Meso-carbon Atoms Research Articles

Synthesis, Structure, Spectral and Redox Properties of Phenoxazine Embedded Heteroporphyrins

A series of phenoxazine embedded heteroporphyrins containing one phenoxazine, two pyrroles and one heterocycle, such as furan, thiophene, selenophene and telluorophene, connected through four meso carbon atoms were synthesized by condensing one equivalent of phenoxazine‐based tripyrrane with one equivalent of the appropriate 2,5‐bis(hydroxymethyl‐p‐tolyl) heterocycle under acid‐catalyzed conditions, and their structure, spectral and electrochemical properties were compared with those of previously reported phenothiazine embedded heteroporphyrins. The X‐ray crystal structure of the phenoxazine embedded selenoporphyrin revealed that the selenophene ring, which is opposite phenoxazine moiety, points outward from the macrocyclic core, and the phenoxazine unit deviated by an angle of 39.47° from the mean plane defined by the four meso carbons atoms. The replacement of the phenothiazine unit in phenothiazine embedded heteroporphyrins with a phenoxazine unit led to significant alteration of the electronic properties of the macrocycles, as reflected in their spectral and electrochemical properties. The absorption spectra of phenoxazine embedded heteroporphyrins showed bathochromically shifted absorption bands, hypsochromically shifted fluorescence bands with decent quantum yields, more facile oxidation and more difficult reduction as compared to the corresponding phenothiazine embedded heteroporphyrins. DFT and TD‐DFT studies were in support of the experimental observations.

Synthesis and properties of 5,10-calixphyrin and its palladium-inserted complex

The reaction of dipyrrolomethane and acetone in the presence of acid and oxidant affords a mixture of 5,15-calixphyrin and 5,10-calixphyrin. The 5,10-calixphyrin readily forms an organometallic Pd(II) complex in 84% yield when treated with Pd(OAc)2 in acetonitrile at reflux. The crystal structure revealed that the 5,10-calixphyrin macrocycle adopted a twisted conformation because of the existence of two sp3-hybridized meso-carbon atoms, which was an impediment in [Formula: see text]-delocalization throughout the macrocycle core. The optimized palladium complex displayed a tetrahedron geometry with reduced distortion throughout the macrocycle. The introduction of palladium metal to the parent calixphyrin scaffold was found to have profound effects on the photophysical and electrochemical properties. Significantly, palladium-inserted 5,10-calixphyrin complex exhibits favorable absorption bands in the visible-near-infrared region with a maximum peak at 672 nm, which is a 148 nm red-shift as compared with that of free base 5,10-calixphyrin. The Pd(II) complex exhibits two reversible reductions and two irreversible oxidations and is more electron-deficient than the corresponding free-base 5,10-calixphyrin. Time-dependent density functional theory studies supported the experimental observations.

Altering the Site of Electron Abstraction in Cobalt Corroles via meso-Trifluoromethyl Substituents

A mono-DMSO cobalt meso-CF3 corrole, formulated as (CF3)3CorCo(DMSO), where (CF3)3Cor is the trianion of 5,10,15-tris(trifluoromethyl)corrole, was synthesized and characterized as to its spectral and electrochemical properties in nonaqueous media with a focus on its coordination chemistry and electronic structure. Cyclic voltammetric measurements showed more facile reductions and difficult oxidations compared to the cobalt triarylcorrole possessing p-CF3Ph units at the meso-positions, a result consistent with the enhanced inductive effect of the electron-withdrawing trifluoromethyl substituents linked directly at the meso-carbon atoms of the macrocycle. The effects of DMSO, pyridine, and cyanide anions (CN-) on the electrochemistry and spectral properties of the compound were investigated, and it was found that only two molar equivalents are needed to form the bis-CN adduct, which exhibited two 1-electron oxidations at 0.27 and 0.95 V vs saturated calomel electrode (SCE) in CH2Cl2/0.1 M TBAP. The sites of electron transfer in the first oxidation and reduction were investigated by spectroelectrochemistry and confirmed that the first electron addition affords a Cor3-CoII complex under all solution conditions independent of the initial coordination and/or electronic configuration (i.e., innocent Cor3-CoIII or noninnocent Cor•2-CoII). In contrast, data for the first oxidation suggests that the site of electron abstraction (ligand or metal) depended upon coordination of the neutral and in situ generated complexes under the various solution conditions, leading to a Co(IV)-corrole3- product for both the bis-pyridine and bis-cyanide adducts.

