Conformational preferences driven by the C-methyl substituent in chelated o-diphenylphosphino-alpha-methyl-N,N-dimethylbenzylamine rhodium complexes

The stereochemistry of the chelate rings of a number of rhodium aminophosphine complexes is studied by NMR spectroscopy. The similarity in the variable-temperature behavior for the different compounds is consistent with them having in common highly preferred chelate ring conformations. The six-membered metallacycle of coordinated (R)-PN (PN = o-diphenylphosphino-alpha-methyl-N,N-dimethylbenzylamine) adopts a delta conformation in the solid state. NMR experiments indicate that this conformation is strongly favored in solution as well. The preferred sense of helicity is imposed by the absolute configuration of the stereogenic carbon atom on the ligand, which exerts an important steric control. The complex [Rh(TFB)((C(6)H(4)CHMeNMe(2))(2)P(C(6)H(4)CHMeNHMe(2)))](BF(4))(2).H(2)O.Me(2)CO crystallizes in the monoclinic space group P2(1) with a = 12.0548(11) A, b = 16.139(2) A, c = 12.1804(10) A, beta = 100.742(9) degrees, Z = 4.     

PtII Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

The preparation and X‐ray crystal structure analysis of {trans‐[Pt(MeNH₂)₂(9‐MeG‐N1)₂]} ? {3 K₂[Pt(CN)₄]} ? 6 H₂O ( 3 a ) (with 9‐MeG being the anion of 9‐methylguanine, 9‐MeGH) are reported. The title compound was obtained by treating [Pt(dien)(9‐MeGH‐N7)]²⁺ ( 1 ; dien=diethylenetriamine) with trans‐[Pt(MeNH₂)₂(H₂O)₂]²⁺ at pH 9.6, 60 °C, and subsequent removal of the [(dien)Pt^II] entities by treatment with an excess amount of KCN, which converts the latter to [Pt(CN)₄]^2?. Cocrystallization of K₂[Pt(CN)₄] with trans‐[Pt(MeNH₂)₂(9‐MeG‐N1)₂] is a consequence of the increase in basicity of the guanine ligand following its deprotonation and Pt coordination at N1. This increase in basicity is reflected in the pK_a values of trans‐[Pt(MeNH₂)₂(9‐MeGH‐N1)₂]²⁺ (4.4±0.1 and 3.3±0.4). The crystal structure of 3 a reveals rare (N7,O6 chelate) and unconventional (N2,C2,N3) binding patterns of K⁺ to the guaninato ligands. DFT calculations confirm that K⁺ binding to the sugar edge of guanine for a N1‐platinated guanine anion is a realistic option, thus ruling against a simple packing effect in the solid‐state structure of 3 a . The linkage isomer of 3 a , trans‐[Pt(MeNH₂)₂(9‐MeG‐N7)₂] ( 6 a ) has likewise been isolated, and its acid–base properties determined. Compound 6 a is more basic than 3 a by more than 4 log units. Binding of metal entities to the N7 positions of 9‐MeG in 3 a has been studied in detail for [(NH₃)₃Pt^II], trans‐[(NH₃)₂Pt^II], and [(en)Pd^II] (en=ethylenediamine) by using ¹H NMR spectroscopy. Without exception, binding of the second metal takes place at N7, but formation of a molecular guanine square with trans‐[(Me₂NH₂)Pt^II] cross‐linking N1 positions and trans‐[(NH₃)₂Pt^II] cross‐linking N7 positions could not be confirmed unambiguously, despite the fact that calculations are fully consistent with its existence.     

Structures and stabilities of Fe2+/3+ complexes relevant to Alzheimer's disease: an ab initio study

Iron is one of the most abundant metals found in senile plaques of post mortem patients with Alzheimer's disease. However, the interaction mode between iron ions and β-amyloid peptide as well as their precise affinity is unknown. In this study we apply ab initio computational methodology to calculate binding energies of Fe(2+/3+) with the His13-His14 sequence of Aβ, as well as other important ligands such as His6 and Tyr10. Calculations were carried out at the "MP2/6-311+G(2df,2p)"//B3LYP/6-31+G(d) level of theory and solvent effects included by the IEFPCM procedure. Several reaction paths for the binding of imidazole, phenol, and the His13-His14 fragment (modeled by N-(2-(1H-imidazol-4-yl)ethyl)-3-(1H-imidazol-4-yl)propanamide) were sequentially explored. The results show that the most stable complexes containing His13-His14 and phenolate of Tyr10 are the pentacoordinated [Fe(2+)(O-HisHis)(PhO(-))(H(2)O)](+) and [Fe(3+)(N-HisHis)(PhO(-))(H(2)O)](+) compounds and that simultaneous coordination of tyrosine and His13-His14 to Fe(2+/3+) is thermodynamically favorable in water at physiological pH. Computed Raman spectra confirm the conclusion obtained by Miura et al. ( Biochemistry 2000 , 39 , 7024 ) that tyrosine is coordinated to Fe(3+) but do not exclude coordination of imidazoles. Finally, calculations of standard reduction potentials indicate that phenol coordination reduces the redox activity of the iron/Aβ complexes.     

