Strongly fluorescent dipyrrinones. Internal quenching

Yellow N,N′-carbonyl-bridged dipyrrinones can generally be prepared from dipyrrinones simply by reaction with N,N′-carbonyldiimidazole in the presence of a strong, non-nucleophilic base. They are typically intensely fluorescent, with fluorescent quantum yields approaching 1.0. In an effort to shift the excitation wavelength, and thus the fluorescence emissions, strongly to the red, we prepared bridged dipyrrinones conjugated with thiobarbituric acid and Meldrum’s acid substituents at C-9. Such conjugation causes the dipyrrinones to have a magenta color (absorption wavelength shifted from ∼400 nm of a typical dipyrrinone to ∼550 nm of the dipyrrinone conjugate). For comparison, we also prepared analogs with formyl, carboxyl, acrylate, and acetyl substituents at C-9. Unexpectedly and uniquely, the 9-CHO substituent caused the fluorescence quantum yield to drop to ∼10⁻³ while carboethoxy substituent exerted only a minor influence.     

Methoxyl-induced fluorescence quenching in N,N′-bridged 9H-dipyrrinones and an X-ray crystal structure

Strongly fluorescent dipyrrinones can be prepared by bridging the pyrrole and lactam nitrogens with a carbonyl group, from reaction with N,N′-carbonyldiimidazole in the presence of a strong, non-nucleophilic base. The yellow, N,N′-carbonyl-bridged dipyrrinones typically have fluorescent quantum yields (φ_F) approaching 1.0. Thus, in chloroform, N,N′-bridged 9H-dipyrrinones with β-alkyl substituents: 2,3-diethyl-7,8-dimethyl has φ_F = 0.90 (λ_em = 465 nm) and 2,3-dimethyl-7,8-dimethoxy has φ_F = 0.84 (λ_em = 482 nm). In contrast, 2,3-dimethoxy-7,8-dimethyl and 2,3,7,8-tetramethoxy show red-shifted λ_em but with strongly reduced φ_F: φ_F = 0.10 (λ_em = 511 nm) and 0.08 (λ_em = 511 nm), respectively. Methoxy substituents on the lactam, but not the pyrrole ring act to quench the fluorescence and shift the emission and excitation wavelengths bathochromically. The first X-ray crystal structure of an N,N′-carbonyl-bridged dipyrrinone was obtained from 7,8-dimethoxy-2,3-dimethyl-10H-dipyrrin-1-one. Correspondence: David A. Lightner, Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020, USA.     

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.     

Fluorescence detected circular dichroism of a red-shifted exciton-coupling chromophore <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>′-carbonyl-bridged dipyrrinone derivative using an ellipsoidal device

A fluorescent red-shifted exciton-coupling chromophore, N,N′-carbonyl-bridged dipyrrinone, was subjected to fluorescence-detected CD (FDCD) measurements as a primitive structure-elucidating probe with trans-1,2-cyclohexanediol template in several solvents under various instrumental conditions. With the help of a JASCO ellipsoidal mirror device FDCD465, a chloroform solution achieved the sensitivity enhancement by 50 times of the transmission CD and 5 times of the conventional FDCD. All FDCD spectra were completely free from the polarization artifacts. Correspondence: Tatsuo Nehira and David A. Lightner, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-hiroshima 739-8521, Japan; Department of Chemistry, University of Nevada, Reno, Nevada 89557, USA.     

Converting 9-Methyldipyrrinones to 9-H and 9-CHO Dipyrrinones

Yellow 9-methyldipyrrinones can be converted readily and in high yields to symmetric linear tetrapyrroles, blue biliverdinoids, which are cleaved in half, smoothly at room temperature to afford yellow 9-H dipyrrinones, and 9-CHO dipyrrinones as their violet to orange colored adducts with the carbon acid used for the scission: thiobarbituric acid (TBA), N,N′-diethylthiobarbituric acid, barbituric acid, N,N′-dimethylbarbituric acid, and Meldrum's acid. The adducts, usually only of passing interest, are formally Knövenagel condensation products of a 9-CHO dipyrrinone with TBA and other carbon acids of this work, and a reverse Knövenagel reaction of such adducts leads to 9-CHO dipyrrinones. Under a set of improved reaction conditions the sequence thus efficiently converts 9-CH₃ dipyrrinones to 9-H and 9-CHO dipyrrinones.     

