2a 2c Research Articles

Dephosphorylation of abnormal sites of tau factor by protein phosphatases and its implication for Alzheimer's disease

The abnormally phosphorylated forms of tau factor are major constituents of neurofibrillary tangles in Alzheimer's disease brain. In order to investigate protein phosphatases which are related to dephosphorylation of abnormal phosphorylation sites, we examined the dephosphorylation of tau factor phosphorylated by three proline-directed type protein kinases. Tau factor phosphorylated by cdc2 kinase and tau protein kinase II was dephosphorylated by the holoenzyme of protein phosphatase 2A and calcineurin, while either the catalytic subunit of protein phosphatase 2A or protein phosphatase 2C could not catalyze the dephosphorylation. From the kinetic analysis, we concluded that tau factors phosphorylated by the protein kinases serve as good substrates for protein phosphatase 2A and calcineurin. On the other hand, tau factor phosphorylated by glycogen synthase kinase 3α was dephosphorylated by the catalytic subunit of protein phosphatases 2A as well as the holoenzyme of protein phosphatase 2A and calcineurin. It has been reported that serines 199, 202 and 396 according to the numbering of the longest human tau isoform are among the major abnormal phosphorylation sites of tau factor. We synthesized two phosphopeptides which contained phosphoserines 199 and 202 or phosphoserine 396 and prepared the polyclonal antibodies specific for the phosphopeptides. Using these antibodies, we confirmed that the holoenzyme of protein phosphatase 2A and calcineurin could dephosphorylate phosphoserines 199, 202 and 396 in tau factor. The catalytic subunit of protein phosphatase 2A could dephosphorylate phophoserine 396 but not phosphoserines 199 and 202. Neurofibrillary tangles in Alzheimer's disease brain were immunostained with both antibodies but the normal neurons in the normal aged brains were not. These results suggest that protein phosphatase 2A and calcineurin can be involved in the dephosphorylation of abnormal phosphorylation sites in tau factor and that the dephosphorylation of phosphoserine 396 is differently regulated from phosphoserines 199 and 202.

Mononuclear manganese(III) complexes of a heterodonor (N2OS) ligand containing thiolate-type sulfur: synthesis, structure, redox and spectroscopic properties

Two series of five-co-ordinate high-spin (S= 2) mononuclear manganese(III) complexes have been prepared of general formulae [MnL(X)](X = Cl 1a, Br 1b, NCS 1c or N31d) and [MnL(B)]CIO4[B = pyridine (py)2a, 3-methylpyridine (3Me-py)2b or 4-methylpyridine (4Me-py)2c] using methyl 2-[2-(salicylideneamino)ethylamino]cyclopent-1-ene-1-carbodithioate (H2L) as tetradentate ligand with a (N2OS)2– donor set. The complexes have been characterised by a combination of IR and UV/VIS spectroscopy, magnetic measurements and electrochemical studies. Their UV/VIS spectra show two ligand-field transitions at ca. 685 (5B1→5E) and 570 nm (5B1→5B2) along with a strong charge-transfer band in the near-UV region (ca. 440 nm), assigned as a phenolate O→Mn(dπ·) ligand-to-metal charge-transfer transition. Cyclic voltammograms of the complexes (except 1d) exhibit a one-electron quasi-reversible MnIII–MnII reduction with E½ close, to –0.12 V (vs. saturated calomel electrode). For 1a–1c irreversible MnIII–MnIV oxidation is also observed. The compounds have an axially elongated square-pyramidal structure as dictated by the Jahn–Teller effect with ligands X or B occupying the axial position. Their electronic spectra and electrochemical properties show invariance with group X (or B) in the axial position. The crystal structure of complex 1b was solved by Patterson and Fourier methods followed by a least-squares refinement to a conventional R value of 0.037. The basal plane of the five-co-ordinated manganese centre is defined by N (two), S and O atoms, derived from the ligand L. The co-ordinated S atom behaves like a thiolate anion as reflected by the C–S bond distance 1.717(9)A.

