Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID).

Objective: The objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany.

Methods: The GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively.

Trans effect and trans influence: importance of metal mediated ligand-ligand repulsion.

The trans effect and trans influence were investigated and rationalized in the aminolysis, a typical nucleophilic substitution reaction, of trans-TPtCl2NH3 complexes (T = NH3, PH3, CO and C2H4) using energy decomposition analysis, both along the reaction paths and on the stationary points, and Natural Orbital for Chemical Valence analysis. In order to scrutinize the underlying principles and the origin of the kinetic trans effect, plausible structural constraints were introduced in the decomposition analysis, which allowed eliminating the distance dependence of the interaction energy components. It was established that the trans effect can be rationalized with the interaction of the TPtCl2 and NH3 fragments in the reactant state and TPtCl2 and (NH3)2 fragments in the transition state.

Cationic Ring-Opening Polymerization of 2-Propyl-2-oxazolines: Understanding Structural Effects on Polymerization Behavior Based on Molecular Modeling.

The surprising difference in the cationic ring-opening polymerization rate of 2-cyclopropyl-2-oxazoline versus 2--propyl-2-oxazoline and 2-isopropyl-2-oxazoline was investigated both experimentally and theoretically. The polymerization kinetics of all three oxazolines were experimentally measured in acetonitrile at 140 °C, and the polymerization rate constant () was found to decrease in the order -PropOx > -PropOx > -PropOx. Theoretical free energy calculations confirmed the trend for , and a set of DFT-based reactivity descriptors, electrostatics, and frontier molecular orbitals were studied to detect the factors controlling this peculiar behavior.

Reactivity of dicoordinated stannylones (Sn0) versus stannylenes (SnII): an investigation using DFT-based reactivity indices.

The reactivity of dicoordinated Sn(0) compounds, stannylones, is probed using density functional theory (DFT)-based reactivity indices and compared with the reactivity of dicoordinated Sn(II) compounds, stannylenes. For the former compounds, the influence of different types of electron-donating ligands, such as cyclic and acyclic carbenes, stannylenes and phosphines, on the reactivity of the central Sn atom is analyzed in detail. Sn(0) compounds are found to be relatively soft systems with a high nucleophilicity, and the plots of the Fukui function f(-) for an electrophilic attack consistently predict the highest reactivity on the Sn atom.

Electron-attachment-induced DNA damage: instantaneous strand breaks.

Low energy electron-attachment-induced damage in DNA, where dissociation channels may involve multiple bonds including complex bond rearrangements and significant nuclear motions, is analyzed here. Quantum mechanics/molecular mechanics (QM/MM) calculations reveal how rearrangements of electron density after vertical electron attachment modulate the position and dynamics of the atomic nuclei in DNA. The nuclear motions involve the elongation of the P-O (P-O(3') and P-O(5')) and C-C (C(3')-C(4') and C(4')-C(5')) bonds for which the acquired kinetic energy becomes high enough so that the neighboring C(3')-O(3') or C(5')-O(5') phosphodiester bond may break almost immediately.

Tuning aromaticity patterns and electronic properties of armchair graphene nanoribbons with chemical edge functionalisation.

Tuning the band gap of graphene nanoribbons by chemical edge functionalisation is a promising approach towards future electronic devices based on graphene. The band gap is closely related to the aromaticity distribution and therefore tailoring the aromaticity patterns is a rational way for controlling the band gap. In the present work, it is shown how the three distinct classes of aromaticity patterns already found for armchair graphene nanoribbons can be rationally tuned by chemical edge functionalisation to modify their electronic arrangement and band gap.

Relevance of grade 1 gray-scale ultrasound findings in wrists and small joints to the assessment of subclinical synovitis in rheumatoid arthritis.

Objective: To investigate the clinical relevance of grade 1 findings on gray-scale ultrasound (GSUS) of the joints in patients with rheumatoid arthritis (RA).

Methods: We examined the wrists and small joints of 100 patients with early or established RA and 30 healthy controls, using GSUS and power Doppler ultrasound (PDUS). Independent clinical assessment of all joints for tenderness and swelling according to the European League Against Rheumatism examination technique was performed.

