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At least 343 records · Page 19Linked to original sources
PubMed2006

A hydrogen-bonding-modulated molecular rotor: environmental effect in the conformational stability of peptidomimetic macrocyclic cyclophanes.

The conformational behavior of 16- to 18-membered ring peptidomimetic p-cyclophanes 1a,b-3a,b has been studied by NMR. The cycles bearing 16 and 17 atoms showed a dynamic process within the NMR time scale, produced by the rotation of the aromatic p-diphenylene moiety with respect to the macrocyclic main plane. The temperature dependence of 1H NMR spectra has been studied in order to get activation parameters of the energetic barrier for the process (VT-NMR and line shape analysis). The rate of the movement clearly depends on the macrocyclic ring size and the nature of the peptidomimetic side chain. Entropic and enthalpic contributions to the free energy of activation are discussed. The rotation of the aromatic ring is closely related to the intramolecular hydrogen bonding pattern, as suggested by temperature factors of NH chemical shifts (DeltadeltaNH/DeltaT) and molecular modeling. The interconnected roles of the solvation and the intramolecular H-bonds have been established by measurements (VT-NMR and DeltadeltaNH/DeltaT) in environments of different polarities and H-bonding abilities. We concluded that the conformational stability of the systems directly depends on the stability of the intramolecular H-bonding pattern. We finally showed how one of these peptidomimetics behaves as a methanol-dependent artificial molecular rotor. In this simple molecular device, the well-defined molecular rotation is tuned by the competition between intramolecular hydrogen bonds and interactions with the solvent.

Ethers, Cyclic↗
PubMed2006

Synthesis of new macrocyclic chiral manganese(III) Schiff bases as catalysts for asymmetric epoxidation.

We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III) salen complexes. The developed reaction pathway allows the modulation of the different key groups, namely, the chiral diimine, the bulky substituents in positions 3 and 3', and the linker used in the macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available structural variations. The catalytic properties of the catalysts (5 mol %) were improved for the asymmetric epoxidation of 2,2'-dimethylchromene with NaOCl or H2O2 as oxygen atom donor. A large range of enantiomeric excesses was obtained (ee values from 30% to 96%), depending on the features and the stability of the complexes. The most efficient catalyst, in terms of stereoinduction (ee value = 96%), contains a diiminocyclohexyl moiety, ethyl groups in positions 3 and 3', and a short polyether junction arm.

Catalysis↗
PubMed2006

Synthesis of N3,N'3-polymethylene-bis-hydantoins and their macrocyclic derivatives.

An efficient and straightforward two-step approach toward N3,N'3-polymethylene-bis-hydantoins was developed. As a first step, a pyroglutamate is reacted with a diisocyanate to produce a bis-carbamoyllactam. The second step is a double-ring transformation by treatment of this bis-carbamoyllactam with KOtBu in ethanol. In this fashion N3,N'3-polymethylene-bis-hydantoins are produced in two quantitative steps and under very mild conditions. When properly derivatized, these compounds can be converted to their macrocyclic derivatives upon treatment with 5 mol % of second-generation Grubbs' catalyst. These macrocyclic derivatives are so far not described in the literature. It was proven that exclusively (E)-isomers are formed.

Hydantoins↗
PubMed2006

Aza-beta3-cyclohexapeptides: pseudopeptidic macrocycles with interesting conformational and configurational properties slow pyramidal nitrogen inversion in 24-membered rings!

Among pseudopeptidic foldamers, aza-beta3-peptides have the unique property to possess nitrogen stereocenters instead of carbon stereocenters. As the result of pyramidal inversion at N(alpha)-atoms along the backbone, they behave as a set of C8-based secondary structures in equilibrium. This structural modulation is exploited here to prepare 24-membered macrocycles with great efficiency. Both crystal structures and spectroscopic data establish that aza-beta3-cyclohexapeptides adopt a highly organized conformation where the relative configuration of chiral nitrogen atoms is alternated. This makes them an interesting scaffold as the stereocontrol occurs spontaneously through the cyclization. These compounds reveal an unprecedented slow pyramidal nitrogen inversion in macrocycles. Pyramidal ground state stabilization, hindered rotation, steric crowding, and H-bond cooperativity are proposed to participate in this striking phenomenon. The equilibrium between invertomers of aza-beta3-cyclohexapeptides is reminiscent of the interchange between the two chair forms of cyclohexane.