Doubly Fused Unsymmetrical Calixdicarbahexaphyrins.

Three novel doubly fused unsymmetrical calixdicarbahexaphyrins were synthesized by mild acid-catalyzed (4+2) condensation of dicarbatetrapyrrane with dipyrroethene diol followed by oxidation. The condensation formed doubly fused calixdicarbahexaphyrins instead of π-conjugated dicarbahexaphyrins, due to the unusual fusion of the pyrrole N with the α-carbon of the adjacent pyrrole ring to form a tripentacyclic ring and one usual fusion of the pyrrole N with the adjacent phenylene C to form a fused moiety containing two pentacycles and one hexacycle ring. Both fusions occurred on one side of the macrocycle, making the macrocycles unsymmetric. The crystal structure obtained for one of the macrocycles exhibited a saddle-shaped structure with two benzene rings and four pyrrole rings connected via two ethylene and four methene meso-carbon atoms. The crystal structure also revealed unusual fusions in the macrocyclic framework and the presence of one sp3 carbon that disrupts the π-electron delocalization. 1H, 1H-1H COSY, NOESY, 13C, and HMBC NMR techniques were used to characterize the macrocycles. The absorption spectra of the macrocycles showed one intense sharp band at ∼485 nm along with a shoulder in the lower-energy region, suggesting its non-aromatic nature. Electrochemical studies indicated their electron rich nature, and DFT/TD-DFT studies corroborated the experimental observations.

Synthesis of crown ether appended 25-Oxasmaragdyrins and their BF2-Complexes

Three examples of crown ether appended 25-oxasmaragdyrins were synthesized in 15–20% yields by [3 + 2] oxidative condensation of 16-oxatripyrrane and crown ether appended meso-aryl dipyrromethane in CH2Cl2 in the presence of catalytic amount TFA under inert atmosphere followed by oxidation with DDQ in open air. The crown ether appended 25-oxasmaragdyrins were treated with BF3.OEt2 in CH2Cl2/TEA on hot water bath with 50 °C for 30 min to afford crown ether appended BF2-oxasmaragdyrins in 60–70% yields. The identities of crown ether appended 25-oxasmaragdyrins and their BF2 complexes were confirmed by molecular ion peak in mass spectra and detailed 1D & 2D NMR, absorption, fluorescence and DFT/TD-DFT techniques were used to study the macrocycles. DFT studies revealed that the crown ether appended 25-oxasmaragdyrin and its BF2 complex were almost planar with the meso-phenyl ring containing the crown ether moiety deviated by an angle of 54.86◦ with respect to mean plane defined by three meso carbon atoms. The absorption studies indicated that crown ether appended smaragdyrins and their BF2 complexes showed one or two strong Soret bands in the region of 440–480 nm and four weak Q-bands in 500–750 nm region. The crown ether appended 25-oxasmaragdyrins and their BF2 complexes were weakly fluorescent.

Cleavage of the C-H Bond in Bu3MeP+ by Zinc Porphyrin Dianions: Formation of {ZnII(CH2PBu3)(TPyPH)}- Containing Zn-C(ylide) Bond and the (TPyPH)3- Macrocycle Showing Strong NIR Absorption.

Reduction of {ZnII(TPyP)} to the {ZnII(TPyP)}2- dianions (TPyP: tetra(4-pyridyl)porphyrin) in the presence of Bu3MeP+ allows one to observe the C-H bond cleavage in the methyl group of Bu3MeP+ to form (Bu3MeP+){ZnII(CH2PBu3)(TPyPH)}-·0.337C6H5CH3 (1). Salt 1 is the first coordination complex of neutral CH2PBu3 ylide and metalloporphyrin. The released hydrogen atom attacks the meso-carbon atom of TPyP4- forming a TPyPH3- macrocycle related to phlorins. Decreased symmetry of the TPyPH3- allows the observation of a strong NIR absorption. We discuss the molecular structure, optical, and magnetic properties of 1 together with its formation pathways.

An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols

Cysteine thiols of many cancer-associated proteins are attractive targets of anticancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M-S bond formation, AuMesoIX is unique in that the meso-carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anticancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective antitumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anticancer applications.

