Crowned Macrocycles Containing Two Pyrrolo[1,2-a] Indoles Created By Intramolecular Fusion

Heterocyclic fused-ring systems are of utmost importance because of their presence in many natural products with biological activity. Pyrroloindoles are tricyclic heterocycles that are present in various bioactive and medicinally valuable compounds. Herein, we report the synthesis of phenylene-bridged bis-pyrrolo[1,2-a]indole crowned macrocycles 1 – 3 in which the pyrrolo[1,2-a]indole moieties were formed via intramolecular fusion. The macrocycles were thoroughly characterized by 1D and 2D NMR, HRMS and X-ray crystallographic studies. The X-ray structure revealed that the two pyrrolo[1,2-a]indole moieties were parallel to each other, and one pyrrolo[1,2-a]indole unit was deviated by an angle of 9.54° while the other pyrrolo[1,2-a]indole unit was deviated by an angle of 12.0° from the mean plane defined by 28 core atoms. The macrocycles 1 – 3 absorb in the visible region and readily undergo oxidations because of their electron rich nature. The macrocycles 1 – 3 upon treatment with trifluoroacetic acid (TFA) generates the corresponding cation radicals 1 – 3 ^.+ which were stable in the open air for a week. The cation radicals 1 – 3 ^.+ absorb strongly in the NIR region and the experimental observations on crowned macrocycles 1 – 3 were corroborated by DFT and TD-DFT studies.     

Synthesis and properties of BF2- & PO2-complexes of mono meso-heterocycle substituted 25-oxasmaragdyrins and derivatives

BF₂- and PO₂-smaragdyrins containing one five membered heterocycle such as pyrrole, thiophene and furan at one of the meso-position of corresponding 25-oxasmaragdyrins were synthesized by treating the appropriate mono meso-heterocycle substituted 25-oxasmaragdyrin with BF₃.OEt₂ and POCl₃ respectively in CH₂Cl₂ under mild reaction conditions. All macrocycles were thoroughly characterized by HR-MS and 1D and 2D NMR spectroscopy. The presence of a five membered heterocycle in place of a six membered aryl group significantly alters the electronic properties of the smaragdyrin macrocycle as reflected in their spectral and electrochemical properties. The meso-pyrrole BF₂-smaragdyrin was subjected to a Vilsmeier-Haack reaction to prepare meso-(α-formyl pyrrolyl) BF₂-smaragdyrin which was subsequently used to prepare meso-(α-dipyrromethanyl pyrrolyl) BF₂-smaragdyrin. The further use of meso-heterocycle substituted BF₂- and PO₂-oxasmaragdyrins was demonstrated by treating meso-pyrrolyl BF₂-smaragdyrin with pentafluorobenzaldehyde in CHCl₃ under mild acid catalysed conditions to afford an unusual dipyrromethanyl bridged BF₂-smaragdyrin dyad which exhibits excellent photophysical properties.     

6 + 6 Macrocycles derived from 2,6-diformylpyridine and trans-1,2-diaminocyclohexane

While the non-templated reaction of racemic trans-1,2-diaminocyclohexane with 2,6-diformylpyridine leads to a mixture of 2?+?2 and 4?+?4 macrocyclic imines, the reaction of the isolated 2?+?2 macrocycle with cadmium(II) chloride results in the fusion of three smaller macrocyclic units into a large 6?+?6 macrocycle. The X-ray molecular structures of the hexanuclear cadmium complex of this macrocycle as well as the derived 6?+?6 protonated amine reveal multiply folded macrocycles that adopt container-type conformations.     

Halide Anion Mediated Dimerization of a meso‐Unsubstituted N‐Confused Porphyrin

The new N‐confused porphyrin (NCP) derivatives, meso‐unsubstituted β‐alkyl‐3‐oxo N‐confused porphyrin (3‐oxo‐NCP) and related macrocycles, were synthesized from appropriate pyrrolic precursors by a [3+1]‐type condensation reaction. 3‐Oxo‐NCP forms a self‐assembled dimer in dichloromethane that is stabilized by complementary hydrogen‐bonding interactions arising from the peripheral amide‐like moieties. The protonated form of 3‐oxo‐NCP was observed to bind halide anions (F^?, Cl^?) through the outer NH and the inner pyrrolic NH groups, thus affording a dimer in dichloromethane. The structure of the chloride‐bridged dimer in the solid state was determined by X‐ray diffraction analysis.     

