Insights into the strength and nature of carbene···halogen bond interactions: a theoretical perspective

Halogen-bonding, a noncovalent interaction between a halogen atom X in one molecule and a negative site in another, plays critical roles in fields as diverse as molecular biology, drug design and material engineering. In this work, we have examined the strength and origin of halogen bonds between carbene CH₂ and XCCY molecules, where X?=?Cl, Br, I, and Y?=?H, F, COF, COOH, CF₃, NO₂, CN, NH₂, CH₃, OH. These calculations have been carried out using M06-2X, MP2 and CCSD(T) methods, through analyses of surface electrostatic potentials V _S(r) and intermolecular interaction energies. Not surprisingly, the strength of the halogen bonds in the CH₂···XCCY complexes depend on the polarizability of the halogen X and the electron-withdrawing power of the Y group. It is revealed that for a given carbene···X interaction, the electrostatic term is slightly larger (i.e., more negative) than the dispersion term. Comparing the data for the chlorine, bromine and iodine substituted CH₂···XCCY systems, it can be seen that both the polarization and dispersion components of the interaction energy increase with increasing halogen size. One can see that increasing the size and positive nature of a halogen’s σ-hole markedly enhances the electrostatic contribution of the halogen-bonding interaction.

Theoretical study on cooperative effects between X⋯N and X⋯Carbene halogen bonds (X = F,Cl,Br and I)

Quantum chemical calculations are performed to study the interplay between halogen?nitrogen and halogen?carbene interactions in NCX?NCX?CH₂ complexes, where X?=?F, Cl, Br and I. Molecular geometries and interaction energies of dyads and triads are investigated at the MP2/aug-cc-pVTZ level of theory. It is found that the X?N and X?C_carbene interaction energies in the triads are larger than those in the dyads, indicating that both the halogen bonding interactions are enhanced. The estimated values of cooperative energy E _coop are all negative with much larger E _coop in absolute value for the systems including iodine. The nature of halogen bond interactions of the complexes is analyzed using parameters derived from the quantum theory atoms in molecules methodology and energy decomposition analysis.

Innate immune responses of a scleractinian coral to vibriosis

Scleractinian corals are the most basal eumetazoan taxon and provide the biological and physical framework for coral reefs, which are among the most diverse of all ecosystems. Over the past three decades and coincident with climate change, these phototrophic symbiotic organisms have been subject to increasingly frequent and severe diseases, which are now geographically widespread and a major threat to these ecosystems. Although coral immunity has been the subject of increasing study, the available information remains fragmentary, especially with respect to coral antimicrobial responses. In this study, we characterized damicornin from Pocillopora damicornis, the first scleractinian antimicrobial peptide (AMP) to be reported. We found that its precursor has a segmented organization comprising a signal peptide, an acidic proregion, and the C-terminal AMP. The 40-residue AMP is cationic, C-terminally amidated, and characterized by the presence of six cysteine molecules joined by three intramolecular disulfide bridges. Its cysteine array is common to another AMP and toxins from cnidarians; this suggests a common ancestor, as has been proposed for AMPs and toxins from arthropods. Damicornin was active in vitro against Gram-positive bacteria and the fungus Fusarium oxysporum. Damicornin expression was studied using a combination of immunohistochemistry, reverse phase HPLC, and quantitative RT-PCR. Our data show that damicornin is constitutively transcribed in ectodermal granular cells, where it is stored, and further released in response to nonpathogenic immune challenge. Damicornin gene expression was repressed by the coral pathogen Vibrio coralliilyticus. This is the first evidence of AMP gene repression in a host-Vibrio interaction.     

The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties

Mesenchymal stromal cells (MSC) can be expanded from different sources. We compared the influence of inflammation and TLR ligation on the phenotype and function of MSC derived from bone marrow (BM), adipose tissue (AT), and Wharton’s jelly (WJ). WJ-MSC were featured by a lack of TLR4 expression. While inflammation upregulated TLR3 in all three MSC types, TLR4 upregulation was observed only on BM-MSC. TLR ligation increased the production of inflammatory cytokines in BM- and AT-MSC but not in WJ-MSC and augmented anti-inflammatory cytokines in AT-MSC. Although inflammation increased in all MSC types the secretion of inflammatory cytokines, additional TLR triggering did not have further effect on WJ-MSC. The immunosuppressive potential of WJ-MSC on MLR was affected neither by inflammation nor by TLR triggering. This resistance was related to an overproduction of HGF. These data indicate that MSC source could be of importance while designing immunomodulating cell therapy in transplantation.     

