Amphiphilic Dipyrrinones

Summary. Replacing the typical lactam β-alkyl substituents of xanthobilirubinic acid and kryptopyrromethenone, two bilirubin analogs long used as model compounds in studies of its photochemistry and metabolism, leads to increased amphiphilicity. Synthesized by base-catalyzed condensation of 3,4-dimethoxypyrrolin-2-one with the appropriate pyrrole α-aldehyde, the 2,3-dimethoxyl analogs of xanthobilirubinic acid and kryptopyrromethenone are yellow-colored dipyrrinones that form intermolecular hydrogen-bonded dimers in the solid, as determined by X-ray crystallography, and in CHCl₃, as revealed by ¹H NMR and vapor pressure osmometry. These two new dipyrrinones are approximately ten times more soluble in water than their parent dipyrrinones.     

Intramolecular Hydrogen-Bonding in a C(10)-Exploded Bilirubinoid

Summary. A new linear tetrapyrrole, with two dipyrrinones connected by a string of 5 carbons, was synthesized from two equivalents of a 9H-dipyrrinone and one of glutaryl dichloride. Unlike typical dipyrrinones, which are intermolecularly hydrogen bonded in the crystal and in CHCl₃ solution, 1,3-bis-[2,3,7,8-tetraethyl-(10H)-dipyrrin-9-carbonyl]propane is a monomer in CHCl₃, as determined by vapor phase osmometry (VPO) measurements. Its crystal structure determination revealed a folded conformation with a novel type of dipyrrinone to dipyrrinone intramolecular hydrogen bonding. Unexpectedly, the same conformation apparently persists in CHCl₃ solution, as shown by ¹H NMR spectroscopy.     

Amphiphilic dipyrrinones: methoxylated [6]-semirubins

Replacing the typical β-alkyl substituents of [6]-semirubin and [6]-oxosemirubin, two intramolecularly hydrogen-bonded bilirubin analogs, with methoxy groups produces amphiphilic dipyrrinones. Synthesized from the respective 9H-dipyrrinones prepared by base-catalyzed condensation of 3,4-dimethoxypyrrolin-2-one with the appropriate pyrrole α-aldehyde, the 2,3-dimethoxy and 2,3,7,8-tetramethoxy analogs of [6]-semirubin are yellow-colored dipyrrinones that form intramolecularly hydrogen-bonded monomers in CDCl₃, as deduced from ¹H NMR NH chemical shifts. They are monomeric in CHCl₃, as determined by vapor pressure osmometry. In contrast, in the solid, X-ray crystallography reveals supramolecular ribbons of intermolecularly hydrogen-bonded (dipyrrinone to dipyrrinone and acid to acid) 2,3,7,8-tetramethoxy-[6]-semirubin. The latter is approximately 20 times more soluble in water than the parent [6]-semirubin with four β-methyl groups.     

Hydrogen-Bonded Dimers in Dipyrrinones and Acyldipyrrinones

Summary.  A crystal structure determination of the 9-acyl-dipyrrinone 9-butanoyl-2,3,7,8-tetramethyl-(10H)-dipyrrin-1-one indicates the presence of intermolecularly hydrogen-bonded dimers; however, in CHCl₃ solution the pigment is monomeric as determined by vapor pressure osmometry measurements. Lacking an alkyl group at C(8), the 9-acyl-dipyrrinone exhibits only a weak tendency to form dimers in CHCl₃ (K _A ∼ 60 M ⁻¹) as determined by analysis of variable temperature ¹H NMR data. In contrast, when the 9-acyl group is replaced by formyl or when the acyl group is fixed in a syn orientation to the pyrrole NH, the dipyrrinone is strongly prone to dimerization in CHCl₃. Received August 22, 2000. Accepted September 5, 2000     

Anion-induced switching of the helical orientation of a chiral indolocarbazole dimer

