Syntheses and molecular structures of 6-halogeno-pyridin-2-olate complexes with the diruthenium(2+) core

The complexes [Ru₂(CO)₅(μ-FpyO)₂]₂ (1), [Ru₂(CO)₄(μ-ClpyO)₂]₂ (2), and [Ru₂(CO)₄(μ-BrpyO)₂]₂ (3) were prepared from Ru₃(CO)₁₂ and 6-fluoro-2-hydroxypyridine (FpyOH), 6-chloro-2-hydroxypyridine (ClpyOH) and 6-bromo-2-hydroxypyridine (BrpyOH), respectively, in hot toluene. Compounds 1-3 are coordination dimers with a cyclo-RuORuO motif. By carrying out the reaction in hot methanol, the dinuclear complexes [Ru₂(CO)₄(μ-ClpyO)₂(CH₃OH)] (4) and [Ru₂(CO)₄(μ-BrpyO)₂(CH₃OH)] (5), respectively, were obtained. Treatment of 2 and 3 with triphenylphosphane provided the complexes [Ru₂(CO)₄(μ-ClpyO)₂(PPh₃)] (6) and [Ru₂(CO)₄(μ-BrpyO)₂(PPh₃)] (7), respectively. The solid-state structures of complexes 1, 2, 4, 6, and 7 were determined by single crystal X-ray diffraction. In all cases, a head-head coordination of the two 6-halopyridinolate ligands at the core was found. In all chlorine- or bromine-containing complexes, the axial coordination site at the ruthenium atom neighbored by two Cl or Br atoms remains unoccupied due to steric shielding by the halogen atom. In the fluoropyridinolate complex 1, the same coordination site is occupied by a carbonyl ligand.     

Studies of mononuclear and dinuclear complexes of dibromodimethylplatinum(IV): Preparation, characterization and crystal structures

A number of complexes of the types [PtBr₂Me₂(N^?N)] (N^?N = 4,4′-di-Me-2,2′-bpy (1); 4,4′-di-t-Bu-2,2′-bpy (2); 2,2′-bpz (3); bpym (4)) and [PtBr₂Me₂(L)₂] (L = H-pz (5); 4-Me-H-pz (6); H-idz (7); H-im (8); H-bim (9); quaz (10)) are reported. Characterization by NMR (¹H, ¹³C and ¹⁹⁵Pt), IR and EI-MS is given. In addition, crystal structures of several of these complexes are described. Furthermore, interactions within these structures including intramolecular hydrogen bonding and π-π stacking interactions are reported. The reactivity of selected mononuclear complexes was investigated and yielded two dinuclear complexes [PPh₄][(PtBrMe₂)₂(μ-Br)(μ-pz)₂] (11) and [(PtBr₂Me₂)₂(μ-bpym)] (12), respectively. The latter complex is accompanied by a solid-state structure. Finally, the thermal stability of all complexes is reported.     

New ruthenium complexes from Ru3(CO)12 and 6-Alkyl- or 6-Phenyl-2-hydroxypyridines

Trirutheniumdodecacarbonyl (Ru₃(CO)₁₂) reacts with 2-hydroxy-6-methylpyridine and with 2-hydroxy-5,6,7,8-tetrahydroquinoline in toluene to form centrosymmetric tetranuclear complexes of the type [Ru(η², μ-L)(CO)₂(μ₃-L)Ru(CO)₂]₂, where L is the respective (N,O)-pyridonate ligand (2 and 3). The structures of these complexes, which are almost insoluble in all common solvents, could be determined by single-crystal X-ray diffraction. Reaction of Ru₃(CO)₁₂ with 2-hydroxy-4,6-diphenylpyridine in methanol includes ortho-metallation at the phenyl ring, furnishing the dinuclear complex [Ru(κ²N,C-L)(CO)₂(μ-OCH₃)₂Ru(CO)₂ (κ²N,C-L)] (4), where L = (2-(6-hydroxy-4-phenylpyridin-2-yl)phenyl), according to an X-ray crystal structure determination.     