Highly substituted 2,3,7,8,12,13,17,18-octaethylporphyrins with meso aryl residues

Highly substituted porphyrin-bearing meso aryl groups are useful compounds for optical applications and for studies on the interrelationship between the substituent pattern, macrocycle conformation and physical properties. They serve as biomimetic models for the function of tetrapyrroles in nature and help to elucidate modulation of cofactor properties through conformational effects. Using a sequence of lithium organic substitution reactions the synthesis of novel free base 5,10-A₂- and 5,10-AB-2,3,7,8,12,13,17,18-octaethylporphyrins bearing donating groups such as -OMe and -NMe₂ on the aryl-substituent was achieved. Larger aromatic residues (1-naphthyl, 9-anthracenyl and 9-phenanthrenyl) could be introduced into the macrocycle system as well, and these systems were used for the preparation of highly substituted porphyrins with a mixed substituent pattern. Using phenanthrenyl derivatives, the complete series of meso phenanthrenyl substituted octaethylporphyrins was successfully synthesized and the palladium complexes were prepared for photophysical investigations. Structural studies clearly showed the influence of individual substituents on the conformation of the tetrapyrrole macrocycle and conformational analyses revealed the variation of the underlying distortion modes depending on the type and arrangement of the meso substituents.     

A new hexaaminomacrocycle for ditopic binding of bromide

A hexaaminomacrocycle L, containing four secondary and two tertiary amines has been synthesized and crystallized with hydrobromic acid. The structural analysis of the bromide complex suggests that the ligand in its tetraprotonated form, is involved in coordinating two bromides from both the sides via hydrogen bonding interactions with N?Br⁻ distance of 3.351 Å, forming a ditopic complex. The other two bromides are outside the cavity, and singly bonded to the macrocycle. The molecules are packed showing layer structures in which the internal bromides are locked between the layers of macrocycles. The bromide anions are coordinated alternatively by one and two hydrogen bonds with the protonated amines from the two adjacent macrocycles.     

A facial microwave-assisted synthesis, spectroscopic characterization and preliminary complexation studies of calix[4]pyrroles containing the hydroxamic-acid moiety

The synthesis, spectroscopic characterization and preliminary complexation properties of functionalized calix[4]pyrroles are described. To date, two generalized preparative approaches have been pursued (i) modifying the basic pyrrole-plus-ketone synthesis of calix[4]pyrrole by using microwave irradiation protocol, (ii) the basic meso-tetra(methyl) meso-tetra(p-nitrophenyl) calix[4]pyrrole skeleton was functionalized to give hydroxamic acids, especially in the meso-position of the macrocycles. The structures of novel calix[4]pyrrole hydroxamic acid derivatives were confirmed on the basis of various physico-chemical techniques such as elemental analysis, FT-IR, ¹H NMR and FAB-Mass. The results of preliminary studies on the extraction of vanadium (V) with the host calix[4]pyrrole hydroxamic acids were elucidated by significant examination of UV–Vis spectroscopy and ICP-AES. Single crystal structure of basic meso-tetra(methyl) meso-tetra (p-nitro phenyl) calix[4]pyrrole moiety has also been reported.     

Phenylene‐Bridged Core‐Modified Planar Aromatic Octaphyrin: Aromaticity,Photophysical and Anion Receptor Properties

The synthesis of a planar expanded meso porphyrin with an intramolecular para‐phenylene‐bridged core is reported. The planarity of the octaphyrin macrocycle was confirmed by single‐crystal X‐ray structural analysis, in which the bridged para‐phenylene unit deviated by 27° from the mean macrocyclic plane. Spectroscopic analyses and theoretical calculations suggested that the macrocycle was Hückel aromatic and followed a major [34 π] single‐conjugation pathway, which indicated that the bridging para‐phenylene unit was not involved in the macrocyclic conjugation. Analysis of the photophysical properties of this system by steady‐state absorption/fluorescence spectroscopy and transient absorption spectroscopy revealed moderate enhancement in the parameters of the octaphyrin as compared to its non‐bridged octaphyrin congeners, which was attributed to the planarity and rigidity of the macrocycle as imposed by the bridging para‐phenylene unit. Preliminary anion‐binding studies revealed that the protonated macrocycle bound selectively with chloride ions through N?H???Cl hydrogen‐bonding interactions.     