An indolocarbazole dimer, containing chiral urea appendages, that adopts a helically folded conformation by intramolecular hydrogen bonds as proven by ¹H NMR and circular dichroism (CD) spectroscopy has been prepared. Owing to the preferential formation of one helical conformer, strong CD signals appear in relatively non-polar solvents such as chloroform (CHCl₃) and dichloromethane (CH₂Cl₂) but the signal is negligible in dimethyl sulfoxide (DMSO). In addition, the optical rotation of the dimer is highly sensitive to the polarity of solvents. For example, the magnitude of the specific rotation ([α]_D) is ? 934° in CH₂Cl₂ and ? 657° in CHCl₃ but it is only ? 75° in DMSO. These observations suggest that the dimer folds to a helical structure by intramolecular hydrogen bonds in relatively non-polar solvents but exists in an unfolded extended conformation in polar solvents such as DMSO. The dimer strongly binds anions such as chloride, acetate and sulfate by multiple hydrogen bonds. In addition, anion binding leads to considerable CD spectral changes with the different pattern and degree of Cotton effects depending on the kind of anions. The dimer may be therefore utilised for the construction of an anion-responsive chiroptical sensor or switch.     

Carboxylic acid to amide hydrogen bonding. 10-Oxo-semirubins

Using their amide (and pyrrole) groups, dipyrrinones act as hydrogen bonding receptors for carboxylic acids, as found in a large number of 10-oxo-semirubins (1-6). The latter can be synthesized readily by Friedel-Crafts coupling of 9-H dipyrrinones with half-ester acid chlorides or diacid dichlorides of α,ω-dicarboxylic acids, ranging from C₂ to C₁₀. With ω-oxo-alkanoic acid chains of C₅ or ≥C₅, intramolecular hydrogen bonding is observed. With acid chains <C₅ hydrogen bonding is not observed. Uncharacteristically (for dipyrrinones), 10-oxo-dipyrrinone acids (1-6) and their corresponding esters (1e-6e) remain monomeric in hydrogen bond promoting solvents.     

Converting dipyrrinones to lactim ethers to fluorescent N,N′-difluoroboryl derivatives

A high-yield straightforward conversion of lactams to lactim ethers is shown by the conversion of (10H)-dipyrrin-1-ones to (11H)-dipyrrin-1-ol methyl and ethyl ethers in 90% yield from heating in neat trimethyl or triethyl phosphite at 160°C. Unlike the parent dipyrrinones, which form intermolecularly hydrogen-bonded dimers in CHCl₃, their lactim ethers are shown to be monomeric by vapor pressure osmometry. The latter react with boron trifluoride etherate to N,N′-bridged BF₂ derivatives that exhibit strong fluorescence (φ_F 0.6–0.8) near 535 nm. X-Ray crystal structures were obtained of the lactim ethyl ether of kryptopyrromethenone and the BF₂ derivative of the lactim ethyl ether 2,3-diethyl-7,8-dimethyl-(10H)-dipyrrin-1-one.     

Novel Linear Tetrapyrroles: Hydrogen Bonding in Diacetylenic Bilirubins

Summary. Bilirubin congeners with dipyrrinones conjoined to a diaceteylene unit (–CC–CC–) rather than to –CH₂– were synthesized and examined spectroscopically. This new class of rubrified linear tetrapyrroles cannot easily fold or bend in the middle, but the dipyrrinones can rotate independently about the diacetylene unit. Thus, unlike bilirubin, which is bent in the middle and has a ridge-tile shape, the diacetylene unit orients the attached dipyrrinones along a linear path, and intramolecular hydrogen bonding between the dipyrrinones and opposing carboxylic acids preserves a twisted linear molecular shape when the usual propionic acids are replaced by hexanoic. In a bis-hexanoic acid rubin, the extended planes of the dipyrrinones intersect along the –(CC)₂– axis at an angle of 102° for the conformation stabilized by intramolecular hydrogen bonding. With propionic acid chains, however, neither CO₂H can engage an opposing dipyrrinone in intramolecular hydrogen bonding, and the energy-minimum conformation of this linear pigment, shows nearly co-planar dipyrrinones, with an intersection of an angle of 180° of the extended planes of the dipyrrinones. Spectroscopic evidence for such linearized and twisted (bis-hexanoic) and planar (bis-propionic) structures comes from the pigments NMR spectral data and their exciton UV-Vis and induced circular dichroism spectra.     

