Structural consequences of anionic host-cationic guest interactions in a supramolecular assembly.

The molecular structure of the spontaneously assembled supramolecular cluster [M(4)L(6)](n-) has been explored with different metals (M = Ga(III), Fe(III), Ti(IV)) and different encapsulated guests (NEt(4)(+), BnNMe(3)(+), Cp(2)Co(+), Cp*(2)Co(+)) by X-ray crystallography. While the identity of the metal ions at the vertices of the M(4)L(6) structure is found to have little effect on the assembly structure, encapsulated guests significantly distort the size and shape of the interior cavity of the assembly. Cations on the exterior of the assembly are found to interact with the assembly through either pi-pi, cation-pi, or CH-pi interactions. In some cases, the exterior guests interact with only one assembly, but cations with the ability to form multiple pi-pi interactions are able to interact with adjacent assemblies in the crystal lattice. The solvent accessible cavity of the assembly is modeled using the rolling probe method and found to range from 253-434 A(3), depending on the encapsulated guest. On the basis of the volume of the guest and the volume of the cavity, the packing coefficient for each host-guest complex is found to range from 0.47-0.67.

A place for thioether chemistry in cellular copper ion recognition and trafficking.

Over the last decade, cysteine thiolate ligands have been shown to be critical to the Cu(I) (cuprous) binding chemistry of many cytosolic metallochaperone and metalloregulatory proteins involved in copper physiology. More recently, the thioether group of methionine has begun to emerge as an important Cu(I) ligand for trafficking proteins in more oxidizing cellular environments.

Cu(I) recognition via cation-pi and methionine interactions in CusF.

Methionine-rich motifs have an important role in copper trafficking factors, including the CusF protein. Here we show that CusF uses a new metal recognition site wherein Cu(I) is tetragonally displaced from a Met2His ligand plane toward a conserved tryptophan. Spectroscopic studies demonstrate that both thioether ligation and strong cation-pi interactions with tryptophan stabilize metal binding. This novel active site chemistry affords mechanisms for control of adventitious metal redox and substitution chemistry.

Resolution of chiral, tetrahedral M4L6 metal-ligand hosts.

The supramolecular metal-ligand assemblies of M416 stoichiometry are chiral (M = GaIII, AlIII, InIII, FeIII, TiIV, or GeIV, H41 = N,N'-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene). The resolution process of delta delta delta delta- and lambda lambda lambda lambda-[M(4)1(6)]12- by the chiral cation S-nicotinium (S-nic+) is described for the Ga(III), Al(III), and Fe(III) assemblies, and the resolution is shown to be proton dependent. From a methanol solution of M(acac)3, H(4)1, S-nicI, and KOH, the delta delta delta delta-KH3(S-nic)7[(S-nic) subset M(4)1(6)] complexes precipitate, and the lambda lambda lambda lambda-K6(S-nic)5[(S-nic) subset M(4)1(6)] complexes subsequently can be isolated from the supernatant. Ion exchange enables the isolation of the (NEt4(+))(12), (NMe4(+))(12), and K+(12) salts of the resolved structures, which have been characterized by CD and NMR spectroscopies. Resolution can also be accomplished with 1 equiv of NEt4+ blocking the cavity interior, demonstrating that external binding sites are responsible for the difference in S-nic+ enantiomer interactions. Circular dichroism data demonstrate that the (NMe4(+))(12) and (NEt4(+))(12) salts of the resolved [Ga(4)1(6)]12- and [Al(4)1(6)]12- structures retain their chirality over extended periods of time (>20 d) at room temperature; heating the (NEt4(+))(12)[Ga(4)1(6)] assembly to 75 degrees C also had no effect on its CD spectrum. Finally, experiments with the resolved K(12)[Ga(4)1(6)] assemblies point to the role of a guest in stabilizing the resolved framework.

d-orbital effects on stereochemical non-rigidity: twisted Ti(IV) intramolecular dynamics.

The isomerization dynamics of tris-catecholate complexes have been investigated by variable-temperature NMR methods, demonstrating that the intramolecular racemization of Delta and Lambda enantiomers of d0 Ti(IV) is facile and faster than that of d10 Ga(III) and Ge(IV) analogues. Activation parameters for the racemization of K2[Ti2(3)] (H(2)2 = 2,3-dihydroxy-N,N'-diisopropylterephthalamide) were determined from line shape analysis of 1H NMR spectra [methanol-d4: deltaH++ = 47(1) kJ/mol; deltaS++ = -34(4) J/mol K; deltaG++(298) = 57(3) kJ/mol; DMF-d7: deltaH++ = 55(1) kJ/mol; deltaS++ = -16(4) J/mol K; deltaG++(298) = 59(3) kJ/mol; D2O (pD* = 8.6, 20% MeOD): deltaH++ = 48(3) kJ/mol; deltaS++ = -28(10) J/mol K; deltaG++(298) = 56(3) kJ/mol]. The study of K2[Ti4(3)] (H(2)4 = 2,3-dihydroxy-N-tert-butyl-N'-benzylterephthalamide) reveals two distinct isomerization processes: faster racemization of mer-[Ti4(3)]2- by way of a Bailar twist mechanism (D3h transition state) [T(c) approximately 242 K, methanol-d4], and a slower merright harpoon over left harpoonfac [Ti4(3)]2- isomerization by way of a Rây-Dutt mechanism (C2v transition state) [T(c) approximately 281 K, methanol-d4]. The solution behavior of the Ti(IV) complexes mirrors that reported previously for analogous Ga(III) complexes, while that of analogous Ge(IV) complexes was too inert to be detected by 1H NMR up to 400 K. These experimental findings are augmented by DFT calculations of the ML3 ground states and Bailar and Rây-Dutt transition states, which correctly predict the relative kinetic barriers of complexes of the three metal ions, in addition to faithfully reproducing the ground-state structures. Orbital calculations support the conclusion that participation of the Ti(IV) d orbitals in ligand bonding contributes to the greater stabilization of the prismatic Ti(IV) transition states.