Aza Compounds↗
PubMed2004

SAMs of shape-persistent macrocycles: structure and binding on HOPG and Au(111).

Self-assembled monolayers of shape-persistent macrocycles have been adsorbed on highly oriented pyrolytic graphite and Au(111) substrates. Their structure and binding characteristics have been investigated by scanning tunneling microscopy, X-ray photoelectron spectroscopy, and ultraviolet photoelectron spectroscopy experiments. Special functionalization of the macrocycles for the first time has enabled their self-assembling and binding on a metal substrate and opened a new route for new functional nanostructures.

Gold↗
PubMed2004

An evanescent-field-driven self-assembled molecular photoswitch for macrocycle coordination and release.

Two self-assembled monolayer (SAM) films containing the photoswitchable 4-pyridylazophenoxy chromophore have been deposited onto a gold-coated glass substrate. One film contains the chromophore as a single component, 1 SAM, and the other is doped with a nonphotoactive component as a 1:1 mixture, 2 SAM. The reversible photoswitching performances of 1 SAM and 2 SAM via the evanescence field using light of appropriate wavelengths have been investigated by UV spectroscopic and electrochemical monitoring. In principle, the trans-form SAMs present a coordinating surface, the "on" state, that can be switched "off" in the cis form. This has been illustrated by immersing both the as-deposited (trans form) SAMs and the photoswitched (predominantly cis form) SAMs into solutions of cobalt and zinc tetraphenylporphyrin (CoTPP and ZnTPP, respectively) and an octaoctyl-substituted cobalt phthalocyanine. In a further phase of this study, the remote control of binding events at the surface of the SAMs has been demonstrated through evanescent-field-driven photoswitching of trans-form SAMs coordinated at the surfaces with examples of these metallomacrocycles. This photoswitching was undertaken with the constructs immersed in neat toluene, and the macrocycles were released from the surface into the solvent. The release was measured by spectroscopic monitoring of the material remaining on the constructs. The study was extended to develop an in situ release/coordination cycle. Thus, irradiation of a construct of ZnTPP bound to the surface of trans-form 2 SAM using waveguided light at 365 nm releases the macrocycle into a toluene solution of ZnTPP. Further irradiation of the SAM, now in its cis form, with waveguided 439 nm light regenerates the trans form, which recoordinates ZnTPP from the solution. The results demonstrate the potential for using waveguided light to control molecular events within and at the surfaces of SAM constructs.

Electrochemistry↗
PubMed2006

One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3+2] cycloaddition.

By combining three appropriately designed simple substrates, a programmed sequence involving an alpha-isocyano acetamide-based three-component reaction followed by a copper-catalyzed intramolecular [3+2] cycloaddition of alkyne and azide took place to afford complex macrocycles in moderate to good yields. One macrocycle and two heterocycles were produced with concurrent formation of five chemical bonds in this operationally simple process.

Macrocyclic Compounds↗
PubMed2006

Four new macrocyclic trichothecenes from two strains of marine-derived fungi of the genus Myrothecium.

