Congenital Infection Influence on Early Brain Development Through the Gut-Brain Axis.

The mechanisms by which various pathogens cause congenital infections have been studied extensively, aiding in the understanding of the detrimental effects these infections can have on fetal/neonatal neurological development. Recent studies have focused on the gut-brain axis as pivotal in neurodevelopment, with congenital infections causing substantial disruptions. There remains controversy surrounding the purported sterility of the placenta as well as concerns regarding the effects of exposure to antibiotics used during pregnancy on neonatal microbiome development and how early exposure to microbes or antibiotics can shape the gut-brain axis. Long-term neurodevelopmental consequences, such as autism spectrum disorder, attention deficit hyperactivity disorder, and cerebral palsy, may be attributable, in part, to early life infection and changes in the immature gut microbiome. The goal of this review is thus to critically evaluate the current evidence related to early life infection affecting neurodevelopment through the gut-brain axis.

Type 1 Cytotoxic T Cells Increase in Placenta after Intrauterine Inflammation.

CD8+ T cells recognize non-self antigen by MHC class I molecules and kill the target cells by the release of proinflammatory cytokines such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). Our group previously reported an increase of CD8+ T-cell trafficking in the placenta with exposure to Lipopolysaccharides (LPS). CD8+ cytotoxic T cells have been classified into distinct subsets based upon cytokine production: Tc1 cells produce IFN-γ, Tc2 cells produce interleukin 4 (IL-4). Accordingly, the purpose of this research is to analyze the subsets of placenta CD8+ T cells. We hypothesized that LPS injection would induce a change of properties of CD8+ T cell and Tc1/Tc2 ratio. We investigated the subsets of CD8+ T cell infiltration to placenta and their specific function in response to LPS-induced inflammation in a mouse model. At embryonic (E) day 17, pregnant CD-1 dams received an intrauterine injection of 25 µg LPS in100 µl PBS or 100 µl of PBS only. Flow cytometry was used to quantify CD8+ T cells, evaluate the phenotype and subtypes, and detect markers of Tc1 and Tc2 cells in placenta, at 6 hours and 24 hours post injection (hpi). Intracellular staining and flow cytometry were performed to characterize cytokines produced by CD8+ T cells. Standard statistical analysis were employed. After 6 and 24 hours of LPS injection, total CD8 T cells increased (P<0.05). Tc1 cells expanded (P<0.05) in LPS-treated dams compared with the PBS group. The Tc1/Tc2 ratio was significantly higher in the LPS group than the PBS group (P<0.05). The expression of TNF-α and IFN-γ were increased in LPS group both at 6hpi and 24 hpi (P<0.05). We identified functional placental CD8+ T cell subtypes and found a significant increase ratio of Tc1/Tc2. Following IUI, CD8+ T cells induced inflammatory response in the placenta primarily via the production of Type 1 cytokines such as IFN-γ and TNF-α. We have provided evidence of a Tc1-bias response and cytokines in the mouse model of IUI.

Cu(I) complexes of bis(methyl)(thia/selena) salen ligands: Synthesis, characterization, redox behavior and DNA binding studies.

Mononuclear cuprous complexes 1 and 2, [{CH3E(o-C6H4)CH=NCH2}2Cu]ClO4; E=S/Se, have been synthesized by the reaction of bis(methyl)(thia/selena) salen ligands and [Cu(CH3CN)4]ClO4. Both the products were characterized by elemental analysis, ESI-MS, FT-IR, 1H/13C/77Se NMR, and cyclic voltammetry. The complexes possess tetrahedral geometry around metal center with the N2S2/N2Se2 coordination core. Cyclic voltammograms of complexes 1 and 2 displayed reversible anodic waves at E1/2=+0.08V and +0.10V, respectively, corresponding to the Cu(I)/Cu(II) redox couple. DNA binding studies of both the complexes were performed applying absorbance, fluorescence and molecular docking techniques. Competitive binding experiment of complexes with ct-DNA against ethidium bromide is performed to predict the mode of binding. The results indicate the groove binding mode of complexes 1 and 2 to DNA. The binding constants revealed the strong binding affinity of complexes towards ct-DNA.

Zn(II) and Cu(II) complexes of a new thiophene-based salphen-type ligand: solution-processable high-performance field-effect transistor materials.

A new thiophene-based salphen-type ligand, 1, and its Cu(II) and Zn(II) complexes, 1·Cu and 1·Zn·MeOH, were designed and synthesized. These metal organic complexes (MOCs), with ultra-close π-stacking interactions were explored as a novel class of active materials for organic field effect transistors (OFETs). The top-contact bottom gated OFETs fabricated from solution-processed thin films of 1·Cu and 1·Zn·MeOH exhibited excellent p-type mobilities (up to 0.7 and 1.5 cm(2) V(-1) s(-1), respectively).