Reactivity of the N-heterocyclic carbene complexes [Ru(IMes)2(CO)HX] (X = OH, Cl) with alkynes

Treatment of the 16-electron hydroxy hydride complex [Ru(IMes)₂(CO)H(OH)] (1, IMes = 1,3-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene) with HCCR affords the alkynyl species [Ru(IMes)₂(CO)H(CCR)] (R = Ph 3, SiMe₃, 4) and [Ru(IMes)₂(CO)(CCR)₂] (R = Ph, 5). Deuterium labelling studies show that the mono-alkynyl complexes are formed via hydrogen transfer from a coordinated alkyne ligand to Ru-OH, while bis-alkynyl formation is proposed to take place through hydrogen transfer to Ru-H. Both 3 and 5 readily coordinate CO to give the corresponding dicarbonyl species 6 and 7. Addition of HCCPh to the hydride chloride precursor [Ru(IMes)₂(CO)HCl] (2) results in a different reaction pathway involving alkyne insertion into the Ru-H bond to yield the alkenyl chloride complex [Ru(IMes)₂(CO)(CHCHPh)Cl] 8. Complexes 3-8 have been structurally characterised by X-ray crystallography.     

Palladium(II) complexes of a bis-2-aminobiphenyl N-heterocyclic carbene: Synthesis, structural studies and catalytic activity

A new imidazolinium [(SIBiphen)H](BF₄) was synthesized in three steps from 2-aminobiphenyl. The reaction of the salt with Pd(OAc)₂, NaI and t-BuOK gave a dimeric Pd(II) complex [(SIBiphen)PdI₂]₂, which was analyzed by an X-ray diffraction study. The reaction of [Pd(allyl)Cl]₂, the imidazolinium salt and t-BuOK in THF at −78 °C gave the monomeric Pd complex, in which the N-heterocyclic carbene was bound to the metal centre, as confirmed by a single-crystal X-ray diffraction study. A preliminary catalytic study showed that these new systems were moderately active in the Suzuki-Miyaura coupling of aryl halides.     

Macrocyclic dinuclear gold(I) and silver(I) NHCs complexes

The ligands bis-(imidazolium) hexafluorophosphate (Himy = -C₃N₂H₃-, imidazolium; R = 1-naphthylmethylene, 1a; 9-anthracenylmethylene, 1b) with an oxoether chain were easily prepared by the reaction of substituted imidazole with the diglycol diiodide, followed by exchange of anions with . 1a and 1b reacted with Ag₂O in DMSO or CH₃CN to yield [2 + 2] dinuclear Ag(I) NHCs macrocyclic complexes 2a and 2b, which showed much different conformation in solid corresponding to the R- substituent. Carbene transmetalation reactions of 2a-b with Au(SMe₂)Cl give dinuclear Au(I) analogs 3a and 3b. The new NHCs complexes were characterized by elemental analyses, ¹H NMR, ¹³C NMR and the structures of 2a-b and 3a were confirmed by X-ray diffraction determination.     

Gold(I)-NHC complexes of antitumoral diarylimidazoles: structures, cellular uptake routes and anticancer activities

Five new heterocyclic gold carbene complexes were prepared, four chlorido-[1,3-dimethyl-4,5-diarylimidazol-2-ylidene]gold complexes 6a-d and a chlorido-[1,3-dibenzylimidazol-2-ylidene]gold complex 11, and three of them were characterised by X-ray single crystal analyses. They were tested for cytotoxicity against a panel of four human cancer cell lines and non-malignant fibroblasts, for tubulin interaction, and for the pathways of their uptake into 518A2 melanoma cells. All complexes showed cytotoxic activity in the micromolar IC₅₀ range with distinct selectivities for certain cell lines. In stark contrast to related metal-free 1-methyl-4,5-diarylimidazoles, the complexes 6 and 11 did not noticeably inhibit the polymerisation of tubulin to give microtubules. The cellular uptake of complexes 6 occurred mainly via the copper transporter (Ctr1) and the organic cation transporters (OCT-1/2). Complex 11 was accumulated preferentially via the organic cation transporters and by Na⁺/K⁺-dependent endocytosis. The new gold carbene complexes seem to operate by a mechanism different from that of the parent 1-methylimidazolium ligands.     