Converting dipyrrinones to lactim ethers to fluorescent <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>′-difluoroboryl derivatives

A high-yield straightforward conversion of lactams to lactim ethers is shown by the conversion of (10H)-dipyrrin-1-ones to (11H)-dipyrrin-1-ol methyl and ethyl ethers in 90% yield from heating in neat trimethyl or triethyl phosphite at 160°C. Unlike the parent dipyrrinones, which form intermolecularly hydrogen-bonded dimers in CHCl₃, their lactim ethers are shown to be monomeric by vapor pressure osmometry. The latter react with boron trifluoride etherate to N,N′-bridged BF₂ derivatives that exhibit strong fluorescence (φ_F 0.6–0.8) near 535 nm. X-Ray crystal structures were obtained of the lactim ethyl ether of kryptopyrromethenone and the BF₂ derivative of the lactim ethyl ether 2,3-diethyl-7,8-dimethyl-(10H)-dipyrrin-1-one. Correspondence: David A. Lightner, Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020 USA.     

Intermolecularly Hydrogen-Bonded Dimeric Helices. Tripyrrindiones

A rare and unusual class of tripyrrolic compounds, violet-colored tripyrrin-1,14-diones, can be prepared easily and in moderately high yields from base (piperidine)-catalyzed condensation of 3-pyrrolin-2-ones with 2,5-diformylpyrroles. Dipyrrinones adopt the all-syn-Z conformation leading to helical, lock-washer like structures, which form dimers that are held together by intermolecular hydrogen bonds in nonpolar solvents and in the crystal. Strong bathochromic spectral shifts of the tripyrrindione ∼480 nm long wavelength UV-visible absorption band are seen with added base: DBU, 615 nm; TFA, 573 nm; and Zn(OAc)₂, 586 nm.     

Reactions of transition metal carbonyl anions with 2-(1-bromoalkylidene)thiazolidin-4-ones: halogenophilic attack or deprotonation

Bromophilic attack by the transition metal carbonyl anion, [Re(CO)₅]Na (pK_a = 21.1), on 2-(1-bromoalkylidene)thiazolidin-4-ones is significantly faster than abstraction of an acidic lactam hydrogen (pK_a ∼17-18), when the generated carbanion is stabilized by an α-CN or α-PhCO group. The bromophilic reaction of 2-(1-bromoalkylidene)thiazolidin-4-one, having an α-CN electron-withdrawing group, resulted in formation of a new metallacyclic anionic complex. With less reactive vinyl bromides, containing an α-CONHPh or α-CO₂Et group, only deprotonation is observed. The role of the metal carbonyl anion is highlighted by a comparison with the 9-methylfluorenide carbanion (pK_a of 9-methylfluorene is 22.3), which reacts exclusively via a deprotonation pathway.     

Chiral calix[4]azacrowns for enantiomeric recognition of amino acid derivatives

In this study the synthesis of novel chiral calix[4]azacrown derivatives has been reported. The enantioselectivity of chiral receptors was investigated by using UV-vis spectroscopy. All the chiral calix[4]arene derivatives exhibited certain chiral recognition toward the enantiomers of phenylalanine (Phe-OMe·HCl) and alanine methyl ester hydrochlorides (Ala-OMe·HCl). As a chiral receptor, the furfuryl-armed calix[4]azacrown ether 7 has the best enantiomeric discriminating ability for α-amino acid ester hydrochlorides (up to K_L/K_D=2.08, ΔΔG₀=−1.82 kJ mol⁻¹) in CHCl₃. The enantiomeric recognition abilities for guests are also discussed from a thermodynamic point of view.     