Conformational control in [22]- and [24]pentaphyrins(1.1.1.1.1) by meso substituents and their N-fusion reaction.

meso-Substituted pentaphyrins(1.1.1.

Analysis of aromaticity in planar metal systems using the linear response kernel.

The linear response kernel is used to gain insight into the aromatic behavior of the less classical metal aromatic E4(2-) and CE4(2-) (E = Al, Ga) clusters. The effect of the systematic replacement of the aluminum atoms in Al4(2-) and CAl4(2-) by germanium atoms is studied using, Al3Ge-, Al2Ge2, AlGe3+, Ge4(2+), CAl3Ge-, CAl2Ge2, CAlGe3+, and CGe4(2+). The results are compared with the values of the delocalization index (δ(1,3)) and nucleus independent chemical shifts (NICS(zz)).

Platinum-mediated dinitrogen liberation from 2-picolyl azide through a putative Pt═N double bond containing intermediate.

2-Picolyl azide reacts with cis-[PtCl2(DMSO)2] to form the diimino complex [Pt(II)Cl2{NH═C(H)Py}] with subsequent dinitrogen liberation. The formation of the latter complex is scrutinized in a combined experimental and theoretical analysis. We establish in silico that the transformation involves a highly reactive intermediate containing a Pt═N double bond formed after the extrusion of N2 from the azide functionality.

Pushing the boundaries of intrinsically stable radicals: inverse design using the thiadiazinyl radical as a template.

In this study, for the first time inverse design was applied to search for the intrinsically most stable radical system in a predefined chemical space of enormous size by scanning in a rational way that entire chemical space. The focus was predominantly on thermodynamic stabilization effects, such as stabilization through resonance. Two different properties were optimized: a newly introduced descriptor called the radical delocalization value and the intrinsic stability via a previously established bond dissociation enthalpy model.

Electron capture by the thiyl radical and disulfide bond: ligand effects on the reduction potential.

The effect of non-polar and polar ligands and of monovalent cations on the one-electron reduction potential of the thiyl radical and the disulfide bond was evaluated. The reduction potentials E° for the CH3S(.)-nL/CH3S(-)-nL and CH3SSCH3-L/CH3SSCH3(.

Evaluating and Interpreting the Chemical Relevance of the Linear Response Kernel for Atoms.

Although a lot of work has been done on the chemical relevance of the atom-condensed linear response kernel χAB regarding inductive, mesomeric, and hyperconjugative effects as well as (anti)aromaticity of molecules, the same cannot be said about its not condensed form χ(r,r'). Using a single Slater determinant KS type ansatz involving second order perturbation theory, we set out to investigate the linear response kernel for a number of judiciously chosen closed (sub)shell atoms throughout the periodic table and its relevance, e.g.

σ, π aromaticity and anti-aromaticity as retrieved by the linear response kernel.

The chemical importance of the linear response kernel from conceptual Density Functional Theory (DFT) is investigated for some σ and π aromatic and anti-aromatic systems. The effect of the ring size is studied by looking at some well known aromatic and anti-aromatic molecules of different sizes, showing that the linear response is capable of correctly classifying and quantifying the aromaticity for five- to eight-membered aromatic and anti-aromatic molecules. The splitting of the linear response in σ and π contributions is introduced and its significance is illustrated using some σ-aromatic molecules.

Synthesis and structural characterization of heteroboroxines with MB2O3 core (M = Sb, Bi, Sn).

Reaction of organoantimony and organobismuth oxides (LSbO)(2) and (LBiO)(2) (where L is [2,6-bis(dimethylamino)methyl]phenyl) with four equivalents of the organoboronic acids gave new heteroboroxines LM[(OBR)(2)O] 1a-2c (for M = Sb: R = Ph (1a), 4-CF(3)C(6)H(4) (1b), ferrocenyl (1c); for M = Bi: R = Ph (2a), 4-CF(3)C(6)H(4) (2b), and ferrocenyl (2c)). Analogously, reaction between organotin carbonate L(Ph)Sn(CO(3)) and two equivalents of organoboronic acids yielded compounds L(Ph)Sn[(OBR)(2)O] (where R = Ph (3a), 4-CF(3)C(6)H(4) (3b), and ferrocenyl (3c)). All compounds were characterized by elemental analysis and NMR spectroscopy.