Three new macrocyclic trichothecenes, named 12'-hydroxyroridin E (1), roridin Q (2), and 2',3'deoxyroritoxin D (3), were isolated from the marine-derived fungus Myrothecium roridum TUF 98F42, and a new macrocyclic trichothecene, named roridin R (4), was isolated from Myrothecium sp. TUF 02F6 together with roridins A and H and isororidin E. The structures of new compounds were determined on the basis of their spectral data. Compound 2 possessed a unique ether moiety at the 13' position of 1. Compound 4 was a 2',3'-dihydro-2'-hydroxy derivative of roridin H. The IC50 values of compounds 1, 2, and 4 against the murine leukemia cell line L1210 were 0.19, 31.2, and 0.45 microM, respectively. Compound 3 showed antiyeast activity to Saccharomyces cerevisiae at 1 microg/disc (inhibition zone: 12.2 mm), which was about 10 time more active than roritoxin D (10.2 mm at 10 microg/disc).

Antineoplastic Agents↗
PubMed2004

NMR relaxometric study of new Gd(III) macrocyclic complexes and their interaction with human serum albumin.

Five novel Gd(iii) complexes based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their (1)H and (17)O NMR relaxometric properties investigated in detail. The complexes have been functionalised on the secondary nitrogen atom of the macrocyclic ring with different pendant groups for promoting their ability to interact non-covalently with human serum albumin (HSA). The analysis of the proton relaxivity, measured as a function of pH and magnetic field strength, have revealed that the three complexes bearing a poly(ethylene glycol)(PEG) chain possess a single coordinated water molecule, whereas the complexes functionalised with 1-[3-(2-hydroxyphenyl)]-propyl and 1-[3-(2-carboxyphenyloxy)]-propyl pendant groups have two inner sphere water molecules. The water exchange rates, measured by variable temperature (17)O NMR, cover a broad range of values (from 18 to 770 ns) as a function of their charge, the chemical nature of the substituent and its ability to organize a second sphere of hydration near the water(s) binding site. All the complexes have shown some degree of interaction with HSA, with a stronger binding affinity measured for those bearing an aromatic moiety on the pendant group. However, upon binding the expected relaxation enhancement has not been observed and this has been explained with the displacement of the coordinated water molecules by the protein and formation of ternary adducts.

Gadolinium↗
PubMed2005

Formation and dissociation kinetics of Cu(II) and Ni(II) complexes with N2S2-macrocycles.

The kinetics of the formation and dissociation of the Cu(2+) and Ni(2+) complexes with a series of N(2)S(2) macrocycles, in which the ring size and the geometry of the arrangement of the donor groups have been varied, have been measured at 25 [degree]C and I= 0.5 (KNO(3)). Both the deprotonated (L) and the monoprotonated (LH(+)) form of the ligands are reactive species in the formation step. In their deprotonated form, first bond formation, in some cases supported by an ICB effect, is rate determining, independently of the ring size. In the monoprotonated form, we find slower rates, due to the charge repulsion and/or conformation changes induced by hydrogen bonds. In contrast the mechanism of the dissociation is very dependent on the ring size. The complexes with the smaller rings react as flexible open-chain ligands directly with H(+). In contrast, the complexes with the larger rings react in a similar way as rigid ligands: first the metal amine bond slowly dissociates so that the free electron pair of the amine can take the "out conformation" and then it is protonated. The 14-membered macrocycle L(3) forms complexes in which the metal ions are ideally coordinated so that their dissociation becomes extremely slow.

Copper↗
PubMed2005

Tetrakis(imidazolium) macrocyclic receptors for anion binding.

New (tetrakis)imidazolium macrocyclic receptor systems of variable cavity size have been synthesised by stepwise alkylation reactions of bis(imidazolium) precursor compounds. Proton NMR titration studies reveal the macrocycles to strongly bind halide and benzoate anions, with two receptor systems displaying notable selectivity for fluoride in competitive acetonitrile-water (9:1) solvent media.

Anions↗
PubMed2006

Design of base metal extractants. Part 1. Inter-ligand hydrogen bonding in the assembly of pseudo-macrocyclic bis(aminosulfonamidato)M(II) complexes.

