Macrocyclic Systems Research Articles

Structural and Electronic Effects in the Metalation of Porphyrinoids. Theory and Experiment

The structure-reactivity relationships in metalation reactions of porphyrinoids have been studied using experimental and theoretical methods. A series of eight porphyrinoic ligands, derivatives of chlorophylls, was prepared in which both the peripheral groups and the degrees of saturation of the macrocycle were systematically varied. To reveal the solvent and structural factors which control the interactions of these macroligands with metal centers, their interactions with reactive Zn(2+) and inert Pt(2+) ions were investigated using absorption spectroscopy. In parallel, quantum chemical calculations (density functional theory, DFT) were performed for the same set of molecules to examine the influence of structural and electronic factors on the energy of the frontier orbitals, the nucleophilicity/electronegativity of the macrocycle, its hardness, and conformation. These static descriptors of chemical reactivity, relevant to metalation reactions, were verified against the results obtained in the experimental model. The experimentally obtained kinetic data clearly show that the solvent has a crucial role in the activation of the incoming metal center. In terms of chelator structure, the largest effects concern the size of the delocalized pi-electron system and the presence of side groups. Both the DFT calculations and experimental results show the strong influence of the macrocycle rigidity and of the peripheral groups on the chelating ability of porphyrinoids. In particular, the peripheral functionalization of the macrocyclic system seems to drastically reduce its reactivity toward metal ions. The effect of peripheral groups is two-fold: (i) a lower electron density on the core nitrogens, and (ii) increased rigidity of the macrocycle. The outcomes of the theoretical and experimental analyses are discussed also in terms of their relevance to the mechanism of biological metal insertion in the biosynthesis of heme and chlorophyll.

Isocyanoacetate Derivatives: Synthesis, Reactivity, and Application

The sphingolipid bases, D-erythro- and D-threo-sphingosines, are the target molecules that have been synthesized to demonstrate the efficiency of a new methodology to control both absolute and relative configurations in acyclic systems. Tubulysins are compounds of extraordinary potency, rapidly degrading the tubulin cytoskeleton, with tubulysin D being the most active tubulin-modifier known so far. Among other isonitriles, isocyanoacetate derivatives occupy an important place in the field of synthetic application and reaction diversity, which makes them strongly attractive objects for investigation. The unique multifunctional nature of isocyanoacetic acid derivatives opens up a range of exciting reactions, especially tandem/cascade processes for the synthesis of complex cyclic and macrocyclic systems. Multicomponent chemistry of isocyanoacetates is also a powerful instrument to access different classes of biochemically relevant compounds such as peptides, peptide molecules, and nitrogen heterocycles.

ChemInform Abstract: Heavy Metal Ion Chemistry of Linked Macrocyclic Systems Incorporating Oxygen and/or Sulfur in Their Donor Sets

Abstract The heavy metal chemistry of linked macrocyclic ligand systems incorporating all oxygen, all sulfur, oxygen and nitrogen, oxygen and sulfur; nitrogen and sulfur as well as oxygen, nitrogen and sulfur in their donor sets is reviewed.

Electrophilic Reaction of Ag(III) N-Confused Porphyrin with Alcohols

Experimental studies demonstrated that alcohols and amines can undergo a CF(3)COOAg-catalyzed nucleophilic addition at the outer C=N position of Ag(III) NCPs, leading to C-3-alkoxylated Ag(III) NCPs, which supports the computational result that the C=N bond on the periphery of Ag(III) NCPs is partially isolated from the 18 pi-electron macrocyclic conjugation system and is the active electrophilic center.

Macrocyclic oligoarylamine-based spin system

Alternating meta- and para-phenylene-linked oligoarylamines are considered as promising molecular parts for the molecule-based electronics and/or spintronics due to their intriguing electronic and magnetic properties. From the magnetic viewpoint, a -meta-phenylene linker plays a crucial role in ensuring the effective ferromagnetic interaction, while para-phenylene linker plays an important part in stabilizing the spin-containing aminium radical cations. Of the meta–para and all-meta oligoarylamines prepared so far, the macrocyclic oligoarylamines are structurally defined, and therefore we can employ them as the component pieces to prepare the two- or three-dimensionally structured oligoarylamines. The spin electronic properties of polycationic species generated from two kinds of macrocyclic oligoarylamines, which will be able to be extended into the 2D multi-spin molecular systems, are described on the basis of the pulsed electron spin resonance (ESR) measurements.