Topology switching in [32]heptaphyrins controlled by solvent, protonation, and meso substituents.

The switching of topology between "figure-eight", Möbius, and untwisted conformations in [32]heptaphyrins(1.1.1.

Effects of gender and age on serum concentrations of antidepressants under naturalistic conditions.

Therapeutic drug monitoring (TDM) data of antidepressant drugs are often evaluated using homogeneous samples of selected individuals without psychiatric or somatic comorbidity. These data may have limitations in transferability to everyday clinical practice. Hence, studies under naturalistic conditions are important to clarify the full clinical relevance of TDM of antidepressants.

How the conical intersection seam controls chemical selectivity in the photocycloaddition of ethylene and benzene.

The photocycloaddition reaction of benzene with ethylene has been studied at the CASSCF level, including the characterization of an extended conical intersection seam. We show that the chemical selectivity is, in part, controlled by this extended conical intersection seam and that the shape of the conical intersection seam can be understood in terms of simple VB arguments. Further, the shape and energetics of the asynchronous segment of the conical intersection seam suggest that 1,2 (ortho) and 1,3 (meta) will be the preferred chemical products with similar weight.

Effect of structural defects and chemical functionalisation on the intrinsic mechanical properties of graphene.

Due to its unique mechanical properties, graphene can be applied for reinforcement in nanocomposites. We analyse the Young's modulus of graphene at the semi-empirical PM6 level of theory. The internal forces are calculated and the Young's modulus is predicted for a finite graphene sheet when external strain is applied on the system.

Halogen bonding from a hard and soft acids and bases perspective: investigation by using density functional theory reactivity indices.

Halogen bonds between the trifluoromethyl halides CF(3)Cl, CF(3)Br and CF(3)I, and dimethyl ether, dimethyl sulfide, trimethylamine and trimethyl phosphine were investigated using Pearson's hard and soft acids and bases (HSAB) concept with conceptual DFT reactivity indices, the Ziegler-Rauk-type energy-decomposition analysis, the natural orbital for chemical valence (NOCV) framework and the non-covalent interaction (NCI) index. It is found that the relative importance of electrostatic and orbital (charge transfer) interactions varies as a function of both the donor and acceptor molecules. Hard and soft interactions were distinguished and characterised by atomic charges, electrophilicity and local softness indices.

Inverse design of molecules with optimal reactivity properties: acidity of 2-naphthol derivatives.

The design of molecules with optimal properties is an important challenge in chemistry because of the astronomically large number of possible stable structures that is accessible in chemical space. This obstacle can be overcome through inverse molecular design. In inverse design, one uses the computation of certain indices to design molecules with an optimal target property.

GABA concentration and GABAergic neuron populations in limbic areas are differentially altered by brain serotonin deficiency in Tph2 knockout mice.

While tryptophan hydroxylase-2 (Tph2) null mutant (Tph2(-/-)) mice are completely deficient in brain serotonin (5-HT) synthesis, the formation of serotonergic neurons and pathfinding of their projections are not impaired. However, 5-HT deficiency, during development and in the adult, might affect morphological and functional parameters of other neural systems. To assess the influence of 5-HT deficiency on γ-amino butyric acid (GABA) systems, we carried out measurements of GABA concentrations in limbic brain regions of adult male wildtype (wt), heterozygous (Tph2(+/-)) and Tph2(-/-) mice.

Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification.

Brain serotonin (5-HT) is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2).

Viability of Möbius topologies in [26]- and [28]hexaphyrins.

Recently, hexaphyrins have emerged as a promising class of π-conjugated molecules that display a range of interesting electronic, optical, and conformational properties, including the formation of stable Möbius aromatic systems. Besides the Möbius topology, hexaphyrins can adopt a variety of conformations with Hückel and twisted Hückel topologies, which can be interconverted under certain conditions. To determine the optimum conditions for viable Möbius topologies, the conformational preferences of [26]- and [28]hexaphyrins and the dynamic interconversion between the Möbius and Hückel topologies were investigated by density functional calculations.