Development of negligible depletion hollow fiber membrane-protected liquid-phase microextraction for simultaneous determination of partitioning coefficients and acid dissociation constants

A new method based on negligible depletion hollow fiber-protected liquid-phase microextraction coupled with high-performance liquid chromatography (HPLC) was developed for the simultaneous determination of partitioning coefficients (K_OW) and acid dissociation constants (pK_a), by using phenol, 4-chlorophenol and 2,4-dichlorophenol as model compounds. A 37-mm length polypropylene hollow fiber membranes (600 μm inner diameter, 200 μm wall-thickness, 0.2 μm pore size, ∼70% porosity) with two-end sealed were filled with 1-octanol by ultrasonic agitation to prepare the extraction device. The extraction device was deployed in sample solutions, prepared by spiking target analytes in 1-octanol saturated aqueous solutions (500 mL), for negligible depletion extraction. After equilibrium was reached (∼5 h), the 1-octanol in the lumen of the hollow fiber membrane was collected for HPLC determination of the target analytes. As the depletion of the analytes in aqueous samples was negligible, the distribution coefficient (D_OW) could be calculated based on the measured equilibrium concentration in 1-octanol (C_O) and the initial concentration (C_W) in the aqueous sample of the target analyte (D_OW = C_O/C_W). The D_OW values measured at various pH values were nonlinearly regressed with pH to obtain the K_OW and pK_a values of a compound. Results showed that the measured values of the K_OW and pK_a of these model compounds agreed well with literature data.     

Synthesis and examination of amine-cyanocarboxyboranes, the boron analogues of α-cyanocarboxylic acids: X-ray structural study of the first lactam containing a boron atom in the lactam ring

The first representatives of chiral boron atom-containing amine-cyanomethoxycarbonyl boranes (A · BH(CN)COOMe) have been synthesized either from the corresponding amine-bromocyanomethoxycarbonylborane complexes with [Bu₄N]CN or from Me₃N · BH(CN)COOMe and an amine in a base-exchange reaction. Acid hydrolyses of methyl esters generated the free acids (A · BH(CN)COOH), which are isoelectronic to the α-cyano carboxylic acids. Their pK_a values and hydrolysis half-lives in acidic medium (that is rate of proton reduction) have been determined. Similarly to the alpha cyano carboxylic acids, the cyano group attached to the boron (in alpha position to the COOH group) increased the acid strength of carboxy boranes with 2.0-2.5 orders of magnitude. Independently from the type of the amine, pK_a values of the amine-cyanocarboxyboranes (6.34-5.82) decrease consistently with the increase of pK_b values of the amines. Hydrolytic decomposition rate of the alkylamine complexes increases with increasing pK_b values of the amines while the opposite was found for pyridine base complexes. When considering both types of the amines, hydrolysis half-lives of the complexes range over several orders of magnitude from 0.005 to 400 h. Based on these observations protonation of the amine nitrogen atom appears to be the rate determining step in the hydrolysis process. With loss of methanol, 2-NH₂-py · BH(CN)COOMe transformed into a five membered lactam derivative. X-ray diffraction revealed that the pyridine ring is coplanar with the five membered lactam ring. In the crystal two molecules are connected in a head to tail arrangement by strong intermolecular H-bonds between N(2)-H and the carbonyl oxygen (O1) with a donor and acceptor distance of 2.867(3) Å. Three new cyanomethoxycarbonylborates having the composition of K[BH_n(CN)_3−nCOOMe] (n = 1, 2) and K[B(OH)(CN)₂COOMe] have also been synthesized and their properties examined.     

