Solid-state acid-base interactions in complexes of heterocyclic bases with dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR spectroscopy

A cancer candidate, compound 1, is a weak base with two heterocyclic basic nitrogens and five hydrogen-bonding functional groups, and is sparingly soluble in water rendering it unsuitable for pharmaceutical development. The crystalline acid-base pairs of 1, collectively termed solid acid-base complexes, provide significant increases in the solubility and bioavailability compared to the free base, 1. Three dicarboxylic acid-base complexes, sesquisuccinate 2, dimalonate 3, and dimaleate 4, show the most favorable physicochemical profiles and are studied in greater detail. The structural analyses of the three complexes using crystal structure and solid-state NMR reveal that the proton-transfer behavior in these organic acid-base complexes vary successively correlating with Delta pKa. As a result, 2 is a neutral complex, 3 is a mixed ionic and zwitterionic complex and 4 is an ionic salt. The addition of the acidic components leads to maximized hydrogen bond interactions forming extended three-dimensional networks. Although structurally similar, the packing arrangements of the three complexes are considerably different due to the presence of multiple functional groups and the flexible backbone of 1. The findings in this study provide insight into the structural characteristics of complexes involving heterocyclic bases and carboxylic acids, and demonstrate that X-ray crystallography and 15N solid-state NMR are truly complementary in elucidating hydrogen bonding interactions and the degree of proton transfer of these complexes.     

Amphiphilic and magnetic properties of a new class of cluster-bearing [L2Cu4(mu4-O)(mu2-carboxylato)4] soft materials

A general approach toward amphiphilic systems bearing multimetallic clusters and their ability to form Langmuir-Blodgett films is presented. The synthetic strategy to stabilize these clusters involves the use of a ligand (HL) containing an N(2)O-donor set and long octadecanoic chains to obtain the carboxylate-supported [L(2)Cu(4)(mu(4)-O)(mu(2)-OAc)(4)]EtOH (1) and [L(2)Cu(4)(mu(4)-O)(mu(2)-OBz)(4)] (2) in which OAc(-) and OBz(-) represent acetate (1) and benzoate (2) co-ligands. These species were thoroughly characterized and had their structures solved by X-ray crystallography. We observed that the mu-oxo Cu(4) cluster is antiferromagnetically coupled and used broken-symmetry density functional theory (DFT) calculations to describe the main superexchange pathways of the tetracopper core. We also describe the amphiphilic properties of the ligand and the cluster-containing systems by means of area versus pressure isotherms and show that these cluster-bearing species can be transferred onto solid substrates yielding homogeneous Langmuir-Blodgett films, as characterized by atomic force microscopy and contact angle measurements.     

Modeling the syn disposition of nitrogen donors at the active sites of carboxylate-bridged diiron enzymes. Enforcing dinuclearity and kinetic stability with a 1,2-diethynylbenzene-based ligand

The syn coordination of histidine residues at the active sites of several carboxylate-rich non-heme diiron enzymes has been difficult to reproduce with small molecule model compounds. In this study, ligands derived from 1,8-naphthyridine, phthalazine, and 1,2-diethynylbenzene were employed to mimic this geometric feature. The preassembled diiron(II) complex [Fe(2)(micro-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(THF)(2)] (1), where Ar(Tol)CO(2)(-) is the sterically hindered carboxylate 2,6-di(p-tolyl)benzoate, served as a convenient starting material for the preparation of iron(II) complexes, all of which were crystallographically characterized. Use of the ligand 2,7-dimethyl-1,8-naphthyridine (Me(2)-napy) afforded the mononuclear complex [Fe(O(2)CAr(Tol))(2)(Me(2)-napy)] (2), whereas dinuclear [Fe(2)(micro-DMP)(micro-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(THF)] (3) resulted when 1,4-dimethylphthalazine (DMP) was employed. The dinuclear core of compound 3 is kinetically labile, as evidenced by the formation of [Fe(O(2)CAr(Tol))(2)(vpy)(2)] (4) upon addition of 2-vinylpyridine (vpy). The diiron analogue of 4, [Fe(2)(micro-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(vpy)(2)] (5), was prepared directly from 1. When the sterically more demanding ligand 2,6-di(4-tert-butylphenyl)benzoate (Ar(4-tBuPh)CO(2)(-)) was used, mononuclear [Fe(O(2)CAr(4)(-)(tBuPh))(2)(THF)(2)] (6) and [Fe(O(2)CAr(4)(-)(tBuPh))(2)(DMP)(2)] (7) formed. The difficulty in stabilizing a dinuclear core with these simple (N)(2)-donor ligands was circumvented by preparing a family of 1,2-diethynylbenzene-based ligands, from which were readily assembled the complexes [Fe(2)(Et(2)BCQEB(Et))(micro-O(2)CAr(Tol))(3)](OTf) (15) and [Cu(2)(Et(2)BCQEB(Et))(micro-I)(2)] (16), where Et(2)BCQEB(Et) is 1,2-bis(3-ethynyl-8-carboxylatequinoline)benzene ethyl ester. The Et(2)BCQEB(Et) framework provides both structural flexibility and the desired syn nitrogen donor geometry, thus serving as a good first-generation ligand in this class.     