Oxygenation of Phenanthriporphyrin and Copper(III) Phenanthriporphyrin: An Efficient Route to Phenanthribilinones.

Photooxidation of copper(III) 5,6-dimethoxyphenathriporphyrin and copper(III) 5,6-dioxophenanthriporphyrin, which contain phenanthrene or dioxophenathrene moieties built into the macrocyclic frameworks, resulted in the regioselective cleavage that afforded organometallic copper(III) complexes of open-chain phenanthribilinone-type acyclic ligands terminated by carbonyl groups. The copper(III) coordinates two carbon atoms of phenantherene (dioxophenanthrene) and two nitrogen atoms of pyrrole and pyrrolone units, preserving the donor sets of the paternal complexes. The primary dioxygen attack is located at the meso carbon atom adjacent to the phenanthrene moiety. Demetalation of copper(III) 21-benzoyl-phenanthribilin-1-one and copper(III) 21-benzoyl-dioxophenanthribilin-1-one yielded mainly two diastereomers [15Z, 20E] and [15Z, 20Z], which differ in the configurations at two Cα-Cmeso double bonds. The regioselectivity of the cleavage, detected in the course of experimental studies, has been substantiated by DFT investigations. The regioselective cleavage of 5,6-dimethoxyphenanthriporphyrin in reaction with basic iron(III) acetate was detected, providing the synthetically efficient methodology to produce 21-benzoyl-dioxophenanthribilin-1-one.

Organocopper(III) Phenanthriporphyrin-Exocyclic Transformations.

5,6-Dimethoxyphenanthriporphyrin 1 and 5,6-dioxophenanthriporphyrin 2 act as suitable organometallic ligands for copper(III), adopting trianionic [CCNN] coordination cores. Under oxidizing conditions, in the presence of methanol, copper(III) phenanthriporphyrin 1-Cu undergoes transformation to copper(III) phenanthriporphodimethene with methoxy substituents attached to two trans meso positions. Addition of acids to 1-Cu yields two isomeric copper(III) isophenanthriporphyrins protonated on one of the meso carbon atoms. Protonation of copper(III) 5,6-dioxophenanthriporphyrin 2-Cu yields the aromatic diprotonated complex 2-Cu-H22+. In the presence of HBF4 2-Cu undergoes borylation at the carbonyl oxygen atoms, forming an aromatic exocyclic boron(III) complex.

Synthesis, Characterization, Sensing, and Coordination Properties of trans‐Homoporphodimethenes

Four different meso‐substituted trans‐homoporphodimethenes containing four five‐membered heterocycles connected through two sp3 meso carbon atoms in a trans fashion and three sp2 meso carbon atoms were synthesized in decent yields through the condensation reactions of 1 equiv. of an appropriate 2,3‐dithienyl‐2‐butenediol with 1 equiv. of meso‐(p‐nitrophenyl)dipyrromethane under mild acid‐catalyzed conditions. All of the trans‐homoporphodimethenes were characterized by HRMS as well as 1D and 2D NMR spectroscopy techniques, and the structure of one of the trans‐homoporphodimethenes was determined by X‐ray crystallography. The crystal analysis indicated that the macrocycle is highly distorted owing to the presence of two meso sp3 carbon atoms and attains a boat conformation. Anion‐sensing studies indicated that these macrocycles can be used as selective fluorescence turn‐on sensors for toxic CN– ions. The trans‐homoporphodimethenes readily form BF2 complexes through treatment with BF3·OEt2 in toluene in the presence of diisopropylethylamine at 70–80 °C for 4 h. The BF2 complexes of the trans‐homoporphodimethenes showed fluorescence bands bathochromically shifted by ca. 80 nm compared with that of BODIPY (4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene) as well as large Stokes shifts.

Iron-Strapped Porphyrins with Carboxylic Acid Groups Hanging over the Coordination Site: Synthesis, X-ray Characterization, and Dioxygen Binding.

