Indium(III)-Catalyzed Haloalkynylation Reaction of Alkynes.

Green chemistry strives for sustainability at the molecular level and is gaining increasing relevance in the development of chemical reactions. The haloalkynylation reaction is a highly atom-economical C-C coupling reaction that was previously only achieved using transition metal catalysts. It enables the introduction of an alkyne unit and a halogen atom into the target molecule. Herein, we present a haloalkynylation reaction catalyzed by indium(III) halides. The use of indium(III) bromide as a catalyst leads exclusively to the cis addition products with yields up to 86 %. In addition, iodoacetylenes can be applied for the first time for the haloalkynylation reaction of internal alkynes which is an important step forward in the development of industrially relevant and sustainable catalysts. In contrast to gold catalysis, which proceeds via a similar mechanism, the use of alkyl-substituted haloacetylenes as reagents is also possible. Based on 13C labeling experiments and quantum chemical calculations, we postulate two possible mechanisms for the indium(III)-catalyzed haloalkynylation reactions.

Evaluation of factors associated with surgical site infection in equine proximal interphalangeal joint arthrodesis: 54 cases (2010-2019).

BACKGROUND: The frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered. OBJECTIVES: To determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols. METHODS: Records were evaluated (2010-2019), and horses undergoing PIPJ arthrodesis were identified. Patient signalment, supervising surgeon, reason for surgery, limb, implants placed, anaesthetic time, duration casting/coaptation postoperatively, antibiotic regimen and incidence/onset SSI were recorded. Bayesian and frequentist logistic regressions were used to estimate the contribution of covariates to infection occurrence. RESULTS: Fifty-four PIPJ arthrodeses were performed. SSI occurred in 2/54 (3.7%) on day 15,30. Arthrodesis was performed most commonly for osteoarthritis (33/54, 61.1%), fracture (11/54, 20.4%), and subluxation (5/54, 9.3%). Perioperative systemic antibiotics were administered 1-3 days (15/54, 27.8%) or > 3 days (39/54, 72.2%). Antibiotic protocols included cefazolin/gentamicin (20/54, 37%), cefazolin/gentamicin/doxycycline (14/54, 25.9%) and potassium penicillin/gentamicin (10/54, 18.5%). Regional limb perfusion was performed preoperatively 31/54 (57.4%) and postoperatively 7/54 (13%). Survival to dismissal was 98.1% (53/54 horses) with one horse euthanized due to support limb laminitis. No association was identified between antibiotic selection or duration (1-3 vs. > 3 days), pre-operative regional antibiotic perfusion, intraoperative antibiotic lavage or anaesthetic time (< or > 3 h) and SSI; however, modelling was complicated by quasi-complete or complete separation of the data. Bayesian analysis (but not frequentist analysis) indicated an association between post-operative regional antibiotic perfusion and SSI. Limitations include the retrospective nature of data collection and the low rate of infection overall. CONCLUSIONS: The prevalence of SSI in this population was lower than that in previous reports of equine orthopaedic internal fixation. There was no difference in SSI rate in cases administered systemic antibiotics for 1-3 days or >3 days, or for those horses that did or did not receive preoperative regional antibiotic perfusion.

1,3-Chlorine Shift to a Vinyl Cation: A Combined Experimental and Theoretical Investigation of the E-Selective Gold(I)-Catalyzed Dimerization of Chloroacetylenes.

Metal-catalyzed dimerization reactions of terminal acetylenes are well known in the literature. However, only a few examples of the dimerization of halogen-substituted acetylenes are described. The products of the latter metal-catalyzed dimerization are the branched head-to-tail enynes. The formation of the corresponding linear head-to-head enynes has not been reported yet. Herein, we demonstrate by means of quantum chemical methods and experiments that the head-to-head dimerization of chloroarylacetylenes can be achieved via mono gold catalysis. Under the optimized conditions, a clean and complete conversion of the starting materials is observed and the dimeric products are obtained up to 75% NMR yield. A mechanistic investigation of the dimerization reaction reveals that the branched head-to-tail vinyl cation is energetically more stable than the corresponding linear head-to-head cation. However, the latter can rearrange by an unusual 1,3-chlorine shift, resulting in the highly stereoselective formation of the trans product, which corresponds to the gold complex of the head-to-head E-enyne. The activation barrier for this rearrangement is extremely low (ca. 2 kcal/mol). As the mono gold-catalyzed dimerization can be conducted in a preparative scale, this simple synthesis of trans-1,2-dichloroenynes makes the gold(I)-catalyzed head-to-head dimerization of chloroarylacetylenes an attractive method en route to more complex conjugated enyne systems and their congeners.

Male fertility status is associated with DNA methylation signatures in sperm and transcriptomic profiles of bovine preimplantation embryos.

BACKGROUND: Infertility in dairy cattle is a concern where reduced fertilization rates and high embryonic loss are contributing factors. Studies of the paternal contribution to reproductive performance are limited. However, recent discoveries have shown that, in addition to DNA, sperm delivers transcription factors and epigenetic components that are required for fertilization and proper embryonic development. Hence, characterization of the paternal contribution at the time of fertilization is warranted. We hypothesized that sire fertility is associated with differences in DNA methylation patterns in sperm and that the embryonic transcriptomic profiles are influenced by the fertility status of the bull. Embryos were generated in vitro by fertilization with either a high or low fertility Holstein bull. Blastocysts derived from each high and low fertility bulls were evaluated for morphology, development, and transcriptomic analysis using RNA-Sequencing. Additionally, DNA methylation signatures of sperm from high and low fertility sires were characterized by performing whole-genome DNA methylation binding domain sequencing. RESULTS: Embryo morphology and developmental capacity did not differ between embryos generated from either a high or low fertility bull. However, RNA-Sequencing revealed 98 genes to be differentially expressed at a false discovery rate < 1%. A total of 65 genes were upregulated in high fertility bull derived embryos, and 33 genes were upregulated in low fertility derived embryos. Expression of the genes CYCS, EEA1, SLC16A7, MEPCE, and TFB2M was validated in three new pairs of biological replicates of embryos. The role of the differentially expressed gene TFB2M in embryonic development was further assessed through expression knockdown at the zygotic stage, which resulted in decreased development to the blastocyst stage. Assessment of the epigenetic signature of spermatozoa between high and low fertility bulls revealed 76 differentially methylated regions. CONCLUSIONS: Despite similar morphology and development to the blastocyst stage, preimplantation embryos derived from high and low fertility bulls displayed significant transcriptomic differences. The relationship between the paternal contribution and the embryonic transcriptome is unclear, although differences in methylated regions were identified which could influence the reprogramming of the early embryo. Further characterization of paternal factors delivered to the oocyte could lead to the identification of biomarkers for better selection of sires to improve reproductive efficiency.