Mechanisms of Tebuconazole Adsorption in Profiles of Mineral Soils

The study attempted to identify the soil components and the principal adsorption mechanisms that bind tebuconazole in mineral soils. The K_F values of the Freundlich isotherm determined in 18 soils from six soil profiles in batch experiments after 96 h of shaking ranged from 1.11 to 16.85 μg^1−1/n (mL)^1/n g⁻¹, and the exponent 1/n values from 0.74 to 1.04. The adsorption of tebuconazole was inversely correlated with the soil pH. Both neutral and protonated forms of this organic base were adsorbed mainly on the fraction of humins. The adsorption of the protonated form increased in the presence of hydrogen cations adsorbed in the soil sorption sites. Fourier transform infrared spectroscopy coupled with the molecular modeling studies and partial least squares regression analysis indicated that the tebuconazole molecule is bound in the organic matter through the formation of hydrogen bonds as well as hydrophobic and π–π interactions. Ion exchange was one of the adsorption mechanisms of the protonated form of this fungicide. The created mathematical model, assuming that both forms of tebuconazole are adsorbed on the organic matter and adsorption of the protonated form is affected by the potential acidity, described its adsorption in soils well.     

The unique properties observed for the unsymmetrical macrocyclic compounds with the highly distorted structure

A new class of aza-macrocycles with the highly distorted structure was found to exhibit unique properties. These macrocycles react with various lithium salts to form lithium complexes and their lithium complexation reactions depend on a substituent on the macrocyclic ring; slower rates and larger equilibrium constants were observed for the macrocycle with a bulkier substituent. The irradiation of these macrocycles by UV light was found to lead to the isomerization, and the photoisomerization rate of macrocycle with the bulky substituent was much faster. The highly distorted structure of these macrocycles makes it much easier to change the conformation of macrocyclic skeleton and these macrocycles have a variety of conformations. The factors to govern this conformational change were therefore explored. The solvent effect was examined by ¹H NMR spectroscopy, because these macrocycles have a strong intramolecular hydrogen bond in the ring. As a result, the solvent was found to have a big effect on the ¹H NMR spectra of macrocycles that could be explained in terms of the conformational change of macrocycle. This finding suggests the solvent to be an important way of controlling the conformation.     

Peripheral modification and basicity of (phthalocyaninato)-copper(II) according to the electronic spectroscopy and quantum chemical calculation data

Singly, doubly, and triply protonated forms of tetra- and octacarboxy (phthalocyaninato)copper(II) derivatives were identified and characterized by electronic absorption spectra and PM3 quantum chemical calculations. Molecules of carboxy-substituted phthalocyanine copper(II) complexes have a distorted nonplanar structure with specific charge distribution over meso-nitrogen atoms. Singly, doubly, and triply protonated complexes at the meso-nitrogen atoms and carboxy groups exist as mixtures of isomers, which is reflected in splitting of the Q band in the electronic absorption spectra and reduction of its symmetry. The formation of bifurcated hydrogen bonds O ... H⁺ ... N _meso and O ... H⁺ ... O between the neighboring substituents was revealed.     

Synthesis and utility of the natural type of porphyrin selectively labeled with carbon-13 at α-meso site

A concise synthesis of the 2,4-dimethyldeuteroporphyrin regiospecifically labeled with ¹³C at the α-meso site was developed. The starting material of ethyl 3,4,5-trimethylpyrrole-2-carboxylate was first converted to a ¹³C-labeled 5,5′-dimethyldipyrromethene with ¹³C formic acid, and the resulting dipyrromethene was coupled with 5,5′-dibromodipyrromethene to afford the ¹³C-labeled porphyrin in 26% yield. The paramagnetic ¹³C NMR measurements of myoglobin with the inversion-recovery method allowed us to detect selectively the α-meso-carbon signal of the iron complex. The heme is symmetric about the α,γ-meso carbon axis to prevent the orientational disorder in protein pocket. These results indicate that the ¹³C-enriched 2,4-dimethyldeuteroporphyrin is a new promising tool to elucidate the structure-function relationship of many hemoproteins.     