Reduction of diruthenium(II,III) carboxylate compounds with hydroquinone: a facile preparation of diruthenium(II) complexes

The synthesis of the diruthenium(II) compounds [Ru₂(μ-O₂CR)₄(MeOH)₂] [R = Me (1), Ph (2), CMePh₂ (3) C₆H₄-p-OMe (4), C₆H₄-p-CMe₃ (5)] by reaction of with hydroquinone, under a nitrogen atmosphere, in the presence of a base is described. This reaction constitutes an easy via to the preparation of diruthenium(II) compounds. The structure of the complexes [Ru₂(μ-O₂CMe)₄(MeOH)₂] (1) and [Ru₂(μ-O₂CPh)₄(thf)₂] (2b) is established by single crystal X-ray diffraction. These compounds show a diruthenium(II) unit bridged by four carboxylate ligands with the axial positions occupied by methanol and tetrahydrofuran molecules for 1 and 2b, respectively. Complex 1 shows, in the solid state, polymeric chains in which the molecules [Ru₂(μ-O₂CMe)₄(MeOH)₂] are linked by hydrogen bonds.     

Heterobimetallic chloro bridgedcomplexes of (η:η−C10H16)-ruthenium(IV) with palladium(II), platinum(II), rhodium(III), iridium(III), copper(I) and rhodium(I)

Metathesis of [(η³:η³−C₁₀H₁₆)Ru(Cl) (μ−Cl)]₂ (1) with [R₃P) (Cl)M(μ-Cl)]₂ (M = Pd, Pt), [Me₂NCH₂C₆H₄Pd(μ-Cl)]₂ and [(OC)₂Rh(μ-Cl)]₂ affords the heterobimetallic chloro bridged complexes (η³:η³-C₁₀H₁₆) (Cl)Ru(μ-Cl)₂M(PR₃)(Cl) (M = Pd, Pt), (η³:η³-C₁₀H₁₆) (Cl)Ru(μ-Cl)₂PdC₆H₄CH₂NMe₂ and (η³:η³-C₁₀H₁₆) (Cl)Ru(μ-Cl)₂Rh(CO)₂, respectively. Complex 1 reacts with [Cp^*M(Cl) (μ-Cl)]₂ (M = Rh, Ir), [p-cymene Ru(Cl) (μ-Cl]₂ and [(Cy₃P)Cu(μ-Cl)]₂ to give an equilibrium of the heterobimetallic complexes and of educts. The structures of (η³:η³-C₁₀H₁₆)Ru(μ-Cl)₂Pd(PR₃) (Cl) (R = Et, Bu) and of one diastereoisomer of (η³:η³-C₁₀H₁₆)Ru(μ-Cl)₂IrCp^*(Cl) were determined by X-ray diffraction.     

Complexes of the imine/thioether mixed-donor ligand 8-methylthioquinoline with d-configurated transition metal centers: synthesis, structures and comparison with complexes of 1-methyl-2-(methylthiomethyl)-1H-benzimidazole

Coordination compounds of chelating 8-methylthioquinoline (MTQ) with the complex fragments Re^I(CO)₃Cl, [Ru^II(bpy)₂]²⁺, [Rh^III(C₅Me₅)Cl]⁺, [Ir^III(C₅Me₅)Cl]⁺, and Pt^IVMe₄ were synthesized and structurally characterized. Whereas the ruthenium(II) complex displays the strongest preference of bonding to N versus S, the compound (MTQ)PtMe₄ shows the most balanced metal-donor bonding within the chelate ring due to a relatively short bond to S (2.319 Å) versus N (2.150 Å). The complex fac-(MTQ)Re(CO)₃Cl exhibits a particularly long metal-sulfur bond at 2.472 Å. Cyclic voltammetry of [(MTQ)Ru(bpy)₂](PF₆)₂ reveals one reversible oxidation to Ru^III and three closely spaced reduction waves for the coordinated ligands. In comparison with the imine/thioether chelate ligand 1-methyl-2-(methylthiomethyl)-1H-benzimidazole (mmb) the MTQ ligand with its more rigid chelate setting N(sp²)-C(sp²)-C(sp²)-S forms generally shorter M-S bonds and displays stronger π acceptor behaviour.     