Oxidative addition of disulfide/diselenide to group 10 metal(0) and in situ functionalization to form neutral thiasalen/selenasalen group 10 metal(II) complexes.

Three components, one pot synthesis of thiasalen/selenasalen Ni(II), Pd(II) and Pt(II) complexes, 14-19, by the oxidative addition of S-S/Se-Se bond of bis(o-formylphenyl)disulfide/-diselenide to Ni(0), Pd(0) and Pt(0) followed by in situ Schiff base formation with ethylenediamine is reported. S-S or Se-Se bonds were cleaved and coordinated to the metal center as thiolate (ArS(-)) or selenolate (ArSe(-)) while the formal oxidation state of metal centers was changed from '0' to '+2'. The disulfide/diselenide reacted with zero-valent metals at room temperature to give only the monometallic complexes. All complexes (except Pd-thiolate complex 15) were studied by single crystal X-ray crystallography and revealed the square planar geometry around metal centers.

Reaction time dependent formation of Pd(II) and Pt(II) complexes of bis(methyl)thiasalen podand.

Thiasalen podand 9 having S2N2 donor set has been synthesized by the condensation of 2-methylthiobenzaldehyde with ethylenediamine. The reaction of the thiasalen podand ligand with Pd(II) afforded two complexes depending on the reaction time. Shorter reaction time (5 min) afforded thioether complex 10; whereas with increase in reaction time (4 h) thioether-thiolate complex 11 was obtained via cleavage of one of the two S-C(Me) bonds of bis(methyl)thiasalen podand upon complexation. The reaction of 9 with Pt(II) afforded only thiolate-thioether complex 12 independent of the reaction time. The cleavage of both the S-C(Me) bonds of bis(methyl)thiasalen to afford bisthiolate complexes has never been observed. The structures of thiasalen podands and all three complexes have been determined by single crystal X-ray diffraction analysis. All three complexes possess a square planar geometry around the metal centres. Weak van der Waals interactions through C-H···F interactions are present in all three complexes leading to the formation of supramolecular synthons and the supramolecular structures are stabilized by aromatic π···π interactions, which leads to the formation of 3D pseudo-double helical network packing. Under similar conditions bis(methyl)salen did not form any complexes with Pd(II) and Pt(II).

Synthesis, characterization and coordination properties of bis(alkyl)selenosalen ligands.

New bis (alkyl) selenosalen podand ligands having Se2N2 donor sites have been synthesized by the condensation of unsymmetrical o-formylphenyl alkyl selenide (1-3) with ethylenediamine. The reaction of bis(alkyl)selenosalen podands with Pd(II) and Pt(II) afforded selenoether-selenolate coordination complexes 7-10via cleavage of one of the two Se-C(alkyl) bonds of bis(alkyl)selenosalen podands upon complexation. DFT calculations revealed that the cleavage of Se-C(alkyl) bonds occurred possibly via S(N)2 mechanism instead of a sequence of oxidative addition and reductive elimination reactions. The spectral data and elemental analyses confirmed the formation of selenoether-selenolate complexes. The structures of the podands N,N'-bis[(2-methylseleno)phenylmethylene]-1,2-ethanediamine (4), N,N'-bis[(2-decylseleno)phenylmethylene]-1,2-ethanediamine (5) and the selenoether-selenolate complex 8 have been determined by single crystal X-ray diffraction analysis. The crystal structure of 5 showed SeH interaction with a ladder like 3D supramolecular arrangement via interdigitation of long alkyl chains. Comparison of crystal packing of podands 4 and 5 indicates that the alkyl chain length has significant impact on the crystal packing. The platinum selenolate complex 8 shows a square planar arrangement around the Pt centre, where the Se atoms in the selenolate and the selenoether have nearly equal Pt-Se bond length.

Twisting (conformational changes)-based selective 2D chalcogeno podand fluorescent probes for Cr(III) and Fe(II).

The fluorenoazomethine containing chalcogeno podand fluorescent probes having N, O/S/Se coordinating donor unit show donor specific 'turn-on' recognition property towards metals (Cr(III), Fe(II) and Cu(II)), where the fluorescence signals are controlled by the conformational change of the ligand framework on binding with the metal ion.

3,4-Ethylenedioxythiophene and 3,4-ethylenedioxyselenophene: synthesis and reactivity of C(alpha)-Si bond.

