Janice M. Rubin-Preminger

Bio: Janice M. Rubin-Preminger is an academic researcher from RWTH Aachen University. The author has contributed to research in topics: Hydrogen bond & Denticity. The author has an hindex of 2, co-authored 3 publications receiving 21 citations.

3,4‐Diamino­pyridine

Abstract: The amino group in the 3 position of the title compound, C5H7N3, is significantly displaced out of the plane of the heteroaromatic ring. Hydrogen bonds between the amino groups and the pyridine N atom link neighbouring mol­ecules into chains along the crystallographic c axis in a similar manner to that in 4-amino­pyridine. Additional hydrogen bonds lead to the formation of a three-dimensional network.

trans‐Aqua­bis(glyoximato‐κ2N,N′)nitro­cobalt(III)

Abstract: The molecule of the title compound, [Co(C2H3N2O2)2(NO2)(H2O)], is located on a twofold crystallographic twofold rotation axis, with the metal in a pseudo-octa­hedral coordination, the bond between Co and the aqua ligand being the longest. In addition to the two intra­molecular hydrogen bonds between the equatorial bidentate glyoximate ligands, two pairs of inter­molecular hydrogen bonds to two adjacent mol­ecules are formed.

Aquabis(dimethylyglyoximato-κ2N,N′)nitrocobalt(III) monohydrate

Abstract: The title compound, [Co(C4H7N2O2)2(NO2)(H2O)]·H2O, is a distorted octa­hedral CoIII complex with two dimethyl­glyoximate ligands in the equatorial plane and nitro and aqua substituents in the axial positions. The two dimethyl­glyoximate ligands are involved in intra­molecular hydrogen bonds. Coordinated and uncoordinated water mol­ecules participate in O—H⋯O hydrogen bonds, linking the cobalt complexes into a three-dimensional network.

3,4-diaminopyridine for the treatment of Lambert-Eaton myasthenic syndrome

Abstract: The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which antibodies against voltage-gated calcium channels inhibit cholinergic neurotransmission. LEMS is clinically characterized by muscle weakness and autonomic dysfunction. 3,4-diaminopyridine (3,4-DAP) blocks potassium channels in nerve terminals, resulting in an increase in acetylcholine release. This article describes the four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS. All trials demonstrated a significant effect on muscle strength and compound muscle action potential amplitude. Furthermore, the safety and tolerability of 3,4-DAP are reviewed. The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. Given the efficacy and safety of 3,4-DAP in LEMS, this drug is the mainstay for symptomatic treatment of LEMS.

New acentric materials constructed from aminopyridines and 4-nitrophenol

Abstract: Co-crystallization of 4-nitrophenol (I) with five aminopyridines (4-aminopyridine 1, 3,4-diaminopyridine 2, 2,3-diaminopyridine 3, 3-aminopyridine 4, 2-amino-6-methylpyridine 5) and 2,4-diaminopyrimidine 6 resulted in six adducts with the ratio of components 2 : 1 in five and 1 : 1 in one final compounds. Single crystals were grown by slow evaporation technique using ethanol as a solvent. Five adducts with 1–5 crystallize in acentric P21 and Pna21 space groups, and one, 2(I)·6 – in centrosymmetric P21/c space group. Compounds 2(I)·1, 2(I)·2, 2(I)·3 are isomorphous, and demonstrate similar H-bonding patterns despite the differences in aminopyridine molecules. Compound 2(I)·5 is isomorphous to two previously reported compounds. Adducts 2(I)·1, 2(I)·2, 2(I)·3, 2(I)·5, 2(I)·6 represent organic salts composed of pyridinium/pyrimidinium cation, 4-nitrophenolate anion, and 4-nitrophenol neutral molecule. The H-bonded 4-nitrophenol–4-nitrophenolate anionic dimers were found in all compounds with 2 : 1 molar ratio. In adduct I·4 both molecules are in neutral form. The IR spectral data support crystallographic conclusions on salts formation. Plane wave pseudopotential density functional theory calculations were used to predict hyperpolarizability tensor components. Our calculations suggest 2(I)·3 as the best candidate for nonlinear optical materials (14 times more active than urea).

Single-Pixel Optical Fluctuation Analysis of Calcium Channel Function in Active Zones of Motor Nerve Terminals

Abstract: We used high-resolution fluorescence imaging and single-pixel optical fluctuation analysis to estimate the opening probability of individual voltage-gated calcium (Ca(2+)) channels during an action potential and the number of such Ca(2+) channels within active zones of frog neuromuscular junctions. Analysis revealed ∼36 Ca(2+) channels within each active zone, similar to the number of docked synaptic vesicles but far less than the total number of transmembrane particles reported based on freeze-fracture analysis (∼200-250). The probability that each channel opened during an action potential was only ∼0.2. These results suggest why each active zone averages only one quantal release event during every other action potential, despite a substantial number of docked vesicles. With sparse Ca(2+) channels and low opening probability, triggering of fusion for each vesicle is primarily controlled by Ca(2+) influx through individual Ca(2+) channels. In contrast, the entire synapse is highly reliable because it contains hundreds of active zones.

Treatment of Paraneoplastic Neurologic Disorders

Abstract: Paraneoplastic neurologic disorders are rare, autoimmune disorders, which can be broken down into two groups: those in which antibody response is directed against intracellular neuronal or neuroglial proteins (Group 1) and those in which the immune response is directed against antigens within or subjacent to the neuronal cell membrane (Group 2). In both groups, detection and treatment of the underlying neoplasm is critical and carries the best chance of clinical stabilization or remission.

Synaptic Pathophysiology and Treatment of Lambert-Eaton Myasthenic Syndrome.

Abstract: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca(2+) channels involved with neurotransmitter release. With less neurotransmitter release at the NMJ, LEMS patients experience debilitating muscle weakness. The underlying cause of LEMS in slightly more than half of all patients is small cell lung cancer, and cancer therapy is the priority for these patients. In the remaining cases, the cause of LEMS is unknown, and these patients often rely on symptomatic treatment options, as there is no cure. However, current symptomatic treatment options, such as 3,4-diaminopyridine (3,4-DAP), can have significant dose-limiting side effects; thus, additional treatment approaches would benefit LEMS patients. Recent studies introduced a novel Ca(2+) channel agonist (GV-58) as a potential therapeutic alternative for LEMS. Additionally, this work has shown that GV-58 and 3,4-DAP interact in a supra-additive manner to completely restore the magnitude of neurotransmitter release at the NMJs of a LEMS mouse model. In this review, we discuss synaptic mechanisms for reliability at the NMJ and how these mechanisms are disrupted in LEMS. We then discuss the current treatment options for LEMS patients, while also considering recent work demonstrating the therapeutic potential of GV-58 alone and in combination with 3,4-DAP.