A series of myoglobin active site analogues were synthesized and characterized to investigate the dioxygen binding effects of a flexible distal strap over the coordination site. These four synthetic models differ mostly by the shape and polarity of their cavities and also possibly by motion of the distal strap attached to two of the meso carbon atoms. Each of the four models has an intramolecular nitrogen base that axially binds the iron(II) cation inside the porphyrin, but they differ either by the nature of the distal strap or by its mobility. The overhanging distal group is either a generally apolar ethyl malonate group or a polar malonic acid group which is also a strong H-bond donor. It is shown that, in the ferrous complex 2b bearing such an overhung malonic acid group in close proximity to the iron atom, the equilibrium rate for dioxygen binding is significantly enhanced in comparison to that of its ester precursor. In the case of the analogous complex 1b bearing a more mobile distal strap, one of the carboxylic acid groups binds the iron(II) cation, leading to a six-coordinate ferrous complex. Unexpectedly, this complex proved to be high-spin (S = 2) as shown by solid-state magnetic measurements. Whereas this unprecedented complex still binds dioxygen, the formation of the intramolecular six-coordinate complex precluded the measurement of its dioxygen affinity through direct quantitative gas titration monitored by UV-vis spectroscopy. However, in this case, the determination of the kinetic rate constants for dioxygen binding and dissociation by laser flash photolysis allowed the evaluation of the equilibrium rate. Together with three previous X-ray structures of iron complexes in the ααββ conformation, the structure of the cavity and the shape of the relaxed distal strap are also discussed with the consideration of the resolution of X-ray structures of two different free-base ligands in the ααββ conformation, with one bearing the ethyl malonate group and the second one bearing the malonic acid group. A third X-ray structure of the analogous ligand with the overhanging ethyl malonate group in the αβαβ series allows a direct comparison of the distal strap in both geometries. This work reveals that the compound with the overhanging carboxylic acid group which cannot directly interact with the ferrous heme exhibits an increased dioxygen affinity by 2 orders of magnitude versus its ester precursor.

En Route to Stimuli-Responsive Boron-, Nitrogen-, and Sulfur-Doped Polycyclic Aromatic Hydrocarbons.

Replacing both meso carbon atoms of the polycyclic aromatic hydrocarbon (PAH) bisanthene by boron atoms creates an efficient blue fluorophore with a strong electron-accepting character. The corresponding meso-B,S-doped bisanthene exhibits a solvent-dependent green-to-orange photoluminescence and undergoes a reversible reduction at E1/2 =-2.06 V (vs. FcH/FcH(+) ). After oxidation of the sulfur atom, the resulting sulfoxide emits in the blue range of the spectrum, shows only negligible solvatochromism, and a reversible redox transition at E1/2 =-1.74 V. Several related B, N- and B, S-containing PAHs have been prepared following the same modular synthetic procedure and are also described herein. In order to systematically compare their optoelectronic properties, all products have been investigated by cyclic voltammetry as well as UV/Vis absorption/emission spectroscopy.

A Mixed‐Valence Bis‐Phosphorus Complex Entrapped in a Oxatriphyrin(3.1.1) Surrounding

The macrocyclic, porphyrinic environment has been reported as a ligand capable of accommodating different types and numbers of cations. The number of coordinated cations strongly depends on the coordination sphere size, which usually limits the possibility of forming multicationic structures to higher oligomers of macrocycles. Even for structures with enlarged coordination spheres, two interacting phosphorus ions with different oxidation states entrapped in a single organic frame are rarely reported. Oxatriphyrin(3.1.1) adapts its properties to form a mixed‐valence, bis‐phosphorus complex with a P–O–P unit entrapped. The macrocycle adjusts its coordination properties actively by involving the meso carbon atom to bind two phosphorus atoms with different oxidation states. The final complex presents emission properties that are characteristic for a triheterocyclic, fully conjugated fragment but that are tunable by the second PV ion.

Nucleophilic ring-opening of iron(III)-hydroxy-isoporphyrin.