Monosulfonyl derivatives of simple 1,2- and 1,3-diamines (R2HN-R-NHSO2R1 = L) have been shown to be easily deprotonated to give neutral 2:1 complexes, [M(L - H)(2)], with Co(II), Ni(II), Cu(II) or Zn(II). The Ni(II) and Cu(II) complexes with deprotonated N-tosyl-1,2-diaminoethane have a planar N4(2-) donor set and a 14-membered pseudo-macrocyclic structure based on head-to-tail S=O...H-N((amine)) bonding between the two bidentate ligands. In the related tetrahedral Zn(II) complex the ends of the mutually perpendicular bidentate N2- units are too far apart to form a cyclic H-bonded system. X-Ray structure determinations on five free ligands provide evidence for extensive inter-molecular H-bonding, which in the case of N-tosyl-1,3-diaminopropane and its N'-tert-butyl derivative involves formation of dimeric 16-membered pseudo-macrocycles. Despite favourable inter-ligand H-bonding in the neutral 2:1 complexes, these ligands are relatively weak extractants, showing >50% loading of Cu(II) in "pH-swing" equilibria, 2L(org)+ M2+ = [M(L - H)2](org)+ 2 H+, only when the pH of the aqueous phase is raised above 4.

Crystallography, X-Ray↗
PubMed2006

Labelling monoclonal antibodies with macrocyclic radiometal complexes. A challenge for coordination chemists.

The technique consisting of labelling antibodies with radionuclides is a promising approach for the diagnosis and therapy of human cancers. In this paper the chemical aspects of radiolabelling with macrocyclic metal complexes are dealt with. The choice of the radioisotope, its coordination chemistry, the design of the bifunctional macrocyclic ligand, and its attachment to the monoclonal antibody are discussed. Finally several newer ideas for a better application are presented.

Antibodies, Monoclonal↗
PubMed2005

Protein recognition of macrocycles: binding of anti-HIV metallocyclams to lysozyme.

The macrocyclic antiviral drug xylyl-bicyclam blocks entry of HIV into cells by targeting the CXCR4 coreceptor, a seven-helix transmembrane G-protein-coupled receptor. Its affinity for CXCR4 is enhanced by binding to Cu2+, Ni2+, or Zn2+. Metallocyclams have a rich configurational chemistry and proteins may bind selectively to specific metallocyclam configurations. Our studies of lysozyme reveal structural details of protein-metallocyclam interactions that are important for receptor recognition. Solution NMR studies show that Cu-cyclam interacts with specific tryptophan residues of lysozyme (Trp-62, Trp-63, and Trp-123). Two major binding sites for both Cu-cyclam and Cu2-xylyl-bicyclam were detected by x-ray crystallography. In the first site, Cu2+ in one cyclam ring of Cu2-xylyl-bicyclam adopts a trans configuration and is coordinated to a carboxylate oxygen of Asp-101, whereas for Cu-cyclam two ring NH groups form H bonds to the carboxylate oxygens of Asp-101, stabilizing an unusual cis (folded) cyclam configuration. For both complexes in this site, a cyclam ring is sandwiched between the indole side chains of two tryptophan residues (Trp-62 and Trp-63). In the second site, a trans cyclam ring is stacked on Trp-123 and H bonded to the backbone carbonyl of Gly-117. We show that there is a pocket in a model of the human CXCR4 coreceptor in which trans and cis configurations of metallobicyclam can bind by direct metal coordination to carboxylate side chains, cyclam-NH...carboxylate H bonding, together with hydrophobic interactions with tryptophan residues. These studies provide a structural basis for the design of macrocycles that bind stereospecifically to G-coupled and other protein receptors.

Animals↗
PubMed1999

Liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry enantiomeric separation of dl-threo-methylphenidate, (Ritalin) using a macrocyclic antibiotic as the chiral selector.