Syntheses and structures of bis(2,6-xylyl-nacnac) copper(I) complexes

The copper(I) complexes {(bis-2,6-dimethylphenyl-penta-2,3-diiminato)Cu}₂(μ-toluene), 3 has been prepared and its reactivity against Lewis bases and nitrous oxide investigated. Complex 3 crystallizes as a toluene-bridged dimer and forms mono- and dinuclear benzene adducts in C₆D₆ solution. It does not coordinate excess THF, but reacts quantitatively with 1 equiv. of acetonitrile. Reaction with 2,6-xylyl isonitrile yields (bis-2,6-dimethylphenyl-penta-2,3-diiminato)Cu(2,6-xylyl isonitrile), 5, (ν_CN = 2123 cm⁻¹), which was characterized by an X-ray diffraction study. Complex 3 does not react with nitrous oxide in either C₆D₆ solution (5 days 50 °C) or in diethyl ether (13 days at ambient temperature).     

Syntheses, structures and vibrational spectroscopy of some 1:1 and 1:2 adducts of silver(I) oxyanion salts with 2,2′-bis(pyridine) chelates

Syntheses and room-temperature single-crystal X-ray structure determinations are recorded for a number of adducts of 1:1 stoichiometry of silver(I) oxyanion salts (perchlorate, nitrate, trifluoroacetate (‘tfa’) (increasing basicity)) with 2,2′-bis(pyridine) ligands (2,2′-bipyridyl, ‘bpy’; 2,2′-biquinolyl, ‘bq’; 2,2′-dipyridylketone, ‘dpk’; 2,9-dimethylphenanthroline, ‘dmp’). The adducts take two forms: (a) neutral mononuclear molecules, in which the 2,2′-bis(pyridine) ligand behaves as a chelate, with the silver coordination number dependent on the denticity of the anion; these are Agtfa:bpy (1:1) and AgClO₄:bq (1:1) (and various (ionic) acetonitrile or pyridine solvates AgClO₄:bq/dmp:MeCN/py (1:1:1), in which the solvent molecules are coordinated); and (b) one-dimensional polymers. The latter are diverse: in AgClO₄:bpy, dpk (1:1), the anion is discrete, the polymer made up of an array of two-coordinate silver atoms linked by bpy ligands twisted about their central connecting element. In AgNO₃:bpy, bq (1:1), the bpy ligands are chelating with the oxyanions bridging, cf. previously reported AgNO₃:dpk (1:1), in which the nitrate chelates the metal, with the dpk bridging, chelating N,O to one silver, while the other nitrogen bridges to the next. With Agtfa, a novel binuclear adduct has been isolated in conjunction with the hydrated ligand, Agtfa:dpk:(dpk · H₂O) (1:1:2). The far-IR spectra of several of these complexes show bands that can be assigned to the ν(AgN) modes, the positions of these bands correlating well with the relative Ag-N bond lengths.Syntheses and single-crystal X-ray structural characterizations are also reported for various adducts of silver(I) perchlorate, nitrate and trifluoromethanesulfonate with bpy, bq, ‘phen’ (= 1,10-phenanthroline), and ‘dmp’, of stoichiometry AgX:L (1:2). In each case the complex is ionic [AgL₂]X; the silver atom is four-coordinate, but diverse and remarkable variations in stereochemistries associated with changes in the interligand N-Ag-N angles, presumably influenced by the different packing arrangements, are observed.     

Unusual ruthenium hydride complexes supported by the [N(2-PPh2-4-Me-C6H3)2] pincer ligand

Complexes of Ru(II) containing the pincer ligand [⁻N(2-PPh₂-4-Me-C₆H₃)₂] (PNP^Ph) were prepared. The complex (PNP^PhH)RuCl₂ (1) was treated with 2 equiv AgOTf to produce the triflate complex (PNP^PhH)Ru(OTf)₂ (2). Complex 1 was also treated with an excess of NaBH₄ to give a bimetallic complex [(PNP^Ph)RuH₃]₂ (3). A number of methods, including X-ray crystallography, NMR spectroscopy, and computational studies, were used to probe the structure of 3. Addition of Lewis bases to 3 resulted in octahedral complexes containing a hydride ligand trans to a dihydrogen ligand.     

