonded by a four-link chain as present in the chiral diastereoisomers of 2,18-(1,4-dimethoxybutane-1,4-diyl)-8,12-bis(2-methoxycarbonylethyl)-3,7,13,17-tetramethyl-1,19-(21H,24H)-bilindion1 and its hydroxy derivative2. The torsional restrictions thus imposed on the bilatriene moiety provide the basis for resolution by first-order asymmetric transformation with optically active mandelic acid. Interconversion barriers at 293 K range from 85 to 90 kJ mol^–1 and were determined monitoring the rate of isomerization processes (M-RR)-1 b(P-RR)-1 a, (P-SS)-1 b(M-SS)-1 a, and the racemization process (P-RS)-1 c(M-RS)-1 c by c.d. spectroscopy. Similar results were obtained with the bridged biliverdins2.

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Behinderung der Helix-Interkonversion in 2,18-überbrückten Biliverdinen

Zusammenfassung Die Energiebarriere für die Helixinversion von Biliverdinen läßt sich durch Überbrücken der Pyrrolinonringe mit einer C-4 Einheit auf das Doppelte erhöhen. Derartige Verhältnisse liegen in den chiralen Diastereomeren des 2,18-(1,4-Dimethoxybutan-1,4-diyl)-8,12-bis(2-methoxycarbonylethyl)-3,7,13,17-tetramethyl-1,19-(21H,24H)-bilindions1 und seines Hydroxyabkömmlings2 vor. Die dadurch bedingten Torsionsrestriktionen im Bilatrienteil stellen die Grundlage für eine Spaltung durch asymmetrische Umwandlung erster Art mit optisch aktiver Mandelsäure dar. Die Barrieren liegen zwischen 85 und 90 kJ mol^–1 (293 K) und wurden aus der Geschwindigkeit der Isomerisierungsprozesse (M-RR)-1 b(P-RR)-1 a, (P-SS)-1 b(M-SS)-1 a, sowie des Razemisierungsprozesses (P-RS)-1 c(M-RS)-1 c mittels Circulardichroismus bestimmt. Ähnliche Ergebnisse wurden für die Isomeren von2 erhalten.

     

An Ab Initio Study of the Relative Stabilities and Molecular Structures of 3-Substituted 2,5-Dihydrofurans and 4-Substituted 2,3-Dihydrofurans

The geometry optimized structures and total energies of 3-substituted (R) 2,5-dihydrofurans (a) and their isomers, 4-substituted 2,3-dihydrofurans (b), have been determined by ab initio calculations at the MP2/6-31G^*//HF/6-31G^* level. The nature of the moiety R has a marked effect on the relative total energies of the isomeric forms: at the calculation level cited, the reaction enthalpies for the a b isomerization range from +4.7 kJ mol^–1 for R = MeO to –30.5 kJ mol^–1 for both R = COOMe and R = NO₂. The reaction enthalpies appear to be controlled by the electronic effect of R on the strength of p- conjugation in b. The a isomer has a planar ring, independent of R (excluding NH₂), whereas the planarity of b depends on the electronic nature of R: the 2,3-dihydrofuran ring is planar for both R = COOMe and R = NO₂, but nonplanar for less conjugation-enhancing substituents.