Vancomycin, a macrocyclic antibiotic, is an amphoteric glycopeptide produced by Streptomyces orientalis which has proven to be a viable chiral selector for high performance liquid chromatograph (HPLC) (D. W. Armstrong, Y. Tang, S. Chen, Y. Zhou, C. Bagwill and J-R. Chen, Anal. Chem. (1994; 66: 1473). While it is related to other glycopeptide antibiotics, vancomycin has a number of unique structural features, including 18 stereogenic centers, five aromatic rings, and two side chains one of which is a carbohydrate dimer. Therefore, a vancomycin-based stationary phase appears to be multimodal in that it can be utilized in both normal-phase and reversed-phase liquid chromatography. Consequently, the enantiomeric separation may be operative via several mechanisms, including pi-pi complexation, dipole stacking, inclusion, hydrogen bonding, or combinations of these interactions. LC/MS/MS is a powerful tool for quantitative analysis when evaluated on the basis of speed, specificity, reliability and sensitivity. For these reasons, the present paper explored the feasibility of bonded macrocyclic glycopeptide phases for chiral LC/MS/MS quantitative analysis. Methylphenidate was used as a model compound. A rapid chiral bioanalytical method (<7.5 min) for the determination of the enantiomers of methylphenidate was developed. A lower limit of quantification (LLOQ) of 87 pg/mL was attained for the human plasma assay. This is to our knowledge the first example of enantioselective reversed-phase LC/MS/MS for methylphenidate. The chiral column was relatively cost effective and exhibited excellent performance with no separation deterioration observed after approximately 2500 injections.

Atmospheric Pressure↗
PubMed1999

Application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to the structure determination of medium and large macrocycles formed by palladium(0)-catalyzed allylation of arenesulfonamides, sulfamide, and cyanamide.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allowed the direct determination of the extent of macrocyclic and linear oligomer formation in the palladium(0)-catalyzed allylation of highly acidic and non-nucleophilic arenesulfonamides, sulfamide, and cyanamide. Palladium-containing 15-membered-ring macrocyclic compounds gave unusual [M - H](+) ions besides [M + Na](+) and [M + K](+) adducts. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

Exploring the (1 --> 3)-beta-D-glucan conformational phase diagrams to optimize the linear to macrocycle conversion of the triple-helical polysaccharide scleroglucan

The immunologically important (1 --> 6) comb-like branched (1 --> 3)-beta-D-glucans scleroglucan, schizophyllan, lentinan, and others, exist mainly as linear triple-helical structures in aqueous solution. Partial interconversion from linear to circular topology has been reported to take place following conformational transition of the triple-helical structure and subsequent regeneration of the triplex conformation. We here report on experimental data indicating that complete strand separation of the triple-helical structure is required for this interconversion. NaOH or dimethylsulfoxide was used to induce dissociation of the triplex at combinations of concentrations and temperatures shown by calorimetry to yield a conformational transition of the triplex structures. For the alkaline treatment at 55 degrees C, it is found that up to about 30% of the material readily can be converted to the cyclic topology. This fraction increased to about 60% when the subsequent annealing of the scleroglucan in aqueous solution at pH 7 was carried out at 100 degrees C. Further increase of the annealing temperature yielded a smaller relative amount of cyclic species. The data indicate that the lower molecular weight fraction of the molecular weight distributions can be converted selectively to the macrocyclic topology by conditions that do not yield complete strand separation of the whole sample. These findings add to previous reports by providing more details about how the conditions required for the linear triplex to macrocycle interconversion relate to the conformational properties of the triple-helical structure. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗
PubMed2000

Resin effects in solid phase S(n)Ar and S(n)2 macrocyclizations.

Seven different supports were compared in solid-phase S(N)Ar and S(N)2 macrocyclization reactions. Product purities were assayed for a relatively facile ring-closure process to give products 1 and 3. Some less-facile ring-closure reactions give the undesired dimeric macrocyclization by-products 2; some of these more-demanding ring closures were also examined. Finally, experiments were performed to gauge the rate of cyclizations on different resins, and some qualitative data were obtained for this.

Dimerization↗