N-Alkylation of tripodal iron(III) imidazolate complexes: Reactivity and structure

The N-alkylation of iron(III) complexes of the tripodal imidazolate complexes derived from the Schiff base condensation of tris(2-aminoethyl)amine (tren) with three molar equivalents of 2-imidazolecarboxaldehyde (2ImH), 4-imidazolecarboxaldehyde (4ImH) or 4-methyl-5-imidazolecarboxaldehyde (5-Me4ImH) was investigated. While each complex possesses three nucleophilic imidazolate nitrogen atoms, only the complex derived from 2-imidazolecarboxaldehyde, Fetren(2Im)₃, was completely alkylated under the ambient conditions used in this work. Using methyl iodide as the alkylating agent, a correlation between spin state of the product and degree of methylation was observed. Low spin iron complexes were more nucleophilic than high spin systems. The structure reactivity relationship was exploited in the reaction of Fetren(2Im)₃ with methyl iodide and allyl iodide to give [Fetren(N-Me2Im)₃]²⁺ and [Fetren(N-allyl2Im)₃]²⁺. The products are iron(II) due to reduction of the iron(III) by iodide ion which builds up in the reaction mixture as the alkylation reaction proceeds. These complexes were characterized by a number of methods including EA, IR, ES-MS, Mössbauer spectroscopy, magnetic susceptibility and X-ray diffraction.     

Palladium(II) complexes of imidazolin-2-ylidene N-heterocyclic carbene ligands with redox-active dimethoxyphenyl or (hydro)quinonyl substituents

Four novel imidazolium salts, precursors to N-heterocyclic carbene (NHC) ligands, with 2,5-dimethoxybenzyl or 2,5-dihydroxybenzyl (i.e., p-hydroquinone) substituents have been prepared. The crystal structure of the hydroquinone-substituted imidazolium salt H₃L³Br reveals Br⁻?H-O bridged chiral chains of alternating [H₃L³]⁺ cations and Br⁻ counter-ions parallel to the x-axis. Palladium(II) complexes were accessible from reactions of the dimethoxyphenyl-substituted imidazolium precursors with palladium(II) acetate, but not from reactions of imidazolium cations with hydroquinonyl substituents. The crystal structure of the bis(dimethoxybenzyl)-substituted bis(NHC)Pd complex, cis-[PdBr₂(L²)] (2), is described. Puckering of the bis(NHC) ligand leads to a cleft in which an included molecule of dimethylformamide is situated. The cleft is closed by one of the dimethoxybenzyl groups which π-stacks with the dimethylformamide; the other dimethoxybenzyl group points away from the cleft and Pd(II) centre. Reaction of complex 2 with BBr₃ afforded the targeted bis(hydroquinone)-substituted bis(NHC)Pd(II) complex 3 (97% yield) which, in turn, was oxidised by 2,3-dichloro-5,6-dicyano-benzoquinone to the corresponding p-benzoquinone-substituted bis(NHC)Pd(II) complex 4 (98% yield). The cyclic voltammograms of the Pd(II) complexes 2-4 reveal waves that are attributed to an admix of the anticipated ligand-centred and [Pd(C-NHC)₂Br₂]-centred processes.     

Synthesis of a series of ruthenium and rhodium complexes with tridentate pyridine-based ligands containing hydrogen bonding groups

A series of ruthenium and rhodium complexes with a urea-disubstituted pyridine ligand are reported. The X-ray crystal structures of three of these species, RuCl₂(L¹)(PPh₃) (1), [Ru(MeCN)₂(L¹)(PPh₃)][BF₄]₂ (3) and Rh(CH₂Cl)Cl₂(L¹) (9) (where L¹ = N,N′-(2,2′-(1E,1′E)-(1,1′-(pyridine-2,6-diyl)bis(ethan-1-yl-1-ylidene))bis(azan-1-yl-1-ylidene)bis(ethane-2,1-diyl))diacetamide) have shown that the disubstituted pyridine acts as a tridentate ligand and its urea substituents engage in hydrogen bonding interactions with species coordinated to the metal centres. The reactivity of the ruthenium complexes towards coordination of other anions such as NCS⁻ has been investigated, as well as the oxidative-addition of alkyl chlorides to rhodium(I) centres (to yield species such as 9).     

Synthesis and structures of mono- and tetra-nuclear silver complexes of styrene-containing N-heterocyclic carbene

Two tetra-nuclear Ag(I) complexes with styrene-functionalized N-heterocyclic carbene [AgL₂]₂[Ag₂X₄] (L = 1-methyl-3-(4-vinylbenzyl)imidazol-2-ylidene, X = Cl, 2a; X = I, 2b) were prepared by the reactions between the corresponding imidazolium salts with Ag₂O. The reaction mixture was further treated with AgBF₄ to give a mononuclear ion-pair complex [AgL₂][BF₄] (3). The molecular structures of these new Ag(I) complexes have been determined by X-ray diffraction analyses. 2a and 2b consist of two [Ag(L)₂]⁺ fragments with the central [Ag₂X₄]²⁻ anion held together by the close Ag(I)-Ag(I) interactions. Complex 3 is a mononuclear ion-pair complex with a linear bi-coordinate Ag fragment.     

