The software defined implantable modular platform (STELLA) for preclinical deep brain stimulation research in rodents.

Context.Long-term deep brain stimulation (DBS) studies in rodents are of crucial importance for research progress in this field. However, most stimulation devices require jackets or large head-mounted systems which severely affect mobility and general welfare influencing animals' behavior.Objective.To develop a preclinical neurostimulation implant system for long-term DBS research in small animal models.Approach.We propose a low-cost dual-channel DBS implant called software defined implantable platform (STELLA) with a printed circuit board size of Ø13 × 3.3 mm, weight of 0.6 g and current consumption of 7.6µA/3.1 V combined with an epoxy resin-based encapsulation method.Main results.STELLA delivers charge-balanced and configurable current pulses with widely used commercial electrodes. Whilein vitrostudies demonstrate at least 12 weeks of error-free stimulation using a CR1225 battery, our calculations predict a battery lifetime of up to 3 years using a CR2032. Exemplary application for DBS of the subthalamic nucleus in adult rats demonstrates that fully-implanted STELLA neurostimulators are very well-tolerated over 42 days without relevant stress after the early postoperative phase resulting in normal animal behavior. Encapsulation, external control and monitoring of function proved to be feasible. Stimulation with standard parameters elicited c-Fos expression by subthalamic neurons demonstrating biologically active function of STELLA.Significance.We developed a fully implantable, scalable and reliable DBS device that meets the urgent need for reverse translational research on DBS in freely moving rodent disease models including sensitive behavioral experiments. We thus add an important technology for animal research according to 'The Principle of Humane Experimental Technique'-replacement, reduction and refinement (3R). All hardware, software and additional materials are available under an open source license.

Pseudohalogen Chemistry in Ionic Liquids with Non-innocent Cations and Anions.

Within the second funding period of the SPP 1708 "Material Synthesis near Room Temperature",which started in 2017, we were able to synthesize novel anionic species utilizing Ionic Liquids (ILs) both, as reaction media and reactant. ILs, bearing the decomposable and non-innocent methyl carbonate anion [CO3 Me]- , served as starting material and enabled facile access to pseudohalide salts by reaction with Me3 Si-X (X=CN, N3 , OCN, SCN). Starting with the synthesized Room temperature Ionic Liquid (RT-IL) [nBu3 MeN][B(OMe)3 (CN)], we were able to crystallize the double salt [nBu3 MeN]2 [B(OMe)3 (CN)](CN). Furthermore, we studied the reaction of [WCC]SCN and [WCC]CN (WCC=weakly coordinating cation) with their corresponding protic acids HX (X=SCN, CN), which resulted in formation of [H(NCS)2 ]- and the temperature labile solvate anions [CN(HCN)n ]- (n=2, 3). In addition, the highly labile anionic HCN solvates were obtained from [PPN]X ([PPN]=µ-nitridobis(triphenylphosphonium), X=N3 , OCN, SCN and OCP) and HCN. Crystals of [PPN][X(HCN)3 ] (X=N3 , OCN) and [PPN][SCN(HCN)2 ] were obtained when the crystallization was carried out at low temperatures. Interestingly, reaction of [PPN]OCP with HCN was noticed, which led to the formation of [P(CN)2 ]- , crystallizing as HCN disolvate [PPN][P(CN⋅HCN)2 ]. Furthermore, we were able to isolate the novel cyanido(halido) silicate dianions of the type [SiCl0.78 (CN)5.22 ]2- and [SiF(CN)5 ]2- and the hexa-substituted [Si(CN)6 ]2- by temperature controlled halide/cyanide exchange reactions. By facile neutralization reactions with the non-innocent cation of [Et3 HN]2 [Si(CN)6 ] with MOH (M=Li, K), Li2 [Si(CN)6 ] ⋅ 2 H2 O and K2 [Si(CN)6 ] were obtained, which form three dimensional coordination polymers. From salt metathesis processes of M2 [Si(CN)6 ] with different imidazolium bromides, we were able to isolate new imidazolium salts and the ionic liquid [BMIm]2 [Si(CN)6 ]. When reacting [Mes(nBu)Im]2 [Si(CN)6 ] with an excess of the strong Lewis acid B(C6 F5 )3 , the voluminous adduct anion {Si[CN⋅B(C6 F5 )3 ]6 }2- was obtained.

Pseudohalide HCN aggregate ions: [N3(HCN)3]-, [OCN(HCN)3]-, [SCN(HCN)2]- and [P(CN·HCN)2]- .