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-A 2- and 5,10-AB-2,3,7,8,12,13,17,18-octaethylporphyrins bearing donating groups such as –OMe and –NMe 2 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.

α-Cyclodextrins reversibly capped with disulfide bonds

Per-O-methyl-6I,6IV-disulfanyl-6I,6IV-dideoxy-α-cyclodextrin undergoes air oxidation at pH 9 to exclusively form a monomeric species having an intramolecular disulfide linkage capping the C6I and C6IV positions. In contrast, its non-methylated analogue, 6I,6IV-disulfanyl-6I,6IV-dideoxy-α-cyclodextrin, gives a mixture of monomeric and dimeric species under the same conditions. Molecular models show that in both cases of the monomeric species, the disulfide bonds effectively close the primary rims of the cyclodextrin cavities. The disulfide bonds of the capped cyclodextrins could be cleaved by reduction with dithiothreitol. Thus, the macrocyclic system can interchange the open-ended and cup-like forms by the application of external stimuli.

10.1007/s11176-008-2004-z

Effect of ortho-methyl groups in the benzene rings of the macrocyclic matrix on the chemistry of cavitands with phosphorous amide bridges in the upper rim is studied. The presence of ortho-methyl groups is shown to prevent formation of phosphacavitands of C 4v symmetry and favor formation of macrocyclic systems of C 2v symmetry, enhance solubility of phosphacavitands in organic solvents, hinder oxidation of phospha(III)cavitands and decrease the yield of phospha(V)cavitands, prevent formation of binuclear molybdenum complexes of phosphorous amide cavitands, and favor formation of their tetranuclear analogs.

Hydrogen bonded aryl amide and hydrazide oligomers: a new generation of preorganized soft frameworks

Hydrogen bonded aryl amide and hydrazide foldamers may adopt folded, zigzag or other extended conformations, depending on the positions of the amides and hydrogen bonding sites on the aromatic rings. In recent years, several series of such preorganized frameworks have been developed as efficient acyclic receptors for binding both neutral and ionic guests. The backbones can also be readily modified and appended with discrete functional units. Therefore, they have also been widely utilized in designing new molecular tweezers, for assembling ordered supramolecular architectures, and for directing the formation of complicated macrocyclic systems. This feature article highlights the recent advances, with a primary focus on our own work.

Form leading to function

In a Dutch city famous for the treaty that led to the creation of the European Union, delegates gathered at a conference to discuss recent advances in the chemistry of macrocyclic and supramolecular systems.

ChemInform Abstract: Synthesis of Macrocyclic Systems from 4,4′‐Diamino‐3,3′‐bi‐1,2,5‐oxadiazole and 3(4)‐Amino‐4(3)‐(4‐amino‐1,2,5‐oxadiazol‐3‐yl)‐1,2,5‐oxadiazole 2‐Oxides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The synthesis of carbon-linked bisbenzylisoquinolines via ruthenium-mediated olefin-metathesis

Novel laudanosine dimers in which two laudanosine units are linked at C-2′ via a two and four-carbon linker have been prepared using ruthenium-mediated olefin-metathesis. In addition, a second four-carbon linker between the two isoquinoline N-atoms was also present leading to a novel macrocyclic ring system. Five of these compounds showed higher cytostatic activity on three cancer cell lines than thalicarpine.

Synthesis, characterization and spectroscopic properties of novel periphery – functionalized unsymmetrical porphyrazines containing mixed dithienylpyrrolyl and dimethylamino groups

Following our previous report on a novel class of C 4 symmetric porphyrazines bearing 2,5-dimethylpyrrolyl and methyl(3-pyridylmethyl)amino groups in the periphery, here we report the synthesis and characterization of unsymmetrical porphyrazines with peripheral 2,5-di(2-thienyl)pyrrolyl and dimethylamino groups that break the molecular C 4 symmetry. The porphyrazines were prepared via macrocyclization reactions of a dinitrile precursor. Variable-temperature 1H NMR experiments, single crystal X-ray work and UV–Vis spectra in different solvents of the unsymmetrical magnesium porphyrazine provided information on the structural and electronic features of the entire macrocyclic system. A detailed discussion of the UV–Vis spectra in different solvents emphasizes the role played by the extended peripheral 2,5-di(2-thienyl)pyrrolyl substituent.