Cyclopalladated complexes of perylene imine: mononuclear complexes with five- or six-membered metallacycles

Mononuclear palladium complexes [Pd(C^N)L(2)] (HC^N = 3-C(20)H(11)CH=NC(6)H(4)-p-C(2)H(5)) have been prepared with Pd bound to the peri site or to the ortho site of the perylenyl fragment. These metallations correspond, respectively to six-membered (L(2) = S(2)COMe (3); acac (4); Cl, PMe(3) (5); Cl, PPh(3) (6); S(2)CNEt(2) (7)) or five-membered (L(2) = S(2)COMe (8); acac (9)) isomeric palladacyclic compounds. The X-ray structures of 3, 5, 7 and 8 show that the perylenyl fragment remains essentially flat for 3, 7 and 8 and twisted for 5. Intermolecular π-π stacking of perylenyl rings is observed only for 7. All palladium complexes exhibit fluorescence associated to the perylene fragments, with emission quantum yields (in solution at room temperature) in the range 0.01-0.12 (compared to 0.13 for the free imine), and emission lifetimes ～ 1 ns. The complexes with five-membered palladacycles show lower quantum yields than their six-membered analogs. The similarity in shape of the luminescence spectra of these metallated complexes with perylene, although red-shifted, strongly suggests a perylene-dominated intraligand π-π* emissive state, metal-perturbed by interaction of the perylene orbitals with the palladium fragment.     

Optical storage effect in a platinum orthometalated liquid crystal

Received: 24 June 1997     

Mechanistic insights into dopaminergic and serotonergic neurotransmission – concerted interactions with helices 5 and 6 drive the functional outcome

Brain functions rely on neurotransmitters that mediate communication between billions of neurons. Disruption of this communication can result in a plethora of psychiatric and neurological disorders. In this work, we combine molecular dynamics simulations, live-cell biosensor and electrophysiological assays to investigate the action of the neurotransmitter dopamine at the dopaminergic D₂ receptor (D₂R). The study of dopamine and closely related chemical probes reveals how neurotransmitter binding translates into the activation of distinct subsets of D₂R effectors (i.e.: G_i2, G_oB, G_z and β-arrestin 2). Ligand interactions with key residues in TM5 (S5.42) and TM6 (H6.55) in the D₂R binding pocket yield a dopamine-like coupling signature, whereas exclusive TM5 interaction is typically linked to preferential G protein coupling (in particular G_oB) over β-arrestin. Further experiments for serotonin receptors indicate that the reported molecular mechanism is shared by other monoaminergic neurotransmitter receptors. Ultimately, our study highlights how sequence variation in position 6.55 is used by nature to fine-tune β-arrestin recruitment and in turn receptor signaling and internalization of neurotransmitter receptors.

Neurotransmitter contacts within the receptor binding site differentially contribute to the overall functional response: transmembrane helix (TM) 5 contacts promote G protein coupling whereas concerted TM5–TM6 contacts enhance β-arrestin recruitment.     

An enumeration procedure for the assembly line balancing problem based on branching by non-decreasing idle time

In this article, we present a new exact algorithm for solving the simple assembly line balancing problem given a determined cycle time (SALBP-1). The algorithm is a station-oriented bidirectional branch-and-bound procedure based on a new enumeration strategy that explores the feasible solutions tree in a non-decreasing idle time order. The procedure uses several well-known lower bounds, dominance rules and a new logical test based on the assimilation of the feasibility problem for a given cycle time and number of stations (SALBP-F) to a maximum-flow problem.     

RhIAr/AuIAr′ Transmetalation: A Case of Group Exchange Pivoting on the Formation of M−M′ Bonds through Oxidative Insertion

By combining kinetic experiments, theoretical calculations, and microkinetic modeling, we show that Pf/Rf (C₆F₅/C₆Cl₂F₃) exchange between [AuPf(AsPh₃)] and trans‐[RhRf(CO)(AsPh₃)₂] does not occur by typical concerted Pf/Rf transmetalation via electron‐deficient double bridges. Instead, it involves asymmetric oxidative insertion of the Rh^I complex into the (Ph₃As)Au?Pf bond to produce a [(Ph₃As)Au?RhPfRf(CO)(AsPh₃)₂] intermediate, followed by isomerization and reductive elimination of [AuRf(AsPh₃)]. Interesting differences were found between the LAu?Ar asymmetric oxidative insertion and the classical oxidative addition process of H₂ to Vaska complexes.