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

Background

Recent studies have shown that the human right-hemispheric auditory cortex is particularly sensitive to reduction in sound quality, with an increase in distortion resulting in an amplification of the auditory N1m response measured in the magnetoencephalography (MEG). Here, we examined whether this sensitivity is specific to the processing of acoustic properties of speech or whether it can be observed also in the processing of sounds with a simple spectral structure. We degraded speech stimuli (vowel /a/), complex non-speech stimuli (a composite of five sinusoidals), and sinusoidal tones by decreasing the amplitude resolution of the signal waveform. The amplitude resolution was impoverished by reducing the number of bits to represent the signal samples. Auditory evoked magnetic fields (AEFs) were measured in the left and right hemisphere of sixteen healthy subjects.

Results

We found that the AEF amplitudes increased significantly with stimulus distortion for all stimulus types, which indicates that the right-hemispheric N1m sensitivity is not related exclusively to degradation of acoustic properties of speech. In addition, the P1m and P2m responses were amplified with increasing distortion similarly in both hemispheres. The AEF latencies were not systematically affected by the distortion.

Conclusions

We propose that the increased activity of AEFs reflects cortical processing of acoustic properties common to both speech and non-speech stimuli. More specifically, the enhancement is most likely caused by spectral changes brought about by the decrease of amplitude resolution, in particular the introduction of periodic, signal-dependent distortion to the original sound. Converging evidence suggests that the observed AEF amplification could reflect cortical sensitivity to periodic sounds.     

Steric complementarity in carboxylate anion recognition

A 2,6 pyridino-linked aminocryptand acts as a good host for carboxylate anions, oxalate, malonate, acetate and lactate at low protonation levels as shown by aqueous complexation constants. With oxalate, at the hexaprotonated level of the host, the crystal structure shows formation of a dimeric unit linked by an oxalate/semioxalate short (2.474 A) H-bond. The protonated cryptand uses a cleft-binding mode in preference to the cavity-binding mode used by other aminocryptand hosts.     

Structural and electronic behavior of unprecedented five-coordinate iron(III) and gallium(III) complexes with a new phenol-rich electroactive ligand

A new asymmetric pentadentate ligand was designed to impose low symmetry to trivalent ions. Five-coordinate Fe3+ and Ga3+ complexes were investigated by crystallographic, electrochemical, and electron paramagnetic resonance methods showing enhanced redox reversibility. Calculations were performed to account for the observed trends.     

Ab initio SCF MO results for the carborane isomers 3,5-C2B6H8, 1, 7-C2B7H9, and 1,2-C2B7H9

We report the geometry-optimized total energies and bond distances for the closo-carborane isomers 3,5-C₂B₆H₈, 1,7-C₂B₇H₉, and 1,2-C₂B₇H₉ calculated by the ab initio SCF MO method using the STO -3G basis set. Relative energies are compared with those of the other carborane isomers in the 8- and 9- atom classes. These results complete the set of calculations at the same level of theory for all deltahedral carborane isomers except for those of the 11-atom class.     