Syntheses and structures of mononuclear manganese(II) complexes bearing bis(1-methylimidazol-2-yl)ketone ligands

The ligand bis(1-methylimidazol-2-yl)ketone (bik) (1) was applied in the synthesis of mononuclear manganese(II) complexes. The complexes [Mn(bik)₂Cl₂] (2), [Mn(bik)₂(OH₂)Br]Br × H₂O (3b) and [Mn(bik)₃](ClO₄) (4) were characterised by X-ray crystallography, ESR and UV-Vis methods.     

Rh(I) complexes containing tris(pyrazolyl)amine and bis(pyrazolyl)amine ligands: synthesis and NMR studies

The tris(pyrazolyl)amine ligands: tris[2-(1-pyrazolyl)methyl]amine (tpma), tris [3,5-dimethyl-1-pyrazolyl)methyl]amine (tdma), tris[2-(1-pyrazolyl)ethyl]amine (tpea), tris[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (tdea) and bis(pyrazolyl)amine ligands: bis[2-(1-pyrazolyl)ethyl]amine (bpea) and bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (bdea) react with [RhCl(cod)]₂ in presence of NaBF₄ (tpma, tdma and bdea) or AgBF₄ (tpea, tdea and bpea) to lead to [Rh(cod)L] (BF₄) (L=tpma (1), tdma (2), bdea (3), tpea (4), tdea (5) and bpea (6)). These complexes have been characterised by elemental analyses, conductivity, IR, ¹H and ¹³C NMR spectroscopy and liquid mass (with electrospray) spectrometry. The ¹H NMR spectra of 1, 2 show the presence of two isomers in solution in a 3:1 ratio (coordination κ² or κ³ type) in a thermodynamic equilibrium. The steric bulk of cyclo-octa-1,5-diene causes it to prefer the κ² mode of bonding as majority. Similar to previous published results, complexes 4 and 5 exist in a sole form in solution (probably κ² isomer). Finally, the complexes 3 and 6 are fluxional. A NMR study shows that this fluxional process is not frozen at 183 K.     

Structural basis for AMPA receptor activation and ligand selectivity: crystal structures of five agonist complexes with the GluR2 ligand-binding core

Glutamate is the principal excitatory neurotransmitter within the mammalian CNS, playing an important role in many different functions in the brain such as learning and memory. In this study, a combination of molecular biology, X-ray structure determinations, as well as electrophysiology and binding experiments, has been used to increase our knowledge concerning the ionotropic glutamate receptor GluR2 at the molecular level. Five high-resolution X-ray structures of the ligand-binding domain of GluR2 (S1S2J) complexed with the three agonists (S)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid (2-Me-Tet-AMPA), (S)-2-amino-3-(3-carboxy-5-methylisoxazol-4-yl)propionic acid (ACPA), and (S)-2-amino-3-(4-bromo-3-hydroxy-isoxazol-5-yl)propionic acid (Br-HIBO), as well as of a mutant thereof (S1S2J-Y702F) in complex with ACPA and Br-HIBO, have been determined. The structures reveal that AMPA agonists with an isoxazole moiety adopt different binding modes in the receptor, dependent on the substituents of the isoxazole. Br-HIBO displays selectivity among different AMPA receptor subunits, and the design and structure determination of the S1S2J-Y702F mutant in complex with Br-HIBO and ACPA have allowed us to explain the molecular mechanism behind this selectivity and to identify key residues for ligand recognition. The agonists induce the same degree of domain closure as AMPA, except for Br-HIBO, which shows a slightly lower degree of domain closure. An excellent correlation between domain closure and efficacy has been obtained from electrophysiology experiments undertaken on non-desensitising GluR2i(Q)-L483Y receptors expressed in oocytes, providing strong evidence that receptor activation occurs as a result of domain closure. The structural results, combined with the functional studies on the full-length receptor, form a powerful platform for the design of new selective agonists.