In the presence of µ-nitridobis(triphenylphosphonium) cation, [PPN]+, it was possible to stabilize and isolate [PPN]+-salts bearing the highly labile hydrogen cyanide aggregate anions of pseudohalides X (X = N3, OCN and SCN). From a concentrated solution of the [PPN]X salts in HCN, crystals of [PPN][X(HCN)3] (X = N3, OCN) or [PPN][SCN(HCN)2] could be obtained, when the crystallization was carried out fast and at low temperatures. The reaction of liquid HCN with the PCO- salt led to formation of dicyanophosphide, which crystallized as HCN disolvate [P(CN·HCN)2]-. All synthesized salts with hydrogen-bridged pseudohalide solvate anions are thermally unstable. Immediate loss of HCN was observed in the crystals outside the HCN solution. Oligomerization begins at ambient temperature, even in HCN solution. All discussed species were characterized by means of Raman spectroscopy, single crystal X-ray analysis and quantum-chemical calculations.

Salts of HCN-Cyanide Aggregates: [CN(HCN)2 ]- and [CN(HCN)3 ].

Although pure hydrogen cyanide can spontaneously polymerize or even explode, when initiated by small amounts of bases (e.g. CN- ), the reaction of liquid HCN with [WCC]CN (WCC=weakly coordinating cation=Ph4 P, Ph3 PNPPh3 =PNP) was investigated. Depending on the cation, it was possible to extract salts containing the formal dihydrogen tricyanide [CN(HCN)2 ]- and trihydrogen tetracyanide ions [CN(HCN)3 ]- from liquid HCN when a fast crystallization was carried out at low temperatures. X-ray structure elucidation revealed hydrogen-bridged linear [CN(HCN)2 ]- and Y-shaped [CN(HCN)3 ]- molecular ions in the crystal. Both anions can be considered members of highly labile cyanide-HCN solvates of the type [CN(HCN)n ]- (n=1, 2, 3 …) as well as formal polypseudohalide ions.

Heavy Neutral and Anionic Pnictogen Thiocyanates.

When [PPN]SCN (1; PPN = [Ph3P-N-PPh3]) is treated with Me3Si-SCN in methanol, [PPN][H(NCS)2] (2), a hydrogen diisothiocyanate salt bearing the [H(NCS)2]- anion, was generated, isolated, and fully characterized. Pure heavy E(NCS)3 [E = Sb (3), Bi (4)] species were obtained from the reaction of EF3 and an excess of Me3Si-SCN, while the tetrahydrofuran (THF) solvates E(NCS)3·THF were isolated when the product was recrystallized from THF. When 2 equiv of 1 was combined with Me3Si-SCN and SbF3, [PPN]2[Sb(NCS)5] (5) could be isolated. When 1 was added to BiF3, [PPN]2[Bi(NCS)3(SCN)2·THF] (6·THF), containing three SCN- ions coordinating via the N atom and two coordinating via the S atom, was isolated after recrystallization from THF. The structures of 1, 2, 3·THF, 4·THF, 5, and 6·THF were determined. 3·THF displayed a typical [3 + 3] coordination mode with a trigonal-pyramidal environment in the first coordination sphere of the Sb3+ ion, and the dianion of 5, [Sb(NCS)5]2-, featured a classical square-pyramidal molecular geometry around the Sb3+ ion with one additional Menshutkin-type interaction to one aryl ring of the [PPN]+ cation. 4·THF exhibited a distorted pentagonal-bipyramidal structure within a two-dimensional network, while in 6·THF, an octahedrally surrounded Bi3+ ion was observed.

Cyanidosilicates-Synthesis and Structure.

Starting from fluoridosilicate precursors in neat cyanotrimethylsilane, Me3 Si-CN, a series of different ammonium salts [R3 NMe]+ (R=Et, n Pr, n Bu) with the novel [SiF(CN)5 ]2- and [Si(CN)6 ]2- dianions was synthesized in facile, temperature controlled F- /CN- exchange reactions. Utilizing decomposable, non-innocent cations, such as [R3 NH]+ , it was possible to generate metal salts of the type M2 [Si(CN)6 ] (M+ =Li+ , K+ ) via neutralization reactions with the corresponding metal hydroxides. The ionic liquid [BMIm]2 [Si(CN)6 ] (m.p.=72 °C, BMIm=1-butyl-3-methylimidazolium) was obtained by a salt metathesis reaction. All the synthesized salts could be isolated in good yields and were fully characterized.

Arsenic-Mediated C-C Coupling of Cyanides Leading to Cyanido Arsazolide [AsC4 N4 ].

The chemistry of arsenic cyanides has been investigated and is found to be completely different to the chemistry of the heavier analogs antimony and bismuth as well as phosphorus. The reaction of As(CN)3 with cyanide salts resulted in the formation of an unknown cyanido arsazolide heterocycle, which represents a structure isomer of the desired [As(CN)4 ]- . The structure, bonding, and formation of this unusual heterocycle is discussed featuring an arsenic mediated C-C coupling of cyanides. [AsC4 N4 ]- salts with different counterions such as [PPh4 ]+ , [PPN]+ =[Ph3 P-N-PPh3 ]+ , Ag+ , and [BMIm]+ are reported with [BMIm][AsC4 N4 ] being a low-temperature ionic liquid (Tm =-62 °C).