The reactions of iron(III) hydroxyisoporphyrin, chloro[5-(hydroxy)-5,10,15,20-tetrakis(4-methyl)-5,21H-porphinato]iron(III) [Fe(4-Me-HTPI)(Cl)](-), 1 and chloro[5-(hydroxy)-5,10,15,20-tetrakis(4-methoxy-5,21H-porphinato]iron(III) [Fe(4-OMe-HTPI)(Cl)](-), 2 with different O(-), N(-) and S(-) nucleophiles have been performed to understand the reactivity of iron isoporphyrins with nucleophiles. The treatment of iron(III) hydroxy isoporphyrin with alcohols is found to form ring opened 19-benzoyl-1-alkoxy-bilin iron complexes. When alkyl amines were used the formation of ring opened 19-benzoyl-1-alkylamine-bilin iron complexes was observed, but heterocyclic N-nucleophiles such as pyridine and imidazole form benzoyl bilinone iron complexes. No role of oxygen was found in these nucleophilic ring opening reactions. The treatment of a S-nucleophile such as PhSH is found to reduce iron(III)-hydroxyisoporphyrin in the parent iron(III) porphyrin compound. The ring opening products were characterized using electronic and ESI-mass spectroscopy. The mechanism for the formation of ring opening products is based on the formation of a tetrahedral intermediate at the carbon atom near the saturated meso carbon atom similar to the hydrolytic pathway of verdoheme conversion to biliverdin.

Theoretical investigation of the aromaticity and electronic properties of protonated and unprotonated molecules in the series hexaphyrin(1.0.0.1.0.0) to hexaphyrin(1.1.1.1.1.1).

A series of hexaphyrins with different meso-carbon atoms and their protonated structures were investigated using density functional theory (DFT) and time-dependent DFT. Frontier molecular orbitals (FMOs), aromaticity, and electronic spectra were investigated systematically before and after protonation. The FMO energy gaps before and after protonation were different for the antiaromatic molecules, while they were only slightly different for the aromatic molecules. By analyzing the electronic spectra of the aromatic molecules, the absorption peaks in the Q-like and B-like bands were not significantly different before and after protonation. However, the absorption peaks of the antiaromatic molecules were clearly different before and after protonation in both the Q-like and B-like bands. [24]Hexaphyrin (1.0.1.0.1.0) has 24 π-electrons and is Hückel antiaromatic. However, the absorption spectrum of protonated [24]hexaphyrin (1.0.1.0.1.0) showed aromaticity. In addition, these conclusions were generally consistent with the FMOs, nucleus-independent chemical shifts, harmonic oscillator model of aromaticity, and absorption spectra. Although protonated [24]hexaphyrin (1.0.1.0.1.0) has 24 π-electrons and is Hückel antiaromatic, it has Möbius aromaticity because of the single-sided Möbius topological structure. This explains why [24]hexaphyrin (1.0.1.0.1.0) has diatropic ring currents in solvent. To the best of our knowledge, this system is the smallest Möbius aromatic molecule among the many uncoordinated extended porphyrins.

Boron‐Containing Polycyclic Aromatic Hydrocarbons: Facile Synthesis of Stable, Redox‐Active Luminophores

AbstractHerein we show that replacing the two meso carbon atoms of the polycyclic aromatic hydrocarbon (PAH) bisanthene by boron atoms transforms a near‐infrared dye into an efficient blue luminophore. This observation impressively illustrates the impact of boron doping on the frontier orbitals of PAHs. To take full advantage of this tool for the targeted design of organic electronic materials, the underlying structure–property relationships need to be further elucidated. We therefore developed a modular synthesis sequence based on a Peterson olefination, a stilbene‐type photocyclization, and an Si–B exchange reaction to substantially broaden the palette of accessible polycyclic aromatic organoboranes and to permit a direct comparison with their PAH congeners.

Boron‐Containing Polycyclic Aromatic Hydrocarbons: Facile Synthesis of Stable, Redox‐Active Luminophores

Herein we show that replacing the two meso carbon atoms of the polycyclic aromatic hydrocarbon (PAH) bisanthene by boron atoms transforms a near-infrared dye into an efficient blue luminophore. This observation impressively illustrates the impact of boron doping on the frontier orbitals of PAHs. To take full advantage of this tool for the targeted design of organic electronic materials, the underlying structure-property relationships need to be further elucidated. We therefore developed a modular synthesis sequence based on a Peterson olefination, a stilbene-type photocyclization, and an Si-B exchange reaction to substantially broaden the palette of accessible polycyclic aromatic organoboranes and to permit a direct comparison with their PAH congeners.

Synthesis and structural characterization of silver(I), copper(I) coordination polymers and a helicate palladium(II) complex of dipyrrolylmethane-based dipyrazole ligands: the effect of meso substituents on structural formation.