Synthesis of new macrocyclic ligands for hetero‐multinuclear transition‐metal complexes

AbstractThe [3 + 3] macrocyclic compounds 2a–2c were easily prepared by cyclization of the dialdehyde 8 with the appropiate diamines in refluxing CH3CN/MeOH (1/1), in the presence of Ba2+ as a template ion. These macrocycles contain three salen units and are therefore, in combination with the crown ether interior, potentially tetranucleating. The length of the diamine bridge and the temperature at which the reaction is carried out, appear to influence the size of the macrocycle formed. In this way, the [4 + 4] macrocycle 2d could be formed selectively over the [3 + 3] macrocycles by carrying out the reaction at room temperature.

Serotonergic control of androgen-induced dominance

The present study investigates the role of serotonergic systems in anabolic steroid-induced aggression. An animal model of aggressive dominance was used to assess the chronic effects of testosterone propionate. When rats that had become dominant following administration of testosterone propionate received serotonergic agonists with selectivity for the 5-HT 1A receptor (8-OH-DPAT, buspirone, gepirone), the 5-H 1B receptor (eltoprazine, TFMPP), or the 5- HT 2A 2C receptor (DOM), a dose-dependent decrease in dominance was demonstrated. Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and pindolol) blocked agonist-induced reductions in dominance in varying degrees. Nonserotonergic agonists with CNS depressant effects were also tested in dominant animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at doses that interfered with motor behavior. The opioid agonist, morphine, dose dependently decreased dominance, but this effect was reversible with administration of the serotonergic antagonist, pirenpirone, suggesting the antidominant effect of morphine had a serotonergic component. Biochemical experiments demonstrated that following chronic testosterone propionate, there was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the striatum or the frontal cortex. Chronic testosterone propionate also caused an increase in the affinity of [ 3H]8-OH-DPAT for the 5-HT 1A receptor but no corresponding change in the density of 5-HT 1A binding sites in the hippocampus. There was also no change in the properties of the 5-HT 2 receptor in the frontal cortex following chronic testosterone propionate. These data suggest that serotonergic systems may play an important role in the control of anabolic steroid-induced aggressive dominance.

Excitatory and inhibitory effects of serotonin on spinal axons

We studied the effects of serotonin on compound action potentials in dorsal columns isolated from young (nine to 13 days old) rats. Conducting action potentials were activated by submaximal (50%) and supramaximal constant current electrical stimuli and recorded with glass micropipettes. At 10 μM and 100 μM concentrations, serotonin significantly increased mean action potential amplitudes by9.6 ± 6.5% (± S.D., P <0.05) and16.6 ± 12.2% (± S.D., P < 0.005), respectively. Likewise, 10μM and 100μM of quipazine (a serotonhin 2A agonist) increased the amplitudes by9.6 ± 2.5% (± S.D., P < 0.0005) and37.7 ± 8.7% (± S.D., P < 0.0005), respectively. In contrast, 10 μM and 100 μM concentrations of 8-hydroxy-dipropylaminotetralin-hydrobromide (a serotonin 1A agonist) reduced axonal excitability by−9.4 ± 5.5% (±S.D., P <0.05) and−32.9 ± 10.6% (±S.D., P < 0.0005), respectively. At 50 μM concentration, mianserin (a serotonin 2A and serotonin 2C antagonist) eliminated the excitatory effects of 100 μM quipazine dimaleate. The combination of 50 μM mianserin and 100 μM serotonin reduced action potential amplitudes by−5.6 ± 4.9% (±S.D., P < 0.05). These results suggest that serotonin 1A and serotonin 2A receptor subtypes are present on spinal dorsal column axons. These two receptor subtypes have opposing effects on axonal excitability. The ratios and sensitivies of these two axonal receptor subtypes may modulate axonal excitability in rat dorsal column axons and have important implications for both development and injury of axons.

Synthesis and FKBP binding of small molecule mimics of the tricarbonyl region of FK506

Small acyclic model compounds were synthesized to examine the importance of the C(9) carbonyl group of KF506 for FKBP binding. 4-(4′-Methoxyphenyl)-1-butyl (3″, 4″, 5″-trimethoxyphenylglyoxyl) pipecolate (compound 2d), containing the N-(glyoxyl)pipecolate motif of FK506, was found to bind to FKBP with IC 50 of 16 μM. Replacement of the carbonyl group at the position corresponding to C(9) of FK506 with small nonpolar groups (hydrogen, methylene or methyl group, compounds 2a–2c) significantly reduced the binding affinity.