Synthetic Applications of Intramolecular Aza-Wittig Reaction for the Preparation of Heterocyclic Compounds

A review focused on recent advances in intramolecular aza-Wittig reaction of phosphazenes with several carbonyl or analogous compounds is reported. Phosphazenes afford intramolecular aza-Wittig reaction with different groups within the molecule as aldehydes, ketones, esters, thioesters, amides, anhydrides and sulfimides. One of the most important applications of this reaction is the synthesis of a wide range of heterocyclic compounds, ranging from simple monocyclic compounds to complex polycyclic and macrocyclic systems.

Separation of hexahistidine fusion proteins with immobilized metal ion affinity chromatographic (IMAC) sorbents derived from MN+‐tacn and its derivatives

The capabilities of a new class of immobilized (im) metal ion chelate complexes (IMCCs), derived from 1,4,7-triazacyclononane (tacn), bis(1,4,7-triazacyclononyl) ethane (dtne) and bis(1,4,7-triazacyclononyl)propane (dtnp) complexed with the borderline metal ions Cu(2+), Ni(2+), Zn(2+), Mn(2+), Co(2+), and Cr(3+), for the purification of proteins have been investigated. In particular, the binding behavior of a model protein, the C-terminal hexahistidine tagged recombinant fusion protein Schistosoma japonicum glutathione S-transferase-Saccharomyces cerevisiae mitochondrial ATP synthase delta-subunit (GST-deltaATPase-His(6)), with these new immobilized metal ion affinity chromatographic (IMAC) sorbents was compared to the properties of a conventional sorbent, derived from immobilized Ni(II)-nitrilotriacetic acid (im-Ni(2+)-NTA). Investigations using the recombinant GST-deltaATPase-His(6) and recombinant S. japonicum glutathione S-transferase (GST) lacking a hexahistidine tag have confirmed that the C-terminal tag hexahistidine residues were required for the binding process to occur with these IMAC systems. The results also confirm that recombinant fusion proteins such as GST-deltaATPase-His(6) can be isolated in high purity with these IMAC systems. Moreover, these new macrocyclic systems manifest different selectivity features as a function of pH or ionic strength when compared to the conventional, unconstrained iminodiacetic acid (IDA) or NTA chelating ligands, complexed with borderline metal ions such as Cu(2+) or Ni(2+), as IMAC systems.

Copper(II) Interaction with Mono-, Bis- and Tris-Ring N3O2 Macrocycles: Synthetic, X-ray, Competitive Membrane Transport, and Hypochromic Shift Studies

New N-phenyl (L(1)), azo-coupled (L(2)), and tri-linked (L(3)) substituted derivatives of a parent dibenzo-N(3)O(2) macrocycle, 1,12,15-triaza-3,4:9,10-dibenzo-5,8-dioxacycloheptadecane (L(4)), have been synthesized. Competitive seven-metal transport studies across a bulk chloroform membrane employing an aqueous source phase containing equal molar concentrations of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Ag(I), and Pb(II) as their nitrate salts have been performed using both L(1) and L(3) as the ionophore, with the results discussed in terms of those obtained previously for related mono-ring (L(5)) and di-linked (L(6)) macrocyclic systems. Sole transport selectivity for Cu(II) was observed in each case. On a per macrocyclic cavity basis the tri-linked analogue L(3) gave less efficient Cu(II) transport than its monomeric or di-linked analogues. At least in part, this may reflect the tendency of tri-linked derivative L(3) to form a 2:1 complex (metal/ligand) with Cu(II) under the conditions employed; such a stoichiometry was demonstrated to occur in acetonitrile using both spectrophotometric titration and Job plot procedures. The azo-coupled derivative (L(2)) yields a red solution (lambda(max) = 495 nm, epsilon(max) = 23000 M(-1) cm(-1)) and undergoes significant hypochromic metal-induced shifts (Delta lambda(max) = 54-174 nm) on metal addition. Cu(II) induces the largest shift (Delta lambda(max) = 174 nm), corresponding to a color change from red to pale-yellow. The X-ray structures of red L(2) x HNO(3) together with its Cu(II) complexes, [Cu(L(2))NO(3)]NO(3) x CH(2)Cl(2) (6) (pale-yellow) and [{Cu(L(2))}(2)(mu-OH)(2)](ClO(4))(2) x 2 CH(2)Cl(2) x 2 H(2)O (7) (dark-red), are reported. The structural determinations have allowed insight into the structure-function relationships governing the observed color variation between these species.