A new class of multidentate dipyrrolylmethane based ditopic tecton, 1,9-bis(3,5-dimethylpyrazolylmethyl)dipyrrolylmethane, containing diethyl (L1) or cyclohexylidene (L2) substituents at the meso carbon atom were readily synthesized in 28-45% yields in two different ways starting from dipyrrolylmethanes. A one dimensional coordination polymer structure ([(L2)Ag][BF4])n was obtained when L2 was treated with AgBF4, whereas the analogous reaction between L1 and AgBF4 afforded the dicationic binuclear metallacycle complex [(L1)2Ag2][BF4]2. In addition, yet another coordination polymeric structure [(L1)CuI]n was obtained from the reaction between L1 and CuI. The analogous reaction of L1 with [Pd(PhCN)2Cl2] afforded the binuclear palladium complex [(L1)2Pd2Cl4] having a double-stranded helicate structure. The observed structural differences are attributed to the effects of the substituents present at the meso carbon atom of the ligand, in addition to the nature of the metal centre, coordination number and the preferred geometry.

Phosphorus complexes of meso-triaryl-25-oxasmaragdyrins.

The aromatic PO2 complexes of meso-triaryl-25-oxasmaragdyrins were synthesized by treating the free base 25-oxasmaragdyrins with POCl3 in toluene/triethylamine at refluxing temperature. The complexes are stable and characterized by X-ray and different spectroscopic techniques. In these complexes, the phosphorus(V) ion was bound to two pyrrolic nitrogen atoms of the smaragdyrin macrocycle and two oxygen atoms in tetrahedral geometry. The X-ray structure revealed that the smaragdyrin macrocycle showed significant distortion upon insertion of a PO2 unit, and the phosphorus atom lies 1.339 Å above the mean plane defined by three meso-carbon atoms of the macrocycle. These complexes absorb strongly in the visible region and are 2.5 times more strongly fluorescent than free base 25-oxasmaragdyrins. The smaragdyrin macrocycle becomes electron-deficient upon complexation with a PO2 unit because these complexes are easier to reduce but difficult to oxidize compared to free base smaragdyrins. We designed and synthesized a covalently linked BODIPY-PO2-smaragdyrin dyad and demonstrated efficient energy transfer from the BODIPY unit to the PO2-smaragdyrin unit.

Calix[4]pyrrole-based ion pair receptors.

Ion pair receptors, which are able to bind concurrently both a cation and an anion, often display higher selectivity and affinity for specific ion pairs than simple ion receptors capable of recognizing primarily either a cation or an anion. This enhancement in recognition function is attributable to direct or indirect cooperative interactions between cobound ions via electrostatic attractions between oppositely charged ions, as well as to positive allosteric effects. In addition, by virtue of binding the counterions of the targeted ion, ion pair receptors can minimize the solvation of the counterions, which can otherwise have a negative effect on the interactions between the receptors and the targeted ions. As a result of their more favorable interactions, ion pair receptors are attractive for use in applications, such as extraction and sensing, where control of the binding interactions is advantageous. In this Account, we illustrate this potential in the context of ion pair receptors based on the calix[4]pyrrole scaffold. Both simple ditopic ion pair receptors, containing sites for the recognition of a single anion and single cation, and so-called multitopic ion pair receptors will be discussed. The latter systems differ from conventional, so-called ditopic ion pair receptors in that they contain more than one binding site for a given targeted ion (e.g., a cation). This permits a level of selectivity and control over binding function not normally seen for simple ion or ion pair receptors containing one or two binding sites, respectively. Calix[4]pyrroles are macrocyclic compounds consisting of four pyrrole units linked via fully substituted sp(3) hybridized meso carbon atoms. They are effective receptors for Lewis basic anions (e.g., halides) in typical organic media and under certain conditions will recognize ion pairs containing charge diffuse cations, such as a small alkylammonium, imidazolium, or cesium cations. The calix[4]pyrrole framework is further attractive in that it is relatively easy to modify. In particular, functionalization of the β-pyrrolic carbon and meso-carbon atoms with simple crown ethers or calix[4]arene crown ethers can produce heteromultitopic ion pair receptors containing more than two cation binding sites. This allows the interactions between receptors and ions to be manipulated on a higher level than can be achieved using simple ion receptors or heteroditopic ion pair receptors and has made these systems attractive for use in ion transport, recognition, and extraction. Recent progress in developing calix[4]pyrroles as both multitopic and more conventional ion pair receptors is summarized in this Account. The emphasis will be on our own work.