Pyrrole β-amides: Synthesis and characterization of a dipyrrinone carboxylic acid and an N-Confused fluorescent dipyrrinone

Pyrrole β-amides are useful building blocks for the preparation of novel molecular architectures that can be used in supramolecular chemistry and sensor development. Under basic conditions, pyrrole β-amides with an α-aldehyde produce different condensation products when reacted with pyrrolinones depending on the amide substitution. Secondary amides form the expected dipyrrinones, but unexpectedly undergo a subsequent trans-amidation with the pyrrolinone nitrogen to produce an unsymmetrical imide (an N-confused fluorescent dipyrrinone). Under the same conditions, tertiary amides produce the expected dipyrrinone carboxylic acids, which have been shown to have strong self-association properties as determined by vapor pressure osmometry measurements, NMR studies, and X-ray crystal structure determination. Furthermore, an N-confused fluorescent dipyrrinone was produced from the same trans-amidation reaction during attempts to decarboxylate a dipyrrinone amide with a 9-carboxylic moiety.     

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.     

Strongly fluorescent dipyrrinones—substituent effects

Bright yellow N,N'‐carbonyl‐bridged dipyrrinones (substituted 3H,5H‐dipyrrolo[1,2‐c:2′,1′‐f]pyrimidine‐3,5‐diones) were synthesized by reaction of the parent dipyrrinone with carbonyldiimidazole. Their solutions in organic solvents fluoresced strongly, with fluorescent quantum yields (?_F)0.32‐0.92.     

Fluorescence detected circular dichroism of a red-shifted exciton-coupling chromophore N,N′-carbonyl-bridged dipyrrinone derivative using an ellipsoidal device

A fluorescent red-shifted exciton-coupling chromophore, N,N′-carbonyl-bridged dipyrrinone, was subjected to fluorescence-detected CD (FDCD) measurements as a primitive structure-elucidating probe with trans-1,2-cyclohexanediol template in several solvents under various instrumental conditions. With the help of a JASCO ellipsoidal mirror device FDCD465, a chloroform solution achieved the sensitivity enhancement by 50 times of the transmission CD and 5 times of the conventional FDCD. All FDCD spectra were completely free from the polarization artifacts.     

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     

Crystal Structure and Conformation of a 10-Thiabilirubin

 A crystal structure determination of a bilirubin analog with a sulfur instead of a C(10)–CH₂ linking the two dipyrrinones is reported. Conformation-determining torsion angles and key hydrogen bond distances and angles are compared to those obtained from molecular dynamics calculations as well as to the corresponding data from X-ray determinations and molecular dynamics calculations of bilirubin. Like other bilirubins, the component dipyrrinones of the analog are present in the bis-lactam form with (Z)-configurated double bonds at C(4) and C(15). Despite the large differences in bond lengths and angles at –S–vs.–CH₂–, the crystal structure shows considerable similarity to bilirubin: both pigments adopt a folded, intramolecularly hydrogen-bonded ridge-tile conformation stabilized by six hydrogen bonds – although the interplanar angle of the ridge-tile conformation of the title compound is smaller (∼ 86°) than that of bilirubin (∼ 98°). The collective data indicate that even with long C–S bond lengths and a smaller C–S–C bond angle at the pivot point on the ridge-tile seam, intramolecular hydrogen bonding persists.     