Cyanido Antimonate(III) and Bismuthate(III) Anions.

The reaction of in situ generated E(CN)3 (E = Sb, Bi) with different amounts of [Ph4P]CN and [PPN]CN ([PPN]+ = [Ph3P-N-PPh3]+) was studied, affording salts bearing the novel ions [E(CN)5]2-, [Bi2(CN)11]5-, and [Bi(CN)6]3-. The valence lone pair of electrons on the central atom of antimony and bismuth(III) compounds can be either sterically active in an unsymmetric fashion (three shorter bonds + x longer bonds) or symmetric (with rather long averaged bonds). In the presence of weakly coordinating cations (e.g., [Ph4P]+ and [PPN]+), the solid-state structures of salts with [E(CN)5]2- anions contain well-separated cations and monomeric anions, which display a sterically active lone pair and a monomeric square-based pyramidal (pseudo-octahedral) structure. The [Bi(CN)5·MeCN]2- acetonitrile adduct ion exhibits a strongly distorted octahedral structure, which is better understood as a [5 + 1] coordination. The intriguing [Ph4P]6[Bi2(CN)11]CN salt consists of separated cations and anions as well as well-separated [Bi2(CN)11]5- and CN- ions. The structure of the molecular [Bi2(CN)11]5- ion can be described as two square-based-pyramidal [Bi(CN)5]2- fragments connected by a disordered bridging CN- ion, thereby leading to a distorted-octahedral environment around the two Bi centers. Here the steric effect of the lone pair is much less pronounced but still present.

Molecular E(CN)3 (E=Sb, Bi) Species Synthesized from Ionic Liquids as Solvates.

The heavy pnictogen tricyanides, E(CN)3 (E=Sb, Bi), were synthesized from EF3 and Me3 SiCN in ionic liquids, for example, 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIm][OTf]), which prevents the oligomerization of the molecular E(CN)3 species by formation of [BMIm][E(CN)3 (OTf)] salts in solution. Recrystallization of [BMIm][E(CN)3 (OTf)] from THF led to the isolation and full characterization of the molecular species E(CN)3 ⋅2 THF.

Lewis Acid Catalyzed Synthesis of Cyanidophosphates.

Salts containing new cyanido(fluorido)phosphate anions of the general formula [PF6-n(CN)n](-) (n=1-4) were synthesized by a very mild Lewis-acid-catalyzed synthetic protocol and fully characterized. All [PF6-n(CN)n](-) (n=1-4) salts could be isolated on a preparative scale. It was also possible to detect the [PF(CN)5](-) but not the [P(CN)6](-) anion. The best results with respect to purity, yield, and low cost were obtained when the F(-)/CN(-) substitution reactions were carried out in ionic liquids.

Tetracyanido(difluorido)phosphates M(+) [PF2 (CN)4 ](.).

The systematic study of the reaction of M[PF6 ] salts and Me3 SiCN led to a synthetic method for the synthesis and isolation of a series of salts containing the unprecedented [PF2 (CN)4 ](-) ion in good yields. The reaction temperature, pressure, and stoichiometry were optimized. The crystal structures of M[PF2 (CN)4 ] (M=[nBu4 N](+) , Ag(+) , K(+) , Li(+) , H5 O2 (+) ) were determined. X-ray crystallography showed the exclusive formation of the cis isomer in accord with (31) P and (19) F solution NMR spectroscopy data. Starting with the K[PF2 (CN)4 ] the room temperature ionic liquid EMIm[PF2 (CN)4 ] was prepared exhibiting a rather low viscosity.

Molecular relaxation processes in a MOF-5 structure revealed by broadband dielectric spectroscopy: signature of phenylene ring fluctuations.

The molecular mobility of a MOF-5 metal-organic framework was investigated by broadband dielectric spectroscopy. Three relaxation processes were revealed. The temperature dependence of their relaxation rates follows an Arrhenius law. The process observed at lower temperatures is attributed to bending fluctuations of the edges of the cages involving the Zn-O clusters. The processes ("region II") at higher temperatures were assigned to fluctuations of phenyl rings in agreement with the NMR data found by Gould et al. (J. Am. Chem. Soc. 2008, 130, 3246). The carboxylate groups might also be involved. The rotational fluctuations of the phenyl rings leading to the low frequency part of relaxation region II might be hindered either by some solvent molecules entrapped in the cages or by an interpenetrated structure and have a broad distribution of activation energies. The high frequency part of region II corresponds nearly to a Debye-like process: This is explained by a well-defined structure of empty pores.