A synthetic approach to synthesize EDOT and EDOS from a common precursor 5 is reported. The method involves zirconocene dichloride mediated reaction of a common diyne 5 followed by treatment with disulfur dichloride (S(2)Cl(2)) and in situ prepared selenium dichloride (SeCl(2)). The higher lability of alpha-trimethylsilyl group in EDOS compared to EDOT is explained using DFT calculations.

Intramolecular interactions between chalcogen atoms: organoseleniums derived from 1-bromo-4-tert-butyl-2,6-di(formyl)benzene.

[structure: see text] The synthesis and characterization of a series of low-valent organoselenium compounds derived from 1-bromo-4-tert-butyl-2,6-di(formyl)benzene (22) is described. The synthesis of diselenide 25 was achieved by the lithiation route whereas bis(4-tert-butyl-2,6-di(formyl)phenyl) diselenide (26) was synthesized by treating 22 with disodium diselenide. A series of monoselenides (27, 28, and 29) was obtained by facile nucleophilic substitution of bromine in 22, using the corresponding selenolates as nucleophiles. The halogenation reactions of bis(4-tert-butyl-2,6-di(formyl)phenyl) diselenide (26) did not afford the corresponding selenenyl halides but resulted in the isolation of an unexpected cyclic selenenate ester 34 as a product. The selenide 32 was synthesized by the treatment of dimethoxymethyl diselenide with trilithiated 2-bromo-5-tert-butyl-N,N'-di(phenyl)isophthalamide. The existence of potential Se...O intramolecular nonbonding interactions was examined by IR, (1)H, and (77)Se NMR spectroscopy, X-ray crystallography, and computational studies. The X-ray crystal structures of 26 and 27, having two ortho formyl groups, reveal the absence of any Se...O interactions. However, the Se...O interactions were observed in the selenenate ester 34 where one of the formyl groups has been utilized for the selenenate ring formation. The crystal structures of 26 and 27 exhibited intermolecular short-range C-H...Se interactions (hydrogen bonding). Although there are four heteroatoms in carbamoyl moieties ortho to selenium capable of forming a five-membered ring on intramolecular coordination, no such intramolecular Se...X (X = N, O) interaction was observed in the crystal structure of 32. The density functional theory calculations at the B3LYP/6-31G* level predicted that for all the diformyl systems (47a-c, 48a-c), the anti,anti conformer (when both formyl oxygen atoms point away from the selenium) is more stable. This preference was found to be reversed in the monoformyl-substituted systems (50a,b, 51a,b), where the syn conformer (when formyl oxygen is near the selenium) is energetically more favorable than the anti conformer.

Synthesis and structure of mercurous ion and dinuclear lead(II) complexes of the 28-membered selenaaza macrocycle: dominance of the chelate ring size effect and conformational requirement over soft-soft interactions.

The flexible and larger ring size macrocycle 4 (C(36)H(46)N(6)Se(2)) afforded stable complex 5 [Hg(2)(PF(6))(2)[C(36)H(46)N(6)Se(2)]] on treatment with 1 equiv of mercuric acetate followed by addition of NH(4)PF(6). The reaction of Pb(OCOCH(3))(2).4H(2)O with 4 followed by treatment with NH(4)PF(6) resulted in a dinuclear lead complex (6) [Pb(2)(PF(6))(2)(OCOCH(3))(2)[C(36)H(46)N(6)Se(2)]]. The crystal structures of complexes 5 and 6 are described: C(36)H(46)F(12)Hg(2)N(6)P(2)Se(2) a = 9.5106(5) A, b = 11.5222(6) A, c = 11.8161(6) A, alpha = 115.6110(10) degrees , beta = 96.5190(10) degrees , gamma = 106.2910(10) degrees , monoclinic, P, Z =1; C(44)H(57)F(12)N(8)O(4)P(2)Pb(2)Se(2) a = 9.4668(5) A, b = 11.9937(6) A, c = 25.2319(14) A, alpha = 102.4130(10) degrees , beta = 97.6130(10) degrees , gamma = 94.8540(10) degrees , monoclinic, P, Z = 2. The crystal structure of 5 revealed that Hg(2)(2+) is trapped inside the cavity of the macrocycle. The geometry around the mercurous ion is antiprismatic with Hg(2)(2+) coordinating to six nitrogen atoms forming four five-membered rings, and there is no interaction between the mercurous ion and the selenium donor atoms. The single crystal X-ray crystal structure of 6 indicates a distorted octahedral geometry around each lead atom in the cavity of the macrocycle due to presence of the sterochemically active lone pair on Pb(II). The octahedral geometry around each Pb(II) is satisfied by coordination to 3 nitrogen atoms, two oxygen atoms of the chelating acetate group, and bridging of one of the oxygen atoms of the nearby acetate.