Encapsulation of cationic ruthenium complexes into a chiral self-assembled cage

A chiral supramolecular assembly encapsulates the two cationic ruthenium sandwich complexes [CpRu(eta(6)-C(6)H(6))](+) and [CpRu(p-cymene)](+). The host-guest complexes K(11)[CpRu(eta(6)-C(6)H(6)) subset Ga(4)L(6)] (2) and K(11)[CpRu(p-cymene) subset Ga(4)L(6)] (3) were characterized by one- and two-dimensional NMR techniques as well as by electrospray mass spectrometry. Encapsulation of the prochiral complex [CpRu(p-cymene)](+) by the chiral host renders enantiotopic protons diastereotopic as evidenced by (1)H NMR spectroscopy.     

Investigation of the copper binding site on the human islet amyloid polypeptide hormone

The metal ion binding sites of human islet amyloid polypeptide (hIAPP) have been investigated to explain the biological activity difference in the fibril formation process. The structures of [hIAPP...Cu (or Al)](n+) and [hIAPP17-30...Cu]2+ complex were investigated by electrospray ionization-mass spectrometry (ESI-MS). The fragmentation patterns of [hIAPP...Cu [or Al)](n+) and [hIAPP17-30...Cu]2+ complex were analyzed by tandem mass spectrometry (MS/MS) and multi-stage mass spectrometry (MS3) spectra. The [hIAPP+Cu+H]3+, [hIAPP+Al+H]4+ and [hIAPP17-30+Cu]2+ complexes were observed in MS spectra. The Cu binding site of hIAPP is suggested to be the N22-F-G-A-I26 part for the [hIAPP+Cu+H]3+ gas-phase complex. The original hIAPP conformation was supposed to be changed by the interaction between the Cu ion and the N22-F-G-A-I26 part in the [hIAPP+Cu+H]3+ gas-phase complex.     

The complexation of two different ammonium ions with resorcarenes in protic solvent medium investigated by electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry

The complexations of two ammonium ions (guests) with two resorcarenes (hosts) were investigated using electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry. Although the two guests and the two hosts were noticeably similar, the quantity of the corresponding supramolecular complexes formed varied significantly due to the differences in host conformations and guest ability to form non-covalent interactions.     

Cucurbituril-modulated supramolecular assemblies: from cyclic oligomers to linear polymers

Employing bis(p-sulfonatocalix[4]arenes) (bisSC4A) and N',N'hexamethylenebis(1-methyl-4,4'-bipyridinium) (HBV(4+)) as monomer building blocks, the assembly morphologies can be modulated by cucurbit[n]uril (CB[n]) (n = 7, 8), achieving the interesting topological conversion from cyclic oligomers to linear polymers. The binary supramolecular assembly fabricated by HBV(4+) and bisSC4A units, forms an oligomeric structure, which was characterized by NMR spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and gel permeation chromatography (GPC) experiments. The ternary supramolecular polymer participated by CB[8] is constructed on the basis of host-guest interactions by bisSC4A and the [2]pseudorotaxane HBV(4+)@CB[8], which is characterized by means of AFM, DLS, NMR spectroscopy, thermogravimetric analysis (TGA), UV/Vis spectroscopy, and elemental analysis. CB[n] plays vital roles in rigidifying the conformation of HBV(4+), and reinforcing the host-guest inclusion of bisSC4A with HBV(4+), which prompts the formation of a linear polymer. Moreover, the CB[8]-participated ternary assembly could disassemble into the molecular loop HBV(2+)@CB[8] and free bisSC4A after reduction of HBV(4+) to HBV(2+), whereas the CB[7]-based assembly remained unchanged after the reduction. CB[8] not only controlled the topological conversion of the supramolecular assemblies, but also improved the redox-responsive assembly/disassembly property practically.     

The self-assembly of a [Ga4L6](12-) tetrahedral cluster thermodynamically driven by host-guest interactions

The guest-induced synthesis of a [Ga4L6](12-) tetrahedral metal-ligand cluster resulting from a predictive design strategy is described. Each of the six dicatecholamide ligands spans an edge of the molecular tetrahedron with four Ga(III) ions at the vertices. Small cationic species not only were found to occupy the large void volume (ca. 300-400 A(3)) inside this cluster but also are necessary thermodynamically to drive cluster assembly via formation of a host-guest complex. NMe4(+), NEt4(+), and NPr4(+) all suit this purpose, and in addition the cluster exhibits a preference in the binding of these three guests: NEt4(+) is bound 300 times more strongly than NPr4(+), which is in turn bound 4 times more strongly than NMe4(+), as determined by 1H NMR spectroscopy. The K6(NEt4)6[Ga4L6] cluster was characterized by NMR spectroscopy, high- (Fourier transform ion cyclotron resonance, FT-ICR) and low-resolution electrospray ionization (ESI) mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. The binding of the NEt4(+) guest molecule was confirmed in the solid state structure, which reveals that the molecule contains large channels in the solid state. As this result exemplifies, it is suggested that guest molecules will play an increasing role in the formation of larger, predesigned metal-ligand clusters.     

Electron capture dissociation of complexes of diacylglycerophosphocholine and divalent metal ions: Competition between charge reduction and radical induced phospholipid fragmentation

Divalent metal complexes of phosphocholines, [Metal(II)(L)(n)](2+) (where Metal=Cu(2+), Co(2+), Mg(2+), and Ca(2+), L=1,2-dihexanoyl-sn-glycero-3-phosphocholine [6:0/6:0GPCho] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [16:0/18:1GPCho] and n=2-5), were formed upon electrospray ionization mass spectrometry (ESI/MS) of 8 mM solution of phosphocholine (L) with 4 mM metal salt (Metal). The electron capture dissociation (ECD) reactions of these [Metal(II)(L)(n)](2+) complexes were examined via Fourier-transform ion-cyclotron resonance mass spectrometry. A rich and complex chemistry was observed, including charge reduction and fragmentation involving losses of a methyl radical, trimethylamine, and the acyl chains. The predominant reaction channel was dependent on the size (n) of the complex, the metal and ligand used, and the size of the acyl chain. Thus charge reduction dominates the ECD spectra of the larger phosphocholine, 16:0/18:1GPCho, but is largely absent in the smaller 6:0/6:0GPCho. For complexes of 16:0/18:1GPCho, n=4-5, fragmentation from the head group mainly occurs via loss of the methyl radical and trimethylamine. At n=3, the relative abundance of fragments due to loss of acyl chain radicals increases. The abundances of ions arising from these radical losses increase further for the n=2 complexes, thereby providing information on the composition and position of the 16:0 and 18:1 acyl groups. Thus ECD of metal complexes provides structurally useful information on the phosphocholine, including the nature of the head group, the acyl chains, and the positions of the acyl chains.     

Fluorescent and electroactive cyclic assemblies from perylene tetracarboxylic acid bisimide ligands and metal phosphane triflates

Tetraaryloxy-substituted perylene tetracarboxylic acid bisimides with one or two 4-pyridyl receptor substituents at the imide functionality were synthesized and employed in transition metal directed self-assembly with Pd(II) and Pt(II) phosphane triflates. Upon mixing of the components, quantitative formation of functional molecular square-type complexes containing four dye molecules and model complexes of a 2:1 (perylene bisimide ligand:transition metal ion) stoichiometry was observed. The isolated metallosupramolecular squares were characterized by 1H and 31P [1H] NMR spectroscopy as well as conventional electrospray ionization (ESI) and ESI-FTICR mass spectrometry, which gave evidence for the structure and the high stability of these giant cyclic dye assemblies (molecular weight (3a) 8172, Pt-Pt corner diagonal ca. 3.4 nm). Studies of the optical absorption and fluorescence properties and the electrochemistry and spectroelectrochemistry of both the perylene bisimide ligands and the perylene bisimide metal complexes show that Pt(II) coordination does not interfere with the optical and electrochemical properties of the perylene bisimide ligands; this gives squares with high fluorescence quantum yields (phiF (3a)=0.88) and three fully reversible redox couples. The latter could be unambiguously related to quantitative formation of perylene bisimide radical cations (E1/2 = +0.93 V vs. Fc/Fc+), radical anions (E1/2= - 1.01 V vs. Fc/Fc+), and dianions (E1/2 = -1.14 V vs. Fc/Fc+); these redox reactions change the charge state of the cyclic assembly from +12 to zero. In contrast, Pd(II) coordination influenced the electrochemical properties of the assembly because of an irreversible palladium reduction at E1/2= -1.15 V versus Fc/Fc+. Finally, dynamic ligand exchange processes between different metallosupramolecular assemblies were investigated by multinuclear NMR and electrospray mass spectrometry. These studies confirmed the reversible nature of the pyridine-Pt(II)/Pd(II) coordination process.     

Electrospray characterization of perrhenate systems

The electrospray negative ion mode (ESI-) mass spectrometry study of freshly prepared perrhenate in the ammonium and alkali metal (Na and K) solutions has been detailed. The cone voltage dependency of the negative ion abundance clearly indicates that the collision-activated dissociation (CAD) process in the cone-to-skimmer region is the source for both linear and non-linear cone voltage dependencies. The model also highlights that the [ReO2]- and [ReO3]- ions observed in the ESI- spectra are not present in the bulk, but are due to a dissociative collision, which strips a single oxygen atom from their precursor ions, namely [ReO3]- and [ReO4]- , respectively.     

Interaction between tetramethylcucurbit[6]uril and some pyridine derivates

Interaction between tetramethylcucurbit[6]uril (TMeQ[6], host) with hydrochloride salts of 2-phenylpridine (G1), 2-benzylpyridine (G2), and 4-benzylpyridine (G3) (guests) have been investigated by using 1H NMR spectroscopy and electronic absorption spectroscopy and theoretical calculations. The 1H NMR spectra analysis established an interaction model in which the host selectively included the phenyl moiety of the HCl salt of the above three guests, and formed inclusion complexes with a host-guest ratio of 1:1. Absorption spectrophotometric analysis allowed quantitative measurement of the stability of these host-guest inclusion complexes. Particularly, we have established a competitive interaction in which one host-guest inclusion complex pair is much more stable than another host-guest inclusion complex pair. The stability constants for the three host-guest inclusion complexes of TMeQ[6]-G1, TMeQ[6]-G2, and TMeQ[6]-G3 are approximately 2x10(6), 60.7, and 19.9 mol-1.L, respectively. To understand how subtle differences in the structure of the title guests lead to a significant difference in the stability of the corresponding host-guest inclusion complexes with the TMeQ[6], ab initio theoretical calculations have been performed, not only for the gas phase but also the solution phase (water as solvent) in all cases. The calculation results revealed that when the phenyl moiety of the three pyridine derivate guests was included, the host-guest complexation reached the minimum, and the corresponding energy differences for the formation of the title host-guest inclusion complexes are qualitatively consistent with the experimental results.     

Size matters! Fragmentation chemistry of [Cu(L)n]2+ complexes of diacylglycerophosphocholines as a function of coordination number (n = 2-7)

[Cu(L)(n)](2+) complexes of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (L = D6PC) are formed upon electrospray ionization mass spectrometry (ESI-MS) of an 8 mM solution of D6PC with 4 mM CuCl(2) in 10 mM ammonium acetate buffer, pH 6.1. The collision-induced dissociation (CID) reactions of the [Cu(L)(n)](2+) complexes were examined in a linear ion trap mass spectrometer. A rich fragmentation chemistry was observed, including: loss of a neutral ligand; intermolecular ligand-ligand S(N)2 methylation; metal ion induced ligand fragmentation via carboxylate abstraction; and phosphate abstraction. The dominant reaction channel depends on the size (n) of the complex. Thus loss of neutral ligand(s) is the sole reaction channel for n = 5-7. At n = 4, S(N)2 methylation and carboxylate abstraction start to compete with neutral ligand loss. At n = 2 the carboxylate abstraction and phosphate abstraction reactions dominate the CID spectrum. The carboxylate abstraction and phosphate abstraction reactions are likely to be driven via neighboring group pathways. PM3 calculations, carried out to compare competing neighboring pathways based on the relative stabilities of the product ions, suggest a preference for five-membered ring formation for ligand fragmentation involving both carboxylate and phosphate abstraction.     

