Magnetization Slow Dynamics in Ferrocenium Complexes.

The single-molecule magnet (SMM) properties of a series of ferrocenium complexes, [Fe(η5 -C5 R5 )2 ]+ (R=Me, Bn), are reported. In the presence of an applied dc field, the slow dynamics of the magnetization in [Fe(η5 -C5 Me5 )2 ]BArF are revealed. Multireference quantum mechanical calculations show a large energy difference between the ground and first excited states, excluding the commonly invoked, thermally activated (Orbach-like) mechanism of relaxation. In contrast, a detailed analysis of the relaxation time highlights that both direct and Raman processes are responsible for the SMM properties. Similarly, the bulky ferrocenium complexes, [Fe(η5 -C5 Bn5 )2 ]BF4 and [Fe(η5 -C5 Bn5 )2 ]PF6 , also exhibit magnetization slow dynamics, however an additional relaxation process is clearly detected for these analogous systems.

Evidence for Reagent-Induced Spin-State Switching in Tripodal Fe(II) Iminopyridine Complexes.

We present evidence of a spin-state change that accompanies desilylation reactions performed on two related Fe(II) iminopyridine coordination complexes. To probe these systems, we performed titrations with CsF in solution and analyzed the speciation with in situ magnetometry, electrochemistry, and mass spectrometry techniques. We find that pendant tert-butyldimethylsilyl groups are readily cleaved under these conditions, and the resulting desilylated complexes exhibit overall decreased solution magnetic susceptibility values. Density functional theory and ab initio computations probe the impact of substituent identity (prior to- and post-desilylation) on the metal-ligand σ-donor and π-acceptor bonding properties. We attribute the observed spin-state changes to the decrease in entropy associated with the conformational freedom of the silylated high-spin complex, resulting in a more favored low-spin state upon desilylation.

Anionic guest-dependent slow magnetic relaxation in Co(ii) tripodal iminopyridine complexes.

We report the syntheses and magnetic property characterizations of four mononuclear cobalt(ii) complex salts featuring a tripodal iminopyridine ligand with external anion receptor groups, [CoL5-ONHtBu]X2 (X = Cl (1), Br (2), I (3) and ClO4 (4)). While all four salts exhibit anion binding through pendant amide moieties, only in the case of 1 is field-induced slow relaxation of magnetisation observed, whereas in the other salts this phenomenon is absent at the limits of our instrumentation. The effect of chloride inducing a seventh Co-N interaction and concomitant structural distortion is hypothesized as the origin of the observed dynamic magnetic properties observed in 1. Ab initio computational studies carried out on a 7-coordinate Co(ii) model species survey the complex interplay of coordination number and trigonal twisting on the sign and magnitude of the axial anisotropy parameter (D), and identify structural features whose distortions can trigger large switches in the sign and magnitude of magnetic anisotropy.

High throughput detection of deamidation using S-(5'-adenosyl)-l-homocysteine hydrolase and a fluorogenic reagent.

Deamidation of asparagine (Asn) residues is one of the most common chemical degradation pathways observed in proteins. This reaction must be understood and controlled in therapeutic drug candidates, as chemical changes can affect their efficacy and safety. The analytical tools available for detection of deamidation reaction products, such as isoaspartic acid residues, are either chromatographic or electrophoretic, and require MS detection for absolute identification of peaks. High-throughput measurement of protein degradation has typically been limited to probing the target's physical state using spectroscopic techniques. Here, we describe a high throughput assay for isoaspartate residues using fluorescent detection in a microtiter plate format. The method allows for fast detection of protein deamidation in a cost-efficient manner. The method can be employed even if the target peptide or protein contains free Cys residues. The technique appears to be selective, linear, and accurate.

Quasi-1D chains of dinickel lantern complexes and their magnetic properties.