Disulfur-bridged complexes of molybdenum. Crystal structure of the dimolbdenum(IV) complex [{MoCl3(C4H8S)}2(µ-S2)(µ-C4H8S)] and of the MoIVMoVcomplex [(Me2S)2Cl2Mo({µ-S2)(µ-S)MoCl3(SMe2)

Treatment of [Mo(CO)6] with S2Cl2 gave a very dark green material of empirical formula Mo2S2Cl6·CH2Cl21 which, on reaction with L, gave green [{MoCl3(L)}2(µ-S2)(µ-L)](L = C4H8S 2a, PhCH2SMe 2b or C4H8O 2c), and with SMe2 gave the novel, brown, unsymmetrical, mixed-oxidation-state complex [(Me2S)2Cl2Mo(µ-S2)(µ-S)MoCl3(SMe2)]3. The structures of 2a and 3 have been established by X-ray crystallography. Compounds 2a–2c are diamagnetic and NMR data have been obtained, whereas 3 is paramagnetic and shows, in a CH2Cl2 glass at 40 K, a broad, roughly axial EPR resonance with gmax at 1.94.

Aerobic photooxidation and C–C bond cleavage of the acetylacetonate ligand in (2-arylazo)arylpalladium(II) complexes induced by visible light

(Arylazo)aryl(acetylacetonato)palladium(II) complexes [Pd(4-RC6H3NNC6H4R-4′)(O,O-acac)](R = H 1a, Me 1b or OMe 1c; Hacac = acetylacetone), upon irradiation of their acetone solutions at room temperature by UV, or even long-wavelength visible (λ > 500 nm) light, were readily oxidized by atmospheric oxygen to give the corresponding acetato derivatives [Pd(4-RC6H3NNC6H4R-4′)(µ-O2CMe)]2(R = H 2a, Me 2b or OMe 2c), providing a model for some chemical and biological processes. The oxidation reaction of complex 1b was first order in the complex when [1b]0⩽ 2 × 10–3 mol dm–3. Complexes 1b and 1c were photooxidized at approximately twice the rate of complex 1a. In the presence of a scavenger of C-centred radicals (CCl4) the rate of complex 2b accumulation was reduced. When pyridine was added or co-ordinating solvents (acetonitrile or nitromethane) were used no photooxidation of complex 1 occurred. In the presence of PPh3 an induction period was observed and the oxidation of 1 started only after all the PPh3 was oxidized under irradiation into OPPh3. Spectroscopic data suggested that these ligands inhibit this photochemical oxidation because they change the type of co-ordination of the azobenzene chromophore and/or the acac ligands inducing a disconnection between the chromophore (antenna) and the acac ligand.

Synthesis and radical polymerization of allenyl ethers with oligo(oxyethylene) moieties

AbstractSynthesis and radical polymerization of allenyl ethers with oligo(oxyethylene) moieties (1a–1c: CH2CCHO(CH2CH2O)mCH3, m = 3 − 1) were examined. The polymerization of 1a(m = 3) in bulk with 2,2′‐azoisobutyronitrile as initiator at 60°C gives the polymer 2a in 51% yield with 75% of the double bonds remaining in the polymer chain (estimated by 1H NMR). The polymers 2a–2c are hydrophilic, soluble in protic solvents such as water and methanol, and are subject to crosslinking upon storage in the air.

Diastereoface differentiation in addition of lithium enolates to chiral α,β-epoxyaldehydes

The aldolisation reaction of lithium ester enolates with chiral α,β-epoxyaldehydes 2a–2f has been investigated. The reaction proceeds with diastereofacial preference in favour of the anti isomer ( anti:syn ≈ 4:1) and can be greatly enhanced in the case of cis α,β-epoxy-aldehydes 2a–2c by a synergic effect of temperature and enolate excess ( anti:syn 13:1). The Felkin-Ahn model can explain the results obtained on asymmetric induction.

Transition-metal complexes of di- and tri-phosphines derived from 1,1-bis(diphenylphosphinomethyl)ethene

Base-catalysed rearrangements of and/or additions of PPh2H to [M(CO)4{(Ph2PCH2)2CCH2}](M = Cr 1a, Mo 1b or W 1c) lead to cis-[M(CO)4{cis-Ph2PCHC(Me)CH2PPh2}]2a–2c and to fac-single-crystal X-ray diffraction. Marked differences are seen in the chelate-ring conformations of 1b with an exocyclic CC bond. 2b with an endocyclic CC bond, and cis-[Mo(CO)4{Ph2P(CH2)3PPh2}] with no CC bond. Proton, 13C and 31P NMR data for 3b and 3c were obtained and a two-dimensional rotating frame nuclear Overhauser experiment was used to identify anisochronous methylene resonances in the proton NMR spectrum of 3b thus confirming a dependence of 3J(PH) on dihedral angle in these rigid polycyclic systems.