Shaping a Porphyrinoid Frame by Heteroatoms Extrusion: Formation of an Expanded [22]Triphyrin(6.6.0)

An aromatic expanded triphyrin, [22]triphyrin(6.6.0) 2 , containing a pyrrole unit, a bipyrrole moiety, and annulene links, was obtained from a tellurium-containing precursor meso-tetraaryl-26,28-ditellurasapphyrin 1 . The reaction path proceeds through an acid-promoted tellurium extrusion from 1 yielding directly 2 , characterized in a dicationic form by X-ray crystallography. In solution the neutral macrocycle 2 reveals flexibility typical for annulenes and it exists as a mixture of conformers that differ by the configuration of the annulene fragments, as proven by ¹H NMR studies and analyzed by DFT methods. The conformation is controlled by protonation state, the nature of an interacting anion, solvent identity, and by interaction with water.     

Tetramethyl‐m‐benziporphodimethene and Isomeric α,β‐Unsaturated γ‐Lactam Embedded N‐Confused Tetramethyl‐m‐benziporphodimethenes

The condensation reaction of α,α′‐dihydroxy‐1,3‐diisopropylbenzene, pyrrole, and an aldehyde leads to the formation of tetramethyl‐m‐benziporphodimethene and outer α‐pyrrolic carbon oxygenated N‐confused tetramethyl‐m‐benziporphodimethenes containing a γ‐lactam ring in the macrocycle. Two isomers with the carbonyl group of the lactam ring either close to (O‐Up) or away from (O‐Down) the neighboring sp³ meso carbon were synthesized and characterized. The single crystal X‐ray diffraction analysis on the regular and γ‐lactam containing tetramethyl‐m‐benziporphodimethenes showed highly distorted macrocycles for all compounds. For O‐Up and O‐Down isomers, dimeric structures, assembling by intermolecular hydrogen‐bonding interactions through lactam rings, were observed in the solid state. Fitting the concentration dependent chemical shifts of the outer NH proton using the non‐linear regression method give a maximum association constant of 108.9 M ^?1 for the meso 4‐methylcarboxyphenyl substituted O‐Down isomer. The DFT calculations concluded that the O‐Up isomer is energetically more stable, and the keto form is more stable than the enol form.     

Siamese‐Twin Porphyrin: A Pyrazole‐Based Expanded Porphyrin of Persistent Helical Conformation

The 3+3‐type synthesis of a pyrazole‐based expanded porphyrin 22 H₄ , a hexaphyrin analogue named Siamese‐twin porphyrin, and its homobimetallic diamagnetic nickel(II) and paramagnetic copper(II) complexes, 22 Ni₂ and 22 Cu₂ , are described. The structure of the macrocycle composed of four pyrroles and two pyrazoles all linked by single carbon atoms, can be interpreted as two conjoined porphyrin‐like subunits, with the two opposing pyrazoles acting as the fusion points. Variable‐temperature 1D and 2D NMR spectroscopic analyses suggested a conformationally flexible structure for 22 H₄ . NMR and UV/Vis spectroscopic evidence as well as structural parameters proved the macrocycle to be non‐aromatic, though each half of the molecule is fully conjugated. UV/Vis and NMR spectroscopic titrations of the free base macrocycle with acid showed it to be dibasic. In the complexes, each metal ion is coordinated in a square‐planar fashion by a dianionic, porphyrin‐like {N₄} binding pocket. The solid‐state structures of the dication and both metal complexes were elucidated by single‐crystal diffractometry. The conformations of the three structures are all similar to each other and strongly twisted, rendering the molecules chiral. The persistent helical twist in the protonated form of the free base and in both metal complexes permitted resolution of these enantiomeric helimers by HPLC on a chiral phase. The absolute stereostructures of 22 H₆ ²⁺, 22 Ni₂ , and 22 Cu₂ were assigned by a combination of experimental electronic circular dichroism (ECD) investigations and quantum‐chemical ECD calculations. The synthesis of the first member of this long‐sought class of expanded porphyrin‐like macrocycles lays the foundation for the study of the interactions of the metal centers within their bimetallic complexes.     