Four new quasi-1D Ni2-lantern chain complexes of the form [Ni2(SOCR)4(L)]∞ (R = Ph, L = DABCO (1); R = Ph, L = pyz (2); R = CH3, L = DABCO (3); R = CH3, L = pyz (4)) were prepared from the reaction of [Ni2(SOCR)4(EtOH)], R = CH3 or Ph, with the N,N'-donor bridging ligands pyrazine (pyz) or 1,4-diazabicyclo[2.2.2]octane (DABCO). Reaction of [Ni2(tba)4(EtOH)], (tba = thiobenzoate) with the mono-N donor ligand quinuclidine (quin) gave the discrete Ni2-lantern complex [Ni2(tba)4(quin)] (5), whereas reaction with pyridine led to fragmentation of the lantern and formation of the known [Ni(tba)2(py)2] (6). Single-crystal X-ray diffraction reveals 2-4 to be 1D chain complexes comprising DABCO or pyz ligands which bridge the Ni2-lantern units. Complex 5 forms dimers through two equivalent NiS interactions. The Ni-Ni distances within the Ni2-lanterns are 2.5316(18)-2.595(2) Å for the 1D chain complexes 2-4, and 2.5746(4) Å in the dimeric complex 5, respectively. Comparing the solid state magnetism of 5 to precursor [Ni2(tba)4(EtOH)] demonstrates a change in coupling upon change of capping ligand. Meanwhile, chains 1-4 exhibit magnetic properties consistent with an S = 1 system, due to a mixed valent system where the two Ni centers differ in spin state, while 5 possesses two S = 1 Ni(ii) centers. DFT calculations confirm low-spin S = 0 {NiS4} and high-spin S = 1 {NiO4} centers in each lantern. Fits to the magnetic susceptibility data of the chains suggest a weak antiferromagnetic mean field interaction is present that is largely 1-D in nature, though neither pyrazine nor DABCO promote significant magnetic interaction between neighboring Ni2-lanterns.

Toward steric control of guest binding modality: a cationic Co(ii) complex exhibiting cation binding and zero-field relaxation.

We present the syntheses and characterization of several salts of a trigonal prismatic cobalt(ii) complex with a 1,3,5-triaminocyclohexane (tach)-derived ditopic ligand. The air- and moisture-stable tetraphenylborate salt (2) shows slow magnetic relaxation under both zero and applied dc fields. This complex also exhibits an unexpected ability to interact with a cationic sodium guest ion, highlighting the ambifunctional binding nature of amide groups within an iminopyridine scaffold.

Platinum-Catalyzed α,ß-Unsaturated Carbene Formation in the Formal Syntheses of Frondosin B and Liphagal.

Formal syntheses of tetracyclic terpenoids frondosin B and liphagal are described. Both synthetic routes rely on the use of platinum-catalyzed α,ß-unsaturated carbene formation for the key C-C bond forming transformations. The successful route toward frondosin B utilizes a formal (4 + 3) cycloaddition, while the liphagal synthesis features the vinylogous addition of an enol nucleophile as a key step. Both synthetic routes are discussed, revealing insights into structural requirements in the catalytic α,ß-unsaturated carbene reaction manifold.

Lewis Acid Mediated Vinylogous Additions of Enol Nucleophiles into an α,ß-Unsaturated Platinum Carbene.

A variety of substituted indoles and benzofurans are accessed via a platinum catalyzed annulation and vinylogous addition of enol nucleophiles. Several ß-dicarbonyl compounds participate in the reaction, as do α-nitro and α-cyano carbonyl species. Subjecting the indole products to acidic conditions results in the formation of fused heterocycles.

IMPROVED SYNTHESIS OF 10-(2-ALKYLAMINO-2-OXOETHYL)-1,4,7,10-TETRAAZACYCLODODECANE-1,4,7-TRIACETIC ACID DERIVATIVES BEARING ACID-SENSITIVE LINKERS.

Alkylation of the hydrobromide salts of 1,4,7-tris(methoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane and 1,4,7-tris(ethoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane with appropriate α-bromoacetamides, followed by hydrolysis, provides convenient access to 10-(2-alkylamino-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid derivatives that contain acid-sensitive functional groups. The utility of the method is demonstrated by improved syntheses of two known DOTA monoamides bearing acid-sensitive ω-tritylthio alkyl chains in much higher yields based on cyclen as the starting material.

Redox-active magnetic resonance imaging contrast agents: studies with thiol-bearing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid derivatives.

The synthesis and structure-activity relationships of a homologous series of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid gadolinium(III) complexes bearing thiol-terminated alkyl side chains from three to nine carbons in length are reported. The observed binding with human serum albumin (HSA) of the compounds having C-3 through C-7 side chain lengths was inhibited by homocysteine in a manner consistent with single-site binding. The observed binding with HSA of the compounds having C-8 and C-9 side chain lengths was only partly inhibited by homocysteine, consistent with multisite binding. The binding affinity of the C-7 compound could be related to the HSA oxidation state. 2D 1H-1H NMR TOCSY provided evidence of covalent binding of the europium analog of the C-6 compound to HSA-Cys34. The longitudinal water-proton MRI relaxivities of the gadolinium complexes at 7 T increased upon binding to HSA. On the basis of these results, the C-6 and C-7 compounds were identified as promising redox-sensitive MRI contrast agents.