Synthesis of polydentate ligands and their self-assembly into helicates, meso-helicates and cyclic helicates

Described here is the synthesis and coordination chemistry of various ligands, L1 – L17. Some of the ligands presented form interesting supramolecular assemblies upon reaction with selected metal ions. Chapter 1 provides a general introduction to supramolecular chemistry and self-assembly. Chapter 2 introduces a new class of potentially hexadentate symmetrical ligands, L1 – L5. These ligands consist of two tridentate binding sites separated by a 1,3-phenylene spacer unit. Reaction of L1 with Zn(II) ions results in the formation of a pentanuclear circular helicate [Zn5(L1)5]10+, within the structure all five zinc ions are six-coordinate arising from coordination of two tridentate domains from two different ligand strands. This structure was shown to exist in both the solid state and in solution. Incorporation of various enantiopure units allowed variation of the terminal functional group of the ligand, L2 – L5. These ligands, upon coordination with Zn(II) ions, were shown to from supramolecular assemblies analogous to the pentanuclear species observed for L1. Additionally these ligands were shown to be diastereoselective, controlling the resulting supramolecular architecture giving up to 80% diastereomeric excess. Described in Chapter 3 are a number of potentially hexadentate N-donor ligands, L6 – L14. Each ligand possesses the same thiazole-pyridyl-pyridyl tridentate domains, with variation of the spacer unit. Upon coordination with selected transition metal ions these ligands resulted in the formation of dinuclear species. Reaction of L9 with Cd(II) results in the formation of a dinuclear double helicate, in which the two tridentate domains coordinate each metal ion and the ligands twist in the centre generating an ‘over and under’ arrangement. However, reaction of L9 with Co(II) results in the formation of a dinuclear meso-helicate, in which the ligands adopt a side-by-side configuration. This difference in structure is attributed to unfavourable steric interactions which prevent the formation of the Co(II) double helicate. Reaction of two of these ligands L10, which possesses an ethylene glycol chain, and L11, containing an amine group, with Cd(II) and camphorsulfonic acid results in the formation of a heteroleptic one-dimensional chain. Hydrogen bonding interactions between the protonated amine of L11 and the glycol chains of L10 results in a structure which contains both of these meso-helicate structures in an extended one-dimensional arrangement (([Cd2(L10)2][Cd2(L11-H)2])(ClO4)10)n. Chapter 4 reports the synthesis of three ligands, L15 – L17, each containing the same central phenol unit, and either a hydroxyl, pyridine or pyridine-N-oxide terminal unit. Reaction of each ligand with various trivalent lanthanide ions results in the formation of a dinuclear double helicate. In each structure the central phenol unit is deprotonated and bridges the two lanthanide ions giving [L2M2]4+. L17, which possesses the pyridine-N-oxide as the terminal group, effectively encompasses the cations minimising access for the coordination of any anions or solvent molecules. Photophysical measurements show that this ligand forms emissive complexes with a number of lanthanide ions, whilst the magnitude of the lifetime for [(L17)2Yb2]4+ (= 21.0 s) suggests that both Yb(III) ions are well-shielded from excited state quenching phenomena

Evaluation of a Hot Print System for the development of latent fingermarks on thermal paper:a pseudo-operational trial

Enhancement of latent fingermarks on thermal paper poses a number of problems when using traditional methods used for porous substrates due to blackening of the thermal layer as a result of polar solvents present within the reagents and high temperatures oxidising the acid/dye complex. Thus, methods which prevent such reactions are favoured for the development of latent prints on said substrates. A comparative pseudo-operational trial using UV, Hot Print System (HPS), ninhydrin and ThermaNIN was performