Ditopic Complex Research Articles

Probing the Structural Determinants of Amino Acid Recognition: X-Ray Studies of Crystalline Ditopic Host-Guest Complexes of the Positively Charged Amino Acids, Arg, Lys, and His with a Cavitand Molecule.

Crystallization of tetraphosphonate cavitand Tiiii[H, CH3, CH3] in the presence of positively charged amino acids, namely arginine, lysine, or histidine, afforded host-guest complex structures. The X-ray structure determination revealed that in all three structures, the fully protonated form of the amino acid is ditopically complexed by two tetraphosphonate cavitand molecules. Guanidinium, ammonium, and imidazolium cationic groups of the amino acid side chain are hosted in the cavity of a phosphonate receptor, and are held in place by specific hydrogen bonding interactions with the P=O groups of the cavitand molecule. In all three structures, the positively charged α-ammonium groups form H-bonds with the P=O groups, and with a water molecule hosted in the cavity of a second tetraphosphonate molecule. Furthermore, water-assisted dimerization was observed for the cavitand/histidine ditopic complex. In this 4:2 supramolecular complex, a bridged water molecule is held by two carboxylic acid groups of the dimerized amino acid. The structural information obtained on the geometrical constrains necessary for the possible encapsulation of the amino acids are important for the rational design of devices for analytical and medical applications.

Selective recognition and electrochemical sensing of dopamine using a ferrocene-based heteroditopic receptor

A redox-active ferrocene-based heteroditopic receptor bearing a boronic acid (as a catechol recognition site) and a benzo-18-crown-6-ether unit (as an ammonium ion recognition site) was synthesized. A 1:1 ditopic complex with dopamine was evidenced by mass spectrometry and NMR spectroscopy. Cyclic voltammetry measurements on the receptor in the presence of a series of organic guest species demonstrated the successful electrochemical sensing of dopamine through a distinct change in the ferrocene-centred redox-couple upon complex formation.

Interplay of Lewis acidity, intramolecular O→Sn interactions and selectivity: organotin-functionalized crown ethers as ditopic hosts for sodium and potassium halides.

The increased Lewis acidity in organotin-functionalized crown ethers X3SnCH2[19]-crown-6 (5, X = I; 6, X = Br; 7, X = Cl) not only resulted in ditopic complexation of sodium/potassium halides, but also offers an excellent strategy to manipulate through intramolecular O→Sn interactions the selectivity of the crown ether moiety towards Na+/K+ depending on the solvent.

Pyridine-2,6-dicarboxamide pincer-based macrocycle: a versatile ligand for oxoanions, oxometallates, and transition metals

A tetracarboxamide-based macrocycle has shown a general aptitude for binding both anions and metal cations. Crystallographic studies indicate that in several instances quite similar structures are obtained. The macrocycle can be readily synthesised by a one-step condensation. Smaller oxoanions (sulfate, oxalate, and nitrite) bind within a folded macrocyclic cleft. Larger oxoanions and oxometallates (dihydrogen phosphate, dichromate, and perrhenate) dangle below the folded macrocycle. Smaller divalent metal ions (nickel(II) and copper(II)) form binuclear complexes with the metal ions bound within the folded macrocycle. The larger palladium(II) also forms a ditopic complex with the two pincers units, but the macrocycle lies in a more planar, non-folded conformation.

Amphiphilic Ditopic Bis-Aqua Gd-AAZTA-like Complexes Enhance Relaxivity of Lipidic MRI Nanoprobes.

Two amphiphilic mono- and dimeric GdAAZTA-like chelates composed of stable bis-aquo Gd(III) complexes (q=2) linked to one (for the monomer) or two dodecyl aliphatic chains (for the dimer) were synthesized. Both chelates showed high relaxivity when incorporated into the lipid bilayer of liposomes or after interaction with human serum albumin (HSA). The ditopic complex shows a significantly decreased internal motion relative to the monomeric complex, associated with an enhanced relaxivity (r1 ≈60 mm(-1) s(-1) , at 30 MHz and 310 K). The presence of two metal-bound water molecules in fast exchange and the restricted rotational freedom make the relaxivity of this system the highest measured for paramagnetic liposomes.

Solution and structural binding studies of phosphate with thiophene-based azamacrocycles

Two thiophene-based monocyclic receptors L1 and L2 have been studied for phosphate binding in solutions (D2O and DMSO-d6) by 1H NMR and 31P NMR titrations, and in the solid state by single crystal X-ray analysis. Results from 1H NMR titrations suggest that the ligands bind phosphate anions in a 1:2 binding mode in DMSO-d6, with the binding constants of 5.25 and 4.20 (in log K), respectively. The binding of phosphate to L1 and L2 was further supported by 31P NMR in D2O at pH=5.2. The crystal structure of the phosphate complex of L1 reveals unambiguous proof for the formation of a ditopic complex via multiple hydrogen bonds from NH⋯O and CH⋯O interactions.

MPW1PW91‐Calculated Structures, IR Spectra, and Frontier Orbitals of Benzoylmethoxythiacalix[4]arene Complexed with Alkali Metal Ions

The molecular structures of four conformers [cone (CONE), partial cone (PACO), 1,2‐alternate (12A), and 1,3‐alternate (13A)] of benzoylmethoxythiacalix[4]arene 1 and the corresponding alkali metal ion complexes were optimized by using a mPW1PW91/6‐31G(d,p) (hybrid Hartree–Fock density functional) calculation method. The 13A conformer was the most stable among the various conformers of 1 because of less steric hindrance. The total electronic and Gibbs free energies, complexation energies, and the gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) frontier orbitals of the complexes of 1 with the sodium and potassium ions were analyzed. Among the ditopic complexes, the 13A‐type 1•2Na+ complex exhibited the strongest binding efficiency. The binding efficiency of the CONE‐type 1•Na+ complex was much stronger than that of the 12A‐type 1•Na+ complex. However, the 1•K+ complexes were relatively insensitive to the conformation of host 1. The calculated binding preference of the various conformers is consistent with the empirical solution data. The infrared spectra of the conformers of 1 and their exo complexes with the alkali metal ions were calculated by mPW1PW91 and analyzed.

Dendrimeric β-cyclodextrin/Gd(III) chelate supramolecular host-guest adducts as high-relaxivity MRI probes.

We have synthesized a new macromolecular architecture, (PAMAM)-CD8 , which consists of eight β-cyclodextrin units (β-CD) attached to a generation 1 poly(amidoamine) (PAMAM) dendrimer through a disulfide bond, which can be cleaved under reducing conditions. This system shows a pronounced hosting capability towards Gd(III) chelates functionalized with hydrophobic groups, thus leading to well-defined supramolecular adducts. (1)H NMR relaxometric investigations were carried out to follow the formation of adducts with three Gd(III) chelates based on the ligand architectures of 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid (AAZTA) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) suitably functionalized with benzyl or adamantyl (Ad) pendant groups. In particular, the ditopic complex composed of two AAZTA chelating units connected to a central aromatic ring that bears an adamantyl group showed a strong affinity (ca. 10(6) M(-1)) for the CD units of the dendrimer, which is two orders of magnitude higher than toward human serum albumin (HSA). Remarkable relaxivity enhancements (i.e., up to 71% at 1 T and 25 °C) were observed upon the formation of the macromolecular host-guest adducts due to a decrease in the molecular tumbling rate and fast water-exchange. Reduction experiments and competition studies between the paramagnetic dendrimer and HSA were carried out by relaxometric techniques. The results show that the metal complexes are not displaced by the protein, thus suggesting that this novel macromolecular probe is potentially suitable for applications in vivo.

Novel Tin-Containing Crown Ether Substituted Ferrocenophanes as Redox-Active Hosts for the Ditopic Complexation of Lithium Chloride

The synthesis is reported of the crown ether substituted tin-containing ferrocenophanes fc(SiMe2CH2)2Sn(X)CH2CH(CH2OC2H4OCH2)2 (1, X = Ph; 2, X = I; 3, X = Cl; 4, X = F) and of the ditopic complex 3·LiCl. The compounds were characterized by multinuclear NMR spectroscopy, single-crystal X-ray diffraction analysis, and cyclic voltammetry. DFT calculations revealed important two-electron stabilization in 3 and 4 due to intramolecular O→Sn coordination that is absent in 2.

Intramolecularly Coordinated Bis(crown ether)-Substituted Organotin Halides as Ditopic Salt Receptors

The synthesis of the bis(crown ether)-substituted organostannanes X2Sn(CH2-[16]-crown-5)2 (3, X = I; 4, X = Br; 5, X = Cl; 6, X = F) and X2Sn(CH2-[13]-crown-4)2 (10, X = I; 11, X = Br; 12, X = F) is reported. The compounds have been characterized by 1H, 13C, 19F, and 119Sn NMR spectroscopy, elemental analyses, and electrospray ionization mass spectrometry (ESI-MS). Single-crystal X-ray diffraction analyses reveal a distorted-octahedral cis,cis,trans configuration of the tin atoms in compounds 4–6 and 10–12 as a result of intramolecular O→Sn coordination. The ability of the host molecules to form mono- and ditopic complexes with various halide salts in different solvents, including water, has been investigated by NMR spectroscopy and ESI-MS.

Orthogonal synthesis of a heterodimeric ligand for the development of the GdIII–GaIII ditopic complex as a potential pH-sensitive MRI/PET probe

A heterodimeric polyaminocarboxylate ligand based on a DO3A-sulfonamide linked to AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetracarboxylic acid) was synthesised via an orthogonal pathway in order to differentiate the two chelating cages and allow the formation of a Gd(III)-Ga(III) heteroditopic complex. The goal is to create a smart MRI/PET probe with pH dependent relaxivity and with the bimodal imaging approach that enables direct quantification of the stimulus, in this case pH. A (1)H NMR relaxometric study of the Gd-Ga heteroditopic complex addressed the pH modulation of the relaxivity and thus its possible use as an MRI pH sensitive probe.

MPW1PW91 Calculated Structures and IR Spectra of Thiacalix[4]biscrown-5 Complexed with Alkali Metal Ions

The molecular structures of thiacalix[4]biscrown-5 (1) and p-tert-butylthiacalix[4]biscrown-5 (2) and their alkali-metal-ion complexes were optimized using the DFT BLYP/6-31G(d) and mPW1PW91/6-31G(d,p) (hybrid HF-DF) calculations. The total electronic energies, the normal vibrational modes, and the Gibbs free energies of the mono- and di-topic complexes of each host with the sodium and potassium ions were analyzed. The <TEX>$K^+$</TEX>-complexes exhibited relatively stronger binding efficiencies than <TEX>$Na^+$</TEX>-complexes for both the monoand di-topic complexes of 1 and 2 comparing the efficiencies of the sodium and potassium complexes with an anisole and phenol. The mPW1PW91/6-31G(d,p) calculated distances between the oxygen atoms and the alkali metal ions were reported in the alkali-metal-ion complexes (<TEX>$1{\cdot}Na^+$</TEX>, <TEX>$1{\cdot}2Na^+$</TEX>, <TEX>$1{\cdot}K^+$</TEX>, <TEX>$1{\cdot}2K^+$</TEX>, <TEX>$2{\cdot}Na^+$</TEX>, <TEX>$2{\cdot}Na^+$</TEX>, <TEX>$2{\cdot}K^+$</TEX>, <TEX>$2{\cdot}2K^+$</TEX>). The BLYP/6-31G(d) calculated IR spectra of the host 1 and its mono-topic alkali-metal-ion complexes are compared.

Molecular Recognition with Ditopic Cavitand Re Complexes

AbstractThe synthesis of a series of cavitand receptors bearing increasing numbers of phosphonate groups at their upper rims and of the corresponding Re‐based ditopic complexes is reported. The molecular recognition properties of these phosphonate cavitands towards both monotopic and ditopic N‐methylpyridinium salts were investigated. The numbers and spatial dispositions of P=O units are pivotal for the complexation of guest ions. The removal of a single P=O bridge from the parent tetraphosphonate cavitand was sufficient to reduce the association constant by almost three orders of magnitude. Elimination of a second P=O unit completely abolished complexation in the AC distal isomer, both in monotopic and in ditopic hosts. The preorganised structure obtained by interconnection of two triphosphonate cavitands through a Re system showed moderate positive self‐assembly cooperativity in the inclusion of ditopic N‐methylpyridinium salts in both polar and nonpolar solvents. The speciation profile in ethanol indicates that the clamshell 1:1 complex is dominant at low concentrations (&lt; 10–4 M) whereas the 1:2 complex is preferred at higher concentrations of ditopic guest.