Topochemical polymerisation of assembled diacetylene macrocycle bearing dibenzylphosphine oxide in solid state

Novel diacetylene macrocycles 1 and 2 bearing dibenzylphosphine oxide were synthesised via Eglinton acetylenic intramolecular coupling. The X-ray analysis of crystals of macrocycles 1 and 2 demonstrated that the better-aligned tubular supramolecular structure was formed in macrocycle 1 than in macrocycle 2, which provided the possibility of diacetylene topochemical polymerisation in solid state of macrocycle 1. UV–vis, Raman spectroscopy and X-ray analysis indicated that the crystals of macrocycle 1 could undergo topochemical diacetylene polymerisation only on their surface by light irradiation; differential scanning calorimetry, solid-state ¹³C NMR spectroscopy and solubility test demonstrated that the crystals of macrocycle 1 could undergo diacetylene topochemical polymerisation inside solid by heat. As expected, based on the topological analysis of crystal structure, the crystals of macrocycle 2 could not undergo diacetylene topochemical polymerisation either by light irradiation or heat.     

A colorimetric and fluorescent turn-on chemosensor for Al and its application in bioimaging

The sensing properties of a boron dipyrromethene derivative 1 containing a N,N-(dimethylamino)styryl group at its α-position and an aniline moiety at meso-position were investigated by steady-state UV-vis absorption and fluorescence spectroscopy, which were found to exhibit wavelength ratiometric and large fluorescence enhancement in the presence of Al³⁺ with specific selectivity over other metal ions in aqueous media. Furthermore, confocal fluorescence microscopy experiments demonstrated that 1 could be used as a fluorescent probe for Al³⁺ in living cells.     

Mono-palladium(II) complexes of diamidopyridine-dipyrromethane hybrid macrocycles

The reaction of diamidopyridine-dipyrromethane or dipyrromethene hybrid macrocycles with palladium(II) affords mono-metalated complexes, wherein the metal centre is coordinated to the macrocycle exclusively through pyrrolic nitrogen donor atoms.     

MS/MS Fragmentation Behavior Study of meso-Phenylporphyrinoids Containing Nonpyrrolic Heterocycles and meso-Thienyl-Substituted Porphyrins

Free base and cobalt(II) complexes of six meso-tetraphenylporphyrinoids containing nonpyrrolic heterocycles and of three meso-thienylporphyrins were investigated using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Their fragmentation was studied in a quadrupole ion trap as a function of the porphyrinoid macrocycle structure and compared with the fragmentation behavior of the benchmark compound meso-tetraphenylporphyrin. In situ oxidation of the neutral cobalt(II) complexes under ESI conditions produced singly charged cobalt(III) porphyrinoid ions; the free bases were ionized by protonation. For the porphyrinoids with an intact porphyrin core, the major fragmentation pathways observed were the losses of the meso-substituent (for meso-phenyl groups) and characteristic fragmentations of one or more meso-substituents (for the meso-thienyl group). Complex fragmentation pathways were observed for porphyrinoids with modifications to the porphyrin core but chemically reasonable structures could be assigned to most fragments, thus delineating general patterns for the behavior of pyrrole-modified porphyrins under CID conditions.

CB‐TE2A+·Cl−·3H2O: a short intermolecular hydrogen bond between zwitterionic bicyclo[6.6.2]tetraamine macrocycles

1,4,8,11‐Tetraazabicyclo[6.6.2]hexadecane‐4,11‐diacetic acid (CB‐TE2A) is of much interest in nuclear medicine for its ability to form copper complexes that are kinetically inert, which is beneficial in vivo to minimize the loss of radioactive copper. The structural chemistry of the hydrated HCl salt of CB‐TE2A, namely 11‐carboxymethyl‐1,8‐tetraaza‐4,11‐diazoniabicyclo[6.6.2]hexadecane‐4‐acetate chloride trihydrate, C₁₆H₃₁N₄O₄⁺·Cl⁻·3H₂O, is described. The compound crystallized as a positively charged zwitterion with a chloride counter‐ion. Two of the amine groups in the macrocyclic ring are protonated. Formally, a single negative charge is shared between two of the carboxylic acid groups, while one chloride ion balances the charge. Two intramolecular hydrogen bonds are observed between adjacent pairs of N atoms of the macrocycle. Two intramolecular hydrogen bonds are also observed between the protonated amine groups and the pendant carboxylate groups. A short intermolecular hydrogen bond is observed between two partially negatively charged O atoms on adjacent macrocycles. The result is a one‐dimensional polymeric zigzag chain that propagates parallel to the crystallographic a direction. A second intermolecular interaction is a hydrogen‐bonding network in the crystallographic b direction. The carbonyl group of one macrocycle is connected through the three water molecules of hydration to the carbonyl group of another macrocycle.