The Homoleptic U(NCSe)84– Anion in (Pr4N)4U(NCSe)8·2CFCl3 and Th(NCSe)4(OP(NMe2)3)4·0.5CH3CN·0.5H2O: First Structurally Characterised Actinide Isoselenocyanates

The neutral thorium complex Th(NCSe)₄(OP(NMe₂)₃)₄ and homoleptic octa(isoselenocyanato)uranate anion U(NCSe)₈^4– in (Pr₄N)₄U(NCSe)₈·2CFCl₃ ( 1 ) were synthesised and structurally characterised. (Pr₄N)₄U(NCSe)₈·2CFCl₃ contains the U^IV anion U(NCSe)₈^4– and was characterised using IR spectroscopy and single‐crystal X‐ray diffraction. Th(NCSe)₄(OP(N(CH₃)₂)₃)₄·0.5CH₃CN·0.5H₂O ( 2 ) was characterised using IR and Raman spectroscopy, as well as ³¹P{¹H}, ¹⁵N{¹H}, ¹⁴N{¹H}, ¹³C{¹H}, ¹H and ⁷⁷Se NMR spectroscopy and structurally characterised using single‐crystal X‐ray diffraction. The U(NCSe)₈^4– anion and Th(NCSe)₄(OP(N(CH₃)₂)₃)₄·0.5CH₃CN·0.5H₂O complex are the first structurally characterised actinide‐isoselenocyanates. The crystal structures shows an approximate square antiprismatic arrangement of the ligands around the actinide(IV) atoms.     

CORRELATION OF UVC AND UVB CYTOTOXICITY WITH THE INDUCTION OF SPECIFIC PHOTOPRODUCTS IN T-LYMPHOCYTES AND FIBROBLASTS FROM NORMAL HUMAN DONORS

Abstract— By using specific monoclonal antibodies in situ and a computer-assisted image analysis system we have determined the relative induction of cyclobutane dimers, (6–4) photoproducts and Dewar isomers in human mononuclear cells and fibroblasts following irradiation with UVC, broad-spectrum UVB and narrow-spectrum UVB. The lamps produced these lesions in different proportions, with broad-spectrum UVB inducing a greater combined yield of (6–4) photoproducts and Dewar isomers per cyclobutane dimer than UVC or narrow-spectrum UVB. The relative induction ratios of (6–4) photoproducts compared to cyclobutane dimers were 0.15, 0.21 and 0.10 following irradiation with UVC, broad- or narrow-spectrum UVB, respectively. Although Dewar isomers were induced by UVC, their relative rate of formation compared to cyclobutane dimers was significantly greater after irradiation with either broad-spectrum or narrow-spectrum UVB. These values were 0.001, 0.07 and 0.07, respectively. With each lamp source, we have determined the survival of normal human T-lymphocytes and fibroblasts at fiuences, which induce equivalent yields of cyclobutane dimers, (6–4) photoproducts or (6–4) photoproducts plus Dewar isomers. Killing of fibroblasts appears to be associated with (6–4) photoproduct formation, whereas killing of T-lymphocytes seems to be mediated by combined (6–4) plus Dewar yields. These results emphasize the need to study the biological effects of UVB because cellular responses may be different from those following UVC irradiation.     

Quantum design of ionic liquids for extreme chemical inertness and a new theory of the glass transition

In many modern technologies (such as batteries and supercapacitors), there is a strong need for redox-stable ionic liquids. Experimentally, the stability of ionic liquids can be quantified by the voltage range over which electron tunneling does not occur, but so far, quantum theory has not been applied systematically to this problem. Here, we report the electrochemical reduction of a series of quaternary ammonium cations in the presence of bis(trifluoromethylsulfonyl)imide (TFSI) anions and use nonadiabatic electron transfer theory to explicate the results. We find that increasing the chain length of the alkyl groups confers improved chemical inertness at all accessible temperatures. Simultaneously, decreasing the symmetry of the quaternary ammonium cations lowers the melting points of the corresponding ionic liquids, in two cases yielding highly inert solvents at room temperature. These are called hexyltriethylammonium TFSI (HTE-TFSI) and butyltrimethylammonium TFSI (BTM-TFSI). Indeed, the latter are two of the most redox-stable solvents in the history of electrochemistry. To gain insight into their properties, very high precision electrical conductivity measurements have been carried out in the range +20 °C to +190 °C. In both cases, the data conform to the Vogel-Tammann-Fulcher (VTF) equation with “six nines” precision (R ²?>?0.999999). The critical temperature for the onset of conductivity coincides with the glass transition temperature T _g. This is compelling evidence that ionic liquids are, in fact, softened glasses. Finally, by focusing on the previously unsuspected connection between the molecular degrees of freedom of ionic liquids and their bulk conductivities, we are able to propose a new theory of the glass transition. This should have utility far beyond ionic liquids, in areas as diverse as glassy metals and polymer science.