Molecular recognition of polymethoxybenzenes by host molecule comprised of two pyromellitic diimides and two dialkoxynaphthalenes

For the continuing study of the molecular recognition of the π-electron-poor host comprised of two pyromellitic diimides and two dialkoxynaphthalenes, its inclusion with π-electron-rich polymethoxybenzenes has been examined. The UV-vis titration studies indicated following order of the association constants (K_a's) as 1:1 complexes in CHCl₃: 1,3,5-trimethoxybenzene (31.3 M⁻¹)>1,3-dimethoxybenzene (9.2 M⁻¹)>1,2-dimethoxybenzene (6.5 M⁻¹)>1,4-dimethoxybenzenes (2.8 M⁻¹). The X-ray structural analysis of the complexes between the host and dimethoxybenzenes proved the intracavity 1:1 complexes and provided useful information on the structures of the complexes. Not only charge transfer interactions but also other weak interactions such as electrostatic, van der Waals, and the unique hydrogen bonds between the α-hydrogen atoms of the naphthalene and the methoxy oxygen atoms were considered to be responsible for the magnitude of the K_a's. Thus molecular recognition of polymethoxybenzenes has been accomplished by the neutral host using multipoint weak interactions in an organic solvent.     

Peripheral and non-peripheral-designed multifunctional phthalocyanines; synthesis, electrochemistry, spectroelectrochemistry and metal ion binding studies

A novel type of ionophore ligands, 3′-(2,3-dihydroxypropylthio)-phthalonitrile and 4′(2,3-dihydroxypropylthio)-phthalonitrile, and their α- and β-tetrasubstituted metallo phthalocyanines, (MPc), (M = Zn^II, Co^II, Mn^IIICl, Fe^IIIAc, Cu^II) have been prepared and fully characterized by elemental analysis, FT-IR, ¹H and ¹³C NMR, and MS (ESI and Maldi-TOF). The complexes are soluble in both polar and non-polar solvents, such as MeOH and EtOH, THF, CHCl₃ and CH₂Cl₂. The spectroscopic properties of the complexes are affected strongly by the electron-donating sulfanyl units on the periphery of the phthalocyanines. The cation binding properties of the complexes, for example using Ag^I and Pd^II, were evaluated by UV-Vis spectroscopy and the results show the formation of polynuclear phthalocyanine complexes. Functional donors on the periphery of the zinc and copper complexes coordinate to Ag^I and Pd^II to give ca. a 2:1 metal-phthalocyanine complex binding ratio for the concentration of 2.5 × 10⁻⁵ M (Pc) and 1.0 × 10⁻³ M (Metal ions). Voltammetric and in-situ spectroelectrochemical studies were performed to characterize the redox behavior of the complexes. An in-situ electrocolorimetric method was applied to investigate the colors of the electro-generated anionic and cationic forms of the complexes.     

Kinetic study of the oxidative addition reaction between methyl iodide and [Rh(FcCOCHCOCF3)(CO)(PPh3)]: Structure of [Rh(FcCOCHCOCF3)(CO)(PPh3)(CH3)(I)]

The kinetics of oxidative addition of CH₃I to [Rh(FcCOCHCOCF₃)(CO)(PPh₃)], where Fc = ferrocenyl and (FcCOCHCOCF₃)⁻ = fctfa = ferrocenoylacetonato, have been studied utilizing UV/Vis, IR, ¹H and ³¹P NMR techniques. Three definite sets of reactions involving isomers of at least two distinctly different classes of Rh^III-alkyl and two different classes of Rh^III-acyl species were observed. Rate constants for this reaction in CHCl₃ at 25 °C, applicable to the reaction sequence below, were determined as k₁ = 0.00611(1) dm³ mol⁻¹ s⁻¹, k₋₁ = 0.0005(1) s⁻¹, k₃ = 0.00017(2) s⁻¹ and k₄ = 0.0000044(1) s⁻¹ while k₋₃ ? k₃ and k₋₄ ? k₄ but both ≠0. The indeterminable equilibrium K₂ was fast enough to be maintained during Rh^I depletion in the first set of reactions and during the Rh^IIIalkyl2 formation in the second set of reactions. From a ¹H and ³¹P NMR study in CDCl₃, K_c1 was found to be 0.68, K_c2 = 2.57, K_c3 = 1.00, K_c4 = 4.56 and K_c5 = 1.65.     