Intramolecular interactions and photoinduced electron transfer in isoalloxazine-naphthalene bichromophores

The synthesis, the structural characterization and electrochemical and photophysical properties of new linear ( OFn) and macrocyclic ( MFn) bichromophoric systems containing one flavin and one naphthalene moiety, separated by (CH 2) n alkyl chains ( n = 4 or 6), are reported. The electrochemical properties of OF4, OF6, MF4, MF6 were investigated by cyclic voltammetry (CV) in ultra-dry THF and compared with the model compounds containing either the flavin unit ( FL6) or the monomethoxy- ( mona) and dimethoxy naphthalene ( dmona) derivatives, respectively. While only minor ground-state interactions were evidenced between the chromophores in the voltammetric curves and absorption spectra of bichromophores, luminescence data evidenced intramolecular photoinduced electron transfer processes as main deactivation routes of flavin-centered excited states. The rates of the intramolecular photoinduced electron transfer, involving the oxynaphthalene moieties as electron donors, were finally determined.

Synthesis and Applications of a New Polysiloxane-Immobilized Macrocyclic Ligand System

Insoluble porous solid, macrocyclic 22-membered ring, 1-oxa-6,9,12,15,18-pentaaza-2,22-disilacyclododocosane polysiloxane ligand system has been prepared by the reaction of a macro-silane agent with tetraethylorthosilicate. The macro-silane agent was prepared by the reaction of imino-bis(N-2-aminoethylacetamide) ligand with 3-iodopropyltrimethoxysilane in 1:3 molar ratio. The new prepared polysiloxane system exhibits variable potentials for the extraction of metal ions (Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ag+, Cd2+, Hg2+, and Pb2+) from aqueous solutions. The ligand system shows high capacity to extract silver, lead, and mercury. Chemisorption of the metal ions by the ligand system at the optimum conditions was found in the order Ag + > Pb2+ > Hg2+ > Cu2+ > Ni2+ > Fe3+ > Co2+ > Cd2+ > Zn2+.

Hydrogen bonding between carboxylic acids and amide-based macrocycles in their host–guest complexes

For 12- and 13-membered macrocycles in which two amide linkages are integrated in the macrocyclic ring systems, the formation of 1:1 host–guest complexes with acetic and benzoic acids has been confirmed by NMR titrations. The complex formation occurs with the formation constants of 8–27 M− 1, under competition with the dimerisation of acid molecules. Benzoic acid tends to form more stable complexes than acetic acid. The binding force is due to a pair of hydrogen bonds, Ocarboxyl–H…O = Camide and C = Ocarboxyl…H–Namide, between the carboxyl group of a guest molecule and the amide group of a host molecule. The former bond is stronger than the latter, and defines the stability of the complexes. The formation of the pair of hydrogen bonds is accompanied by the conformational conversion of the amide group from the trans-form to the cis-form. The influence of such a conversion on the internal molecular motion is observed as a slight broadening of signal width. For 12- and 13-membered macrocycles in which two amide linkages are integrated in the macrocyclic ring systems, the formation of 1:1 host–guest complexes with acetic and benzoic acids has been confirmed by NMR titrations. The binding force for the complex formation is due to a pair of hydrogen bonds, Ocarboxyl–H…O = Camide and C = Ocarboxyl…H–Namide. The former bond is stronger than the latter and dominates the hydrogen-bond formation. The formation of the pair of hydrogen bonds is accompanied by the conformational conversion of the amide group from the stable trans-form to the less stable cis-form.

The synthesis of carbon linked bis-benzylisoquinolines using Mizoroki–Heck and Sonagashira coupling reactions

Novel laudanosine dimers in which two laudanosine units are linked at C-2′ via a two or three-carbon linker (alkane, alkene or alkyne) have been prepared using palladium-catalysed cross-coupling reactions (Mizoroki–Heck and Sonagashira reactions). In one example, a second three-carbon linker between the two isoquinoline N-atoms was also present leading to a novel macrocyclic ring system.