Ditopic Complexation of Selenite Anions or Calcium Cations by Pirenoxine: An Implication for Anti-Cataractogenesis

This study investigated whether and how pirenoxine (PRX) interacts with selenite or calcium ions, as these two ions have been proven respectively a factor leading to the formation of lens cataract. UV, NMR, and isothermal titration calorimetry (ITC) analysis indicated that PRX could bind maximum up to six selenite anions and the binding site preference was concentration dependent with the peripheral binding first followed by the π-π interactions with the aromatic moiety; while for calcium cation interaction the 3-carboxylate and β-ketoimine functional groups were responsible for chelating calcium ions. The results obtained by MP2/6-31+G(d) molecular orbital calculations provided theoretical evidence in support of the π-π interactions between selenite and the PRX aromatic framework, and further analysis of the binding energies with the aromatic moiety indicates that these interactions take place most likely at the benzoquinone (ring I) π-system. The calcium binding preferences with PRX were also determined based on the stabilization energy obtained by B3LYP/6-31+G(d) calculations, showing the binding preferences were site 2 > site 1 > site 3 > ring II, consistent with the experimental data. The in vitro study of the reduction of selenite or calcium ions-induced lens turbidity by PRX with ditopic recognition properties was thus demonstrated. These results may provide a rationale for using PRX as an anti-cataract agent and warrant further biological studies.

Ditopic complexes of silene H 2Si [dbnd]CH 2 with bidentate ligands Me 2NCH 2SiH nF 3-n. Structures, formation energies, AIM and ELF analyses.

Ditopic complex formation of silene H 2Si CH 2 with bidentate ligands Me 2NCH 2SiH nF 3-n ( n = 0–3) was studied at the MP4(SDQ(T)6-311G(d,p))//MP2/6-31G(d,p) levels of theory. The AIM and ELF analyses have shown that π-bonding in the silenic Si 1 C moiety in the relatively weak (H 2Si 1 CH 2)·(Me 2NCH 2Si 2 H nF 3-n) ( n = 2, 3) ditopic complexes is partially preserved.

Binding and selectivity aspects of an expanded azamacrocycle for anions.

An expanded azamacrocycle L, containing four secondary and two tertiary amines was synthesized, and its binding ability towards chloride, bromide, iodide, sulfate, nitrate and perchlorate were determined by (1)H NMR titrations in D(2)O at pH 1.7. The results suggest that the ligand is capable of forming a complex with each of the anions examined, showing the selectivity for sulfate in water. X-ray diffraction analysis of the perchlorate complex of L suggests that the ligand is tetraprotonated and is involved in interacting anions from both sides forming a ditopic complex with strong NH···O bonds. In the packing diagram, the macrocycles and external perchlorates are alternatively linked though hydrogen bonding to form a 1D chain.

Search for Novel Ditopic Complexes with Potential Cytotoxic Activity

Search for Novel Ditopic Complexes with Potential Cytotoxic Activity

A new hexaaminomacrocycle for ditopic binding of bromide

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

Organotin Compounds Ph2XSnCH2-[19]-crown-6 (X = Ph, F, Cl, Br, I, SCN) and Ph2ISnCH2Sn(I)PhCH2-[19]-crown-6 as Ditopic Receptors for Potassium Salts

The syntheses of the organotin-substituted crown ethers Ph2XSnCH2[19]-crown-6 (1, X = Ph; 2, X = Br; 3, X = I; 4, X = Cl; 5, X = F; 6, X = SCN) and Ph2XSnCH2Sn(Y)PhCH2-[19]-crown-6 (7, X = Y = Ph; 8, X = Ph, Y = I; 9, X = Y = I) and of the ditopic complexes 5·KF, 6·KSCN, and 9·KF are reported. These compounds are characterized by elemental analyses, 1H, 13C, and 119Sn NMR spectroscopies, electrospray mass spectrometry, and in the cases of 1−4, 8, 9·H2O, and 9·KF also by single-crystal X-ray diffraction studies. The coordination geometry about the tin atoms in compounds 1 and 8 (Sn2) is distorted tetrahedral, whereas it is trigonal bipyramidal for the tin atoms in compounds 2, 3, 4, 8 (Sn1), 9·H2O, and 9·KF.

Charge separation by ditopic complexation in the solid state: molecular structure of {Ph2(I)SnCH2Sn(Ph)(I)CH2-[16]-crown-5}·NaF·CH3OH

An intramolecular O-H-F hydrogen bridge involving a methanol molecule provides communication between the strongly separated sodium cation and fluoride anion in sodium fluoride that is, for the first time and despite its high lattice energy, ditopically complexed by an organotin-substituted crown ether.