Asymmetric Induction in the Epoxidation of Alkenyl Glycosides of Tri‐O‐acetyl‐N‐acetyl‐β‐D‐glucosamine

AbstractThe reaction of alkenyl glycosides 2a–2c with MCPBA gives diasteroisomeric mixtures of epoxides 3 and 4. The asymmetric induction decreases in the order 2a ≫ 2b &gt; 2c. The absolute configuration of epoxyalkyl glycosides is determined by correlation with (R)‐glycerinaldehyde in an independent synthesis of 3a and 3c.

3H]‐MK 912 binding delineates two α2‐adrenoceptor subtypes in rat CNS one of which is identical with the cloned pA2d α2‐adrenoceptor

1. Simultaneous computer modelling of control and guanfacine-masked [3H]-MK 912 saturation curves as well as guanfacine competition curves revealed that the drugs bound to two alpha 2-adrenoceptor subtypes in the rat cerebral cortex with very different selectivities. These alpha 2-adrenoceptor subtypes were designated alpha 2A and alpha 2C. The Kd value of [3H]-MK 912 for the alpha 2A-subtype was 1.77 nM and for the alpha 2C-subtype 0.075 nM; the receptor sites showing capacities 296 and 33 fmol mg-1 protein, respectively. The Kds of guanfacine were 19.9 and 344 nM, respectively. 2. Binding constants of 26 compounds for the two rat cerebral cortex alpha 2-adrenoceptor subtypes were determined by simultaneous computer modelling of control and guanfacine-masked drug competition curves as well as plain guanfacine competition curves using [3H]-MK912 as labelled ligand (i.e. a '3-curve assay'). Of the tested drugs WB4101, corynanthine, rauwolscine, yohimbine, ARC 239 and prazosin were found to be clearly alpha 2C-selective with selectivities ranging from 16 to 30 fold whereas guanfacine, oxymetazoline, BRL 44408 and BRL 41992 were found to be alpha 2A-selective with selectivities ranging from 9 to 22 fold. 3. The Kds of compounds obtained for the cerebral cortex alpha 2C-adrenoceptors showed an almost 1:1 correlation with the corresponding Kds for alpha 2-adrenoceptors expressed by the pA2d-gene (the rat 'alpha 2-C4' adrenoceptor) in CHO-cells. The cerebral cortex alpha 2A-adrenoceptors did not correlate well with the pA2d alpha 2-adrenoceptor Kds. 4. In the rat spinal cord [3H]-MK 912 bound to alpha 2A- and alpha 2C-adrenoceptor sites with similar affinities as in the cerebral cortex and with densities 172 and 7.4 fmol mg-1 protein, respectively. Drug affinities for some compounds showing major selectivity for alpha 2A- and alpha 2C-adrenoceptors were fully compatible with the notion that the spinal cord sites were alpha 2A- and alpha 2C-adrenoceptors.

Benzoanellated centropolyquinanes, 11. Synthesis of tribenzotriquinacene and some centro‐substituted derivatives

AbstractThe syntheses of tribenzotriquinacene (1a) and five centro‐substituted derivatives, 1b–1e and 1g, as well as of the related diindan 13 are reported. The three‐step synthetic sequences include the reduction of suitably substituted 2‐benz‐hydryl‐1,3‐indandiones 3 to the corresponding 1,3‐indandiols 4 and the twofold cyclodehydration of the latter to close two additional five‐membered rings at a time. Although the yields of the cyclodehydration step 4 · 1 are only low to moderate (10–33%), the overall approach allows the preparation of 5–50‐gram amounts of the centropolyindans in most cases by starting from simple 1,3‐indandiones 2a–2c. This includes the new synthesis of the parent tribenzotriquinacene (1a). The related Cs‐symmetrical diindan, 4b,9,9a,10‐tetrahydroindeno[1,2‐a]indene (13), has been prepared in high yield by using the same cyclodehydration technique. Scope and limitations of the double cyclodehydration strategy are described concerning the synthesis of 1,3‐indandiones with bulky substituents at C–2 and the cyclization of 1,3‐indandiols with an aptitude to undergo heterolytic cleavage of an exocyclic C–2–C‐α bond, in particular 4f. The course of the reduction of the 2,2‐disubstituted 1,3‐indandiones with lithium aluminum hydride is discussed on the basis of the stereochemistry of the product 1,3‐indandiols.