Evaluation of chiral recognition characteristics of metal and proton complexes of di-o-benzoyl-tartaric acid dibutyl ester and L-tryptophan in the gas phase

Chiral recognition of di-o-benzoyl-tartaric acid dibutyl ester (T) was achieved in the gas phase by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. In this method two divalent transition metal cations, zinc(II) and copper(II), were used as binding metal ions, and L-tryptophan (A) was used as a chiral reference. Multimeric complexes were readily formed by electrospray ionization of a methanol:water (50:50) solution containing metal ion, L-tryptophan and T. These multimeric complexes included singly charged protonated dimeric [TAH](+), doubly charged copper(II) bound tetrameric [TACu-H](2)(2+) and doubly charged zinc(II) bound tetrameric [TAZn-H](2)(2+), together with other complexes. The mass-selected complex, i.e., [TAH](+), [TACu-H](2)(2+) and [TAZn-H](2)(2+), was used to acquire the second stage mass spectra. The chiral recognition capability of these three complexes was evaluated using the abundance ratios of daughter ion to parent ion. A high degree of chiral recognition ability was observed in [TACu-H](2)(2+) and [TAZn-H](2)(2+). It was found that the type of binding ion played an important role in the chiral recognition. Different binding ions exhibited distinctive dissociation pathways and unique chiral recognition characteristics. The present method is based not only on whole-molecule loss but also on fractional-molecule loss. In addition, the reproducibility of the chiral recognition method was confirmed by several determinations of the abundance ratios of daughter ion to parent ion with a fixed activation energy and with five different activation energies. It was also shown that this chiral recognition method can tolerate acid interference.     

Calix[4]arene-based 1,3-diconjugate of salicylyl imine having dibenzyl amine moiety (L): synthesis, characterization, receptor properties toward Fe2+, Cu2+, and Zn2+, crystal structures of its Zn2+ and Cu2+ complexes, and selective phosphate sensing by the [ZnL

A calix[4]arene conjugate bearing salicylyl imine having dibenzyl moiety (L) has been synthesized and characterized, and its ability to recognize three most important essential elements of human system, viz., iron, copper, and zinc, has been addressed by colorimetry and fluorescence techniques. L acts as a sensor for Cu(2+) and Fe(2+) by exhibiting visual color change and for Zn(2+) based on fluorescence spectroscopy. L shows a minimum detection limit of 3.96 ± 0.42 and 4.51 ± 0.53 ppm and 45 ± 4 ppb, respectively, toward Fe(2+), Cu(2+), and Zn(2+). The in situ prepared [ZnL] exhibits phosphate sensing among 14 anions studied with a detection limit of 247 ± 25 ppb. The complexes of Zn(2+), Cu(2+), and Fe(2+) of L have been synthesized and characterized by different techniques. The crystalline nature of the zinc and copper complexes and the noncrystalline nature of simple L and its iron complex have been demonstrated by powder XRD. The structures of Cu(2+) and Zn(2+) complexes have been established by single crystal XRD wherein these were found to be 1:1 monomeric and 2:2 dimeric, respectively, using N(2)O(2) as binding core. The geometries exhibited by the Zn(2+) and the Cu(2+) complexes were found to be distorted tetrahedral and distorted square planar, respectively. The iron complex of L exists in 1:1 stoichiometry as evident from the mass spectrometry and elemental analysis.     

Encapsulation of cyanometalates by a tris-macrocyclic ligand tricopper(II) complex: syntheses, structural variation, and magnetic exchange coupling pathways