A click procedure with heterogeneous copper to tether technetium-99m chelating agents and rhenium complexes. Evaluation of the chelating properties and biodistribution of the new radiolabelled glucose conjugates

An efficient protocol was developed to tether chelating agents and rhenium complexes onto a glucoside scaffold with a heterogeneous copper catalyst via click chemistry. The supported catalyst avoids the formation of unwanted copper complexes during the cyclisation step. The possibility to graft a pre-chelated M(CO)₃ core by click chemistry onto a biomolecule was highlighted for the first time. ^99mTc(CO)₃-glucoconjugates displayed excellent in vitro stability, a fast in vivo blood clearance and a low specific organ uptake or long-term retention in spleen and stomach.     

Electrochemical detection of the MT-ND6 gene and its enzymatic digestion: Application in human genomic sample

A simple electrochemical biosensor was developed for the detection of the mitochondrial NADH dehydrogenase 6 gene (MT-ND6) and its enzymatic digestion by BamHI enzyme. This biosensor was fabricated by modification of a glassy carbon electrode with gold nanoparticles (AuNPs/GCE) and a probe oligonucleotide (ssDNA/AuNPs/GCE). The probe, which is a thiolated segment of the MT-ND6 gene, was deposited by self-assembling immobilization on AuNPs/GCE. Two indicators including methylene blue (MB) and neutral red (NR) were used as the electroactive indicators and the electrochemical response of the modified electrode was measured by differential pulse voltammetry. The proposed biosensor can detect the complementary sequences of the MT-ND6 gene. Also the modified electrode was used for the detection of an enzymatic digestion process by BamHI enzyme. The electrochemical biosensor can detect the MT-ND6 gene and its enzymatic digestion in polymerase chain reaction (PCR)-amplified DNA extracted from human blood. Also the biosensor was used directly for detection of the MT-ND6 gene in all of the human genome.     

Protective effects of Ephedra pachyclada extract on mouse models of carbon tetrachloride- induced chronic and acute liver failure

Inflammation and oxidation are two important factors in the pathogenesis of liver. Ephedra pachyclada (EP) is a traditional medical herb that has anti-inflammatory and anti-oxidant activities. During this study, anti-oxidant activities of the EP extract was measured in vitro by 2,2′- diphenyl-1-picrylhydrazyl (DPPH) and β-Carotene bleaching assays. Then, we examined possible in vivo hepatoprotective effects of EP extract on mouse models of carbon tetrachloride (CCl₄)-induced chronic and acute liver failure. To produce mouse models of chronic and acute liver injuries, male SW1 mice were interaperitoneally injected with 1 ml/kg body weight (bw) CCl₄ biweekly for 42 days and a single dose of 2 ml/kg bw, respectively. In the experimental groups, mouse models were treated with low (140 mg/kg bw) and high (1400 mg/kg bw) doses of the EP extract. Olive oil and water treated mice were considered as controls during model derivation and EP extract treatment respectively. The results showed the antioxidant activity of EP extract and a significant reduction of all parameters of CCl₄-induced liver injury such as relative liver weight, necrosis, fibrosis, inflammation, and serum aspartate transaminase (AST) and alanine aminotransferase (ALT) in mouse models of acute and chronic liver injury treated with EP extract. Therefore, EP induces its hepatoprotective effects probably by suppressing oxidative stress and inhibit inflammation in the liver and is able to protect the liver against CCl₄-induced acute and chronic injuries.     

HLA-DRBl and susceptibility to kidney allograft rejection in Southern Iranian patients

Kidney transplantation is the best treatment option for the patients with end-stage renal disease. Viral infections and genetic factors such as HLA-II antigens may affect the kidney transplant outcome. The compatibility of HLA-DRB1 molecules in the survival of kidney transplant is important. Also, the correlation between these molecules and viral infections is significant. The current study investigates the allele frequency of HLA-DRB1 in 41 recipient kidney transplant and 203 normal healthy controls by polymerase chain reaction using sequence specific primers. Moreover the relation between HLA-DRB1 allelic groups and hepatitis B, hepatitis C and cytomegalovirus viral infections was also studied. However statistical analysis of the allele frequencies didn’t show any significant association between HLA-DRB1 allelic group distributions or sharing and susceptibility to acute kidney transplant rejection (P > 0.05). Comparing the allele frequencies between HLA-DRB1*14 and DRB1*04 allelic showed a significant difference in controls and patients (P = 0.03 and P = 0.05 respectively). The results of the present study also showed a significant association between possession of HLA-DRB1*07 allele in kidney transplant recipients and hepatitis C virus infection (P = 0.009). In conclusion however the results of the present study did not showed relation between HLA-DRB1 allele’s frequencies or sharing and kidney transplantation outcome, the results indicated that HLA-DRB1 alleles may susceptible individuals to renal disease or play a role in susceptibility to viral infection in kidney transplant patients.