Synthesis and characterisation of sulfur-rich manganese(III) and vanadium(IV) complexes containing dithioacid ligands

The chemistry of the bidentate (S,S′)– donor ligand 2-aminocyclopent-1-ene-1-carbodithioic acid (Hacda) and its N-alkylated derivatives [R = Et (Heacda), Prn(Hpacda), or Bun(Hbacda)] with vanadium(IV) and manganese(III) has been studied. The vanadium(IV) complexes [V(aacda)4]1a–1d are all eight-co-ordinated non-oxo species containing a VS8 chromophore. Their ESR spectra in frozen solution (140 K) exhibit axial anisotropy with a 16-line 51V hyperfine pattern. The observed order in spin-Hamiltonian parameters (g‖≈ 1.932, g⊥≈ 1.985, A‖≈ 175 × 10–4 cm–1 and A⊥≈ 74 × 10–4 cm–1) indicates a dx2–y2 ground state with a dodecahedral (D2d) structure. Electrochemical studies of 1a–1d show a quasi-reversible one-electron VIV–VIII reduction at ≈–0.7 V vs. saturated calomel electrode (SCE). The manganese(III) complexes [Mn(aacda)3]2a–2c are all high-spin species (µeff 5.01–5.10) and exhibit two ligand-to-metal charge-transfer bands at ≈ 610 and 530 nm. Their cyclic voltammograms reveal the presence of two quasi-Nernstian couples: E½(ox)= 0.1 V and E½(red)=–0.33 V vs. SCE due to MnIV–MnIII and MnIII–MnII electron transfers respectively.

Identification of the major protein phosphatases in mammalian cardiac muscle which dephosphorylate phospholamban

The protein phosphatases which dephosphorylate native, sarcoplasmic reticulum (SR)-associated phospholamban were studied in cardiac muscle extracts and in a Triton fraction prepared by detergent extraction of myofibrils, the latter fraction containing 70-80% of the SR-associated proteins present in the tissue. At physiological concentrations of free Mg2+ (1 mM), protein phosphatase 1 (PP1) accounted for approximately 70% of the total phospholamban phosphatase activity in these fractions towards either Ser-16 (the residue labelled by cAMP-dependent protein kinase, PK-A) or Thr-17 (the residue phosphorylated by an SR-associated Ca2+/calmodulin-dependent protein kinase). Protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) accounted for the remainder of the activity. A major form of cardiac PP1, present in comparable amounts in both the extract and Triton fraction, was similar, if not identical, to skeletal muscle protein phosphatase 1G (PP1G), which is composed of the PP1 catalytic (C) subunit complexed to a G subunit of approximately 160 kDa, responsible for targeting PP1 to both the SR and glycogen particles of skeletal muscle. This conclusion was based on immunoblotting experiments using antibody to the G subunit, ability to bind to glycogen and the release of PP1 activity from glycogen upon incubation with PK-A and MgATP. PP1 accounted for approximately 90% of the phospholamban (Ser-16 or Thr-17) phosphatase activity in the material sedimented by centrifugation at 45,000 x g, a fraction prepared from cardiac extracts which is enriched in SR membranes. The G subunit in this fraction could be solubilised by Triton X-100, but not with 0.5 M NaCl or digestion with alpha-amylase, indicating that it is bound to membranes and not to glycogen. By analogy with the situation in skeletal muscle, the PK-A catalysed phosphorylation of the G subunit, with ensuing release of the C subunit from the SR, may prevent PP1 from dephosphorylating SR-bound substrates and represent one of the mechanisms by which adrenalin increases the phosphorylation of cardiac phospholamban (Ser-16 and Thr-17) in vivo. Hearts left in situ post mortem lose 85-95% of their PP1 activity within 20-30 min. This remarkable disappearance of PP1 may partly explain why the importance of this enzyme in cardiac muscle metabolism has not been recognized previously.