The reaction of [M(CN)(6)](3-) (M = Cr(3+), Mn(3+), Fe(3+), Co(3+)) and [M(CN)(8)](4-/3-) (M = Mo(4+/5+), W(4+/5+)) with the trinuclear copper(II) complex of 1,3,5-triazine-2,4,6-triyltris[3-(1,3,5,8,12-pentaazacyclotetradecane)] ([Cu(3)(L)](6+)) leads to partially encapsulated cyanometalates. With hexacyanometalate(III) complexes, [Cu(3)(L)](6+) forms the isostructural host-guest complexes [[[Cu(3)(L)(OH(2))(2)][M(CN)(6)](2)][M(CN)(6)]][M(CN)(6)]30 H(2)O with one bridging, two partially encapsulated, and one isolated [M(CN)(6)](3-) unit. The octacyanometalates of Mo(4+/5+) and W(4+/5+) are encapsulated by two tris-macrocyclic host units. Due to the stability of the +IV oxidation state of Mo and W, only assemblies with [M(CN)(8)](4-) were obtained. The Mo(4+) and W(4+) complexes were crystallized in two different structural forms: [[Cu(3)(L)(OH(2))](2)[Mo(CN)(8)]](NO(3))(8)15 H(2)O with a structural motif that involves isolated spherical [[Cu(3)(L)(OH(2))](2)[M(CN)(8)]](8+) ions and a "string-of-pearls" type of structure [[[Cu(3)(L)](2)[M(CN)(8)]][M(CN)(8)]](NO(3))(4) 20 H(2)O, with [M(CN)(8)](4-) ions that bridge the encapsulated octacyanometalates in a two-dimensional network. The magnetic exchange coupling between the various paramagnetic centers is characterized by temperature-dependent magnetic susceptibility and field-dependent magnetization data. Exchange between the CuCu pairs in the [Cu(3)(L)](6+) "ligand" is weakly antiferromagnetic. Ferromagnetic interactions are observed in the cyanometalate assemblies with Cr(3+), exchange coupling of Mn(3+) and Fe(3+) is very small, and the octacoordinate Mo(4+) and W(4+) systems have a closed-shell ground state.     

Noncovalent Complexation of Monoamine Neurotransmitters and Related Ammonium Ions by Tetramethoxy Tetraglucosylcalix[4]arene

The noncovalent complexation of monoamine neurotransmitters and related ammonium and quaternary ammonium ions by a conformationally flexible tetramethoxy glucosylcalix[4]arene was studied by electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. The glucosylcalixarene exhibited highest binding affinity towards serotonin, norepinephrine, epinephrine, and dopamine. Structural properties of the guests, such as the number, location, and type of hydrogen bonding groups, length of the alkyl spacer between the ammonium head-group and the aromatic ring structure, and the degree of nitrogen substitution affected the complexation. Competition experiments and guest-exchange reactions indicated that the hydroxyl groups of guests participate in intermolecular hydrogen bonding with the glucocalixarene.     

1H NMR chemical shift calculations as a probe of supramolecular host-guest geometry

The self-assembled supramolecular host [Ga(4)L(6)](12-) (1; L = 1,5-bis[2,3-dihydroxybenzamido]naphthalene) can encapsulate cationic guest molecules within its hydrophobic cavity and catalyze the chemical transformations of bound guests. The cavity of host 1 is lined with aromatic naphthalene groups, which create a magnetically shielded interior environment, resulting in upfield shifted (1-3 ppm) NMR resonances for encapsulated guest molecules. Using gauge independent atomic orbital (GIAO) DFT computations, we show that (1)H NMR chemical shifts for guests encapsulated in 1 can be efficiently and accurately calculated and that valuable structural information is obtained by comparing calculated and experimental chemical shifts. The (1)H NMR chemical shift calculations are used to map the magnetic environment of the interior of 1, discriminate between different host-guest geometries, and explain the unexpected downfield chemical shift observed for a particular guest molecule interacting with host 1.     

Spectroscopy, NMR and DFT studies on molecular recognition of crown ether bridged chiral heterotrinuclear salen Zn(II) complex

A barium-containing crown ether bridged chiral heterotrinuclear salen Zn(II) complex BaZn2L(ClO4)2, where L is a folded dinuclear chiral (R,R)-salen ligand, has been synthesized and characterized by elemental analysis, 1H NMR, UV-vis, IR, circular dichroism (CD) spectra, and mass spectra. As a folded dinuclear chiral host, its recognition with achiral guests (imidazole derivatives), rigid bidentate guest (1,4-diazobicyclo[2,2,2]octane, DABCO) and chiral guests (amino acid methyl esters) was investigated by means of UV-vis spectrophotometric titration, CD spectra. The association constants of D-amino acid methyl esters are found to be higher than those of their L-enantiomer. The sandwich-type binding of BaZn2L(ClO4)2-DABCO supramolecular assembly was specially studied via 1H NMR titration and 1H ROESY. To understand the recognition on molecular level, density functional theory (DFT) calculations on B3LYP/LanL2DZ were performed on the minimal energy conformations of host, guests, and host-guest complexes. The minimal energy conformations were obtained by molecular mechanics (MM) optimization and molecular dynamics (MD) simulation. The results of single point energy, HOMO energy, and charges transfer were analyzed. The results of theoretical calculations are in good agreement with the experimental data.     