High optical transparency and low dielectric constant of novel organosoluble poly(ether ketone amide)s derived from an unsymmetrical diamine containing trifluoromethyl and methyl pendant groups

A series of novel fluorinated poly(ether ketone amide)s (PEKAs) were prepared from an unsymmetrical aromatic diamine, (4′-(4″-amino-2″-trifluoromethylphenoxy)-3′,5′-dimethylphenyl)(4-aminophenyl)-methanone (1), with various aromatic dicarboxylic acids using the phosphorylation polycondensation technique. The PEKAs had inherent viscosities ranging from 0.43 to 0.65 dl/g. All the fluorinated PEKAs could be soluble in many polar organic solvents such as N-methyl-2-pyrrolidinone (NMP), N,N′-dimethylacetamide (DMAc), N,N′-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and tetrahydrofuran (THF). Flexible and tough polymer films could be prepared by casting from DMAc solvent. The PEKA films exhibited high optical transparency with a cutoff wavelength of 354–365 nm and good mechanical properties with tensile strengths of 78–98 MPa and elongations at break of 11.5–18.5%. They showed glass-transition temperatures in the range of 288−323 °C and the onset decomposition temperatures in the range of 450−461 °C in nitrogen atmosphere. Meanwhile, the PEKA films possessed low dielectric constants of 1.98–2.71 at 1 MHz and low moisture absorption (<2%). Due to their properties, the fluorinated PEKAs could be considered as photoelectric and microelectronic materials.     

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.     

Spectral and fluorescent properties of cross-conjugated polyene ketones with terminalN-methylpyrrole residues

The spectral and fluorescent properties of a number of cross-conjugated ketones with one or two terminalN-methylpyrrole residues and those of polyene bis-ω, ω′-dimethylamino ketones with methyl substituents in the polyene chain and of some related compounds were studied. The photophysical properties of cross-conjugated ketones with terminalN-methylpyrrole residues are similar to those of the corresponding polyene bis-ω, ω′-dimethylamino ketones studied in detail previously. In both series of compounds, the absorption and fluorescence spectra undergo a bathochromic shift following an increase in the length of the polyene chains or introduction of α,α′-trimethylene or α,α′-dimethylene bridges into these chains; the same trend is observed on passing from less polar solvents to more polar solvents (positive solvatochromism). Thermochromism (long-wavelength shift of the absorption spectra upon cooling the solutions) is observed in both series of compounds. The introduction of methyl substituents into the polyene chains of bis-ω,ω′-dimethylamino ketones results in a decrease in the fluorescence quantum yield. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1293–1298, July, 1999.     

Crystal Structure and Conformation of a 10-Thiabilirubin

Summary.  A crystal structure determination of a bilirubin analog with a sulfur instead of a C(10)–CH₂ linking the two dipyrrinones is reported. Conformation-determining torsion angles and key hydrogen bond distances and angles are compared to those obtained from molecular dynamics calculations as well as to the corresponding data from X-ray determinations and molecular dynamics calculations of bilirubin. Like other bilirubins, the component dipyrrinones of the analog are present in the bis-lactam form with (Z)-configurated double bonds at C(4) and C(15). Despite the large differences in bond lengths and angles at –S–vs.–CH₂–, the crystal structure shows considerable similarity to bilirubin: both pigments adopt a folded, intramolecularly hydrogen-bonded ridge-tile conformation stabilized by six hydrogen bonds – although the interplanar angle of the ridge-tile conformation of the title compound is smaller (∼ 86°) than that of bilirubin (∼ 98°). The collective data indicate that even with long C–S bond lengths and a smaller C–S–C bond angle at the pivot point on the ridge-tile seam, intramolecular hydrogen bonding persists. Received August 16, 2001. Accepted September 12, 2001     

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.     