Polymer bound pyrrole compounds, VII: Xanthobilirubinic acid esters and amides from an insoluble, polystyrene-supported precursor

A series of xanthobilirubinic acid (XBR) esters (i.e.,1c to1p) and amides (2a–2c) have been prepared by a procedure involving detachment of the chromophore previously ester-bound to a functionalized, insoluble polystyrene (1b). Detachment is achieved by treatment with the respective alcohol in aqueous alkali or with the amines, yielding directly the corresponding esters or amides. With primary, short-chained alcohols the ester yields are high (60% forn-C4H9-OH to 99% for C2H5-OH), but decrease rapidly with chain length (40% forn-C10H21-OH and 0% forn-C16H33-OH). The same trends are observed with the amines. These results are interpreted in terms of an (increasingly) unfavourable entropic interaction between the polymer matrix to which the chromophore is bound and the (growing) alcohol chain. The impairment by the long chained nucleophile to reach the transesterification center could also contribute, and, for the most lipophylic alcohols, their low solubility in aqueous alkali is an additional drawback. With secondary and tertiary alcohols, no ester is obtained, in agreement with a BAC2 mechanism involving a tetrahedral intermediate.

Reactions of nitrile oxides and nitrile imines with 4‐arylidene‐2‐phenyl‐5(4H)‐thiazolones

AbstractNitrile oxides 2a, b and nitrile imines 2c–e are added to the C  C bond of 4‐arylidene‐2‐phenyl‐5(4H)‐thiazolones 1 to afford spiro‐isoxazolines 3a–d and spiro‐pyrazolines 3e–j, respectively. The cycloaddition reactions are regioselective and only one of the two possible regioisomers is isolated. Reactions of the cycloadducts with nucleophiles lead to isoxazole and pyrazole derivatives 8 and 10 by opening of the thiazolone ring.

Bildung von μ-oxo-bis(η 5-cyclopentadienyldichlorotitan(IV)) aus η 5-cyclopentadienyl-tris(methylselenolato)titan(IV)

The recrystallization of CpTi(SeCH 3) 3 ( 1) from methylene chloride/pentane (1 : 1) in the presence of traces of moisture over a period of 18 months at −18° C afforded the species [CpTiCl 2] 2O ( 2a) (65%), CpTiCl 3 ( 2b) (10%) and [CpTiOCl] 2 ( 2c) (25%). 2a–2c were characterized from their 1H NMR and mass spectra. 2a crystallizes in the space group P2 1/ c with a = 9.454(7), b = 12.080(5), c = 13.060(6) Å, β = 96.38(5)° and Z = 4.

The Thermal and Photochemical Behavior of the Cyclomers Derived from 1,1′-(1,3-Propanediyl)bis(pyridinyl) Diradicals

Abstract Reduction of 1,1′-(1,3-propanediyl)bis(pyridinium) dibromide (5a) with sodium amalgam afforded the meso- and dl-cyclomers formed by intramolecular cyclization of the diradical (2a). The meso-cyclomer (6a) was thermally converted into the dl-cyclomer (7a), while retroversion of 7a into 6a was achieved photochemically. Reduction of the 4,4′-dimethyl (5b) and 4,4′-di-t-butyl (5c) derivatives of 5a similarly afforded the corresponding meso-(6b and 6c) and dl-(7b and 7c) cyclomers, which can be interconverted to each other. Using NMR spectroscopy to follow the reaction the energies for thermal conversion of meso- to dl- cyclomers were found to be 58.6, 74.5, and 84.5 kJ mol−1 for 6a, 6b, and 6c, respectively. Photodissociation of the cyclomers at −196 °C gave the diradicals (2a–2c), which showed characteristic triplet ESR spectra. The ESR spectra for both 2a and 2b indicated that there were two conformations, each with different zero-field splitting parameters, in 2-methyltetrahydrofuran glass. In contrast, the ESR spectrum of 2c indicated that it has only one conformation. The 4,4′-bis(methoxycarbonyl) derivative (2d) of 2a also forms cyclomers which, upon photolysis, regenerate the diradical. It was concluded that 1,1′-(1,3-propanediyl)bis(pyridinyl) diradicals are substantially in thermal equilibrium with the cyclomers.