Mass spectrometic study of speciation in aluminium-fluoroquinolone solutions

Fluoroquinolones (FQLs) are synthetic antibacterial agents containing a 4-oxo-1,4-dihydroquinoline skeleton. When concomintantly administered with other drugs which may contain metal ions, particularly Al(3+) (antacids, phosphate binders, vaccines etc) they may form metal-drug complexes. Pharmacokinetic studies showed that aluminium-quinolone interactions lead to reduced bio- availability and altered activity of the drug with possible development of the toxic effects of aluminum ion. Reliable speciation in Al(3+) - quinolone systems at micromolar concentration level is needed to better understand pharmaco- and toxicokinetics of the FQLs in the presence of Al. In this work, the speciation in solutions containing Al(3+) and FQL family members (fleroxacin, moxifloxacin and ciprofloxacin) was studied by electrospray mass spectrometry (ESI-MS), ESI-MS/MS, and laser desorption ionization (LDI) MS. The dominating species identified in all the three Al(3+)-FQL solutions, at ca 30-50 μmol L(-1) total Al concentration and 2:1 to 1:3 metal-to-ligand ratio in the pH range 3.0- 6.0, were the ions related to the complexes AlL(2+), AlL(2)(+) and AlL(3)(0) (L = ligand in the monodeprotonated form). Mixed protonated and hydroxo complexes were also formed at lower and higher pH values respectively and, as expected, dimeric and polymeric species were not observed in ESI spectra. LDI measurements confirmed the existence of the mononuclear complexes found by ESI, and indicated the formation of polymeric species. The ion [2Al(3+) +5(-)](+) was identified with all three FQLs. This ionic species most probably arises from Al(2)L(2) by clustering with free ligand anions. Comparison of literature potentiometric data with mass spectral data indicated good agreement between speciation schemes. The obtained results suggest the presence of strong interaction between FQLs and Al(3+) which may be important in affecting absorption of these drugs in the gastrointestinal tract.     

Supramolecular assemblies of quaternary ammonium cations and halide anions in the gas phase: ESMS-FTICR data and computer modelling

Supramolecular aggregates of tetraalkylammonium halides (R4NX) are formed by electrospray out of acetonitrile solution. Mass spectrometry reveals 88 charged aggregates for R= Me, Et, Bu; X= Br, I, ranging up to [(Bu4N)39Br42]3- in size. With the objective of improving calculations of intermolecular energies for supramolecular aggregates of ions, calibrated semi-empirical potentials for inter-ion interactions have been developed and applied to these aggregates. The accuracy of the calculated energies is supported by the measured collisional dissociation energy of (Et4N+)4 (I-)5. Energy optimisations indicate that the probable structures have the halide ions dispersed in a matrix of cations, which, for Bu4N+, can be mutually attractive. The aggregates are structurally fluid, with multiple structures separated by 4-8 kJmol(-1). The energy calculations are entirely consistent with the observed formation of large aggregates, and of multiply charged anions. It is estimated that the cohesive energies of supramolecular assemblies of ions such as these reach about 40 kJmol(-1) per constituent ion.     

Self-assembly of supramolecular platinum complexes with bis-4-pyridyl cavitands

The design and self-assembly of six new supramolecular complexes (four triangles and two 2+2 assemblies) are described. These assemblies incorporate two new bispyridyl cavitand building blocks and were prepared in excellent yields (85-95%). The assemblies and building blocks were characterized with multinuclear NMR spectroscopy, electrospray ionization mass spectrometry, and elemental analysis. Isotopically resolved mass spectrometry along with NMR data confirms the existence of the six assemblies.