Soluble and processable conjugated polyazines with oligo(p-phenylene vinylene)s

An efficient polycondensation reaction between α,ω-diformyl functional aromatics, namely 2,5-diheptyloxy-1,4-diformylbenzene and side-chain substituted α,ω-diformyl oligo(p-phenylene vinylene) (OPV) with hydrazine afforded novel soluble and processable conjugated polymers, P1 and P2, respectively. The reaction conditions were investigated and structural analysis of the polymers was carried out by means of ¹H, ¹³C, ¹⁵N NMR, indicating all-trans configured CN-NC linkages. The molecular weights M_n were observed at ∼1100-1400 g/mol for P1 and ∼8700-10,500 g/mol for P2. The optical properties showed absorption maxima at ∼455 nm and ∼487 nm for P1 and P2 (CHCl₃ solutions), respectively, red shifted by 31-60 nm relative to the monomer aromatics due to conjugation through the azine linkage. The emission maxima are observed at ∼515 nm and ∼560 nm for P1 and P2 (CHCl₃ solutions), respectively. Thin films of P2 readily undergo n-doping.     

Synthesis of reactive [Al(Et)(q′)2] (q′ = 2-methyl-8-quinolinolato) serving as a precursor of light emitting aluminum complexes: Reactivity, optical properties, and fluxional behavior of the aluminum complexes

Reaction of AlEt₃ with 2-methyl-8-quinolinol gave ethylbis(2-methyl-8-quinolinolato)aluminum complex [Al(Et)(q′)₂] 1. The complex 1 provided photoluminescent Al complexes by reactions with phenols, carboxylic acid, and H₂O. The α-CH₂ hydrogens in the Et group of 1 was diastereotropic as revealed by ¹H NMR spectroscopy because of the presence of a chiral center at Al. The chirality at Al was dynamically lost at elevated temperature in CDCl₂CDCl₂ and DMSO-d₆, as indicated by temperature dependent ¹H NMR spectroscopy. This dynamic or fluxional behavior of 1 is explained by rotation of the 2-methyl-8-quinolinolato ligand. The kinetic parameters of the dynamic process were estimated at ΔH^‡ = 135 kJ mol⁻¹ and ΔS^‡ = 159 J K⁻¹ mol⁻¹ in CDCl₂CDCl₂ and at ΔH^‡ = 124 kJ mol⁻¹ and ΔS^‡ = 151 J K⁻¹ mol⁻¹ in DMSO-d₆, respectively, at 350 K. Structures of some of the obtained Al complexes were confirmed by single-crystal X-ray crystallography. These Al complexes showed photoluminescence peaks at 492-507 nm in CHCl₃ with quantum yields of 7-23%.     

Solid triphenylmethanol: A molecular material that undergoes multiple internal reorientational processes on different timescales

In solid triphenylmethanol, the molecules are arranged in hydrogen-bonded tetramers, and it is already well established that the hydrogen bonding in this material undergoes a dynamic switching process between different hydrogen bonding arrangements. In addition to this motion, we show here, from solid-state ²H NMR studies of the deuterated material (C₆D₅)₃COH, that each phenyl ring in this material undergoes a 180°-jump reorientation about the C₆D₅-C(OH) bond, with an activation energy of ca. 50 kJ mol⁻¹. The timescale for the phenyl ring dynamics is several orders of magnitude longer than the timescale for the hydrogen bond dynamics in this material, and is uncorrelated with the dynamics of the hydrogen bonding arrangement.