Fluorescent polyacrylamide nanoparticles for naproxen recognition

We present the synthesis of fluorescent acrylamide nanoparticles (FANs) capable of recognizing non-steroidal anti-inflammatory drugs (NSAIDs) in buffered aqueous solutions. Within this important group, we selected naproxen, one of the 2-arylpropionic acids (profens), due to its use for the treatment of moderate pain, fever, and inflammation. The nanosensors were prepared under mild conditions of inverse microemulsion polymerization using aqueous acrylamide as the monomer and N,N′-methylenebisacrylamide as the cross-linker, employing the surfactants polyoxyethylene-4-lauryl ether (Brij?30) and sodium bis(2-ethylhexyl)sulfosuccinate in hexane. Furthermore, a fluorescent monomer, (E)-4-[4-(dimethylamino)styryl]-1-[4-(methacryloyloxymethyl)benzyl]pyridinium chloride (mDMASP) has been synthesized and incorporated into the nanoparticles. The nanosensors exhibit a broad absorbance at around 460 nm and a structureless fluorescence band with maximum at 590 nm in 0.5 M phosphate buffer (pH = 7.2). The recognition process is performed on the basis of ionic interactions which are monitored by the fluorescence increase at 590 nm upon addition of different concentrations of naproxen. The FANs show a size distribution in the range of 20–80 nm, with a hydrodynamic diameter of 34 nm. In order to assess the selectivity of the FANs, a systematic study was conducted on the effect produced by drugs and biomolecules that could interfere with the analysis of naproxen.     

Exciton Chirality. (A) Origins of and (B) Applications from Strongly Fluorescent Dipyrrinone Chromophores

(A) The origin of exciton interaction and examples of its application to organic stereochemistry are presented. (B) N,N-Carbonyl-bridged dipyrrinones constitute a new class of highly fluorescent chromophores suitable for investigations of stereochemistry and absolute configuration. N,N-Carbonylxanthobilirubic acid esters are strongly fluorescent, with a fluorescence quantum yield (_F) 0.8, but produce only weak exciton CD from the trans-1,2-cyclohexanediol template. The ester of an analog with benzoic acid replacing propionic, N,N-carbonyl-8-(4-carboxyphenyl)-3-ethyl-2,7,9-trimethyl-(10H)-dipyrrin-1-one, exhibits strong fluorescence (_F=0.68, _em=493nm, _ex=422nm in CHCl₃) and UV-Vis absorption (21000 at 424nm) in organic solvents. Its diester with (1S,2S)-cyclohexanediol is fluorescent and exhibits exciton circular dichroism (=+15dm³·mol^–1·cm^–1, =432nm; =–4dm³·mol^–1cm^–1, =380nm) that correlates with the Exciton Chirality Rule.     

Syntheses and properties of poly (amide–imide)s based on 5,5′-bis[4-(4-trimellitimidophenoxy)phenyl]-hexahydro-4,7-methanoindan and aromatic diamines

 A novel polymer-forming diimide–diacid, 5,5′-bis[4-(4-trimellitimido phenoxy)phenyl]-hexahydro-4,7-methanoindan (II), was prepared by the condensation reaction of 5,5′-bis[4-(4-aminophenoxy)phenyl]-hexahydro-4,7-methanoindan with trimellitic anhydride. A series of novel aromatic poly(amide–imide)s (PAIs) containing polycyclic cardo groups was prepared by the direct polycondensation of II with various aromatic diamines using phosphorylation techniques. The polymers had inherent viscosities between 0.71 and 0.96 dl/g. The polymers were soluble in polar solvents such as N-methyl-2-pyrrolidone, N,N-dimethylacetamide (DMAc) and N,N-dimethylformamide, and could be cast from their DMAc solutions into transparent, flexible, and tough films, except for III _a . These films had yield strengths of 85–114 MPa, tensile strengths of 77–102 MPa, an elongation at break of 8–17%, and initial moduli of 2.0–2.7 GPa. Wide-angle X-ray diffraction revealed that the polymers are amorphous. The glass-transition temperatures of the polymers were in the range 242–312 °C. All the PAIs exhibited no appreciable decomposition below 430 °C, and their 10%-weight-loss temperatures were in the range 484–507 °C in nitrogen and 494–515 °C in air. Received: 26 January 1999 Accepted in revised form: 11 May 1999     

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.