Guest exchange dynamics in an M4L6 tetrahedral host.

Guest exchange in an M(4)L(6) supramolecular assembly was previously demonstrated to proceed through a nonrupture mechanism in which guests squeeze through apertures in the host structure and not through larger portals created by partial assembly dissociation. Focusing on the [Ga(4)L(6)](12-) assembly [L = 1,5-bis(2',3'-dihydroxybenzamido)naphthalene], the host-guest kinetic behavior of this supramolecular capsule is defined. Guest self-exchange rates at varied temperatures and pressures were measured to determine activation parameters, revealing negative DeltaS and positive DeltaV values [PEt(4)(+): DeltaH = 74(3) kJ mol(-1), DeltaS = -46(6) J mol(-1) K(-1), k(298) = 0.003 s(-)); NEt(4)(+): DeltaH = 69(2) kJ mol(-1), DeltaS = -52(5) J mol(-1) K(-1), k(298) = 0.009 s(-1); NMe(2)Pr(2)(+): DeltaH = 52(2) kJ mol(-1), DeltaS = -56(7) J mol(-1) K(-1), DeltaV = +13(1) cm(3) mol(-1), k(298) = 4.4 s(-1); NPr(4)(+): DeltaH = 42(1) kJ mol(-1), DeltaS = -102(4) J mol(-1) K(-1), DeltaV = +31(2) cm(3) mol(-1), k(298) = 1.4 s(-1)]. In PEt(4)(+) for NEt(4)(+) exchange reactions, egress of the initial guest (G1) is found to be rate determining, with increasing G1 and G2 (the displacing guest) concentrations inhibiting guest exchange. This inhibition is explained by the decreased flexibility of the host imparted by exterior, or exohedral, guest interactions by both the G1 and G2 guests. Blocking the exohedral host sites with high concentrations of the smaller NMe(4)(+) cation (a weak endohedral guest) enhances PEt(4)(+) for NEt(4)(+) guest exchange rates. Finally, guest displacement reactions also demonstrate the sensitivity of guest exchange to thermodynamic endohedral guest binding affinities. When the initial guest (G1) has a weaker affinity for the host, G2 concentration dependence is observed in addition to dependence on the G2 binding strength.

The big squeeze: guest exchange in an M4L6 supramolecular host.

Guest exchange in an M4L6 supramolecular host has been evaluated to determine whether host rupture is required for guest ingress and egress. Two mechanistic models were evaluated: one requiring partial dissociation of the host structure to create a portal for guest passage and one necessitating deformation of the host structure to create a dilated aperture for guest passage without host rupture. Three related lines of inquiry support the nondissociative guest exchange mechanism. (a) Equally facile guest exchange is observed in labile ([Ga4L6]12-) and inert ([Ti4L6]8- and [Ge4L6]8-) hosts. (b) Molecular mechanics calculations demonstrate that the structural deformations required for enlargement of an M4L6 aperture in a nonrupture or nondissociative guest exchange mechanism are plausible. (c) As predicted by the calculations, CoCp*2+, a sterically demanding guest, significantly inhibits guest exchange. These results bring new insight to the application of the M4L6 supramolecular host for encapsulated reaction chemistry for which there are now several examples.

Self-assembly of tetrahedral and trigonal antiprismatic clusters [Fe4(L4)4] and [Fe6(L5)6] on the basis of trigonal tris-bidentate chelators.

In a one-pot reaction, the tetranuclear iron chelate complex [Fe4(L4)4] 6 was generated from benzene-1,3,5-tricarboxylic acid trichloride (4), bis-tert-butyl malonate (5a), methyllithium, and iron(II) dichloride under aerobic conditions. Alternatively, hexanuclear iron chelate complex [Fe(L5)6] 7 was formed starting from bis-para-tolyl malonate (5b) by employing identical reaction conditions to those applied for the synthesis of 6. The clusters 6 and 7 are present as racemic mixtures of homoconfigurational (delta,delta,delta,delta)/(lambda,lambda,lambda,lambda)-fac or (delta,delta,delta,delta,delta,delta)/(lambda,lambda,lambda,lambda,lambda,lambda)-fac stereoisomers. The structures of 6 and 7 were unequivocally resolved by single-crystal X-ray analyses. The all-iron(III) character of 6 and 7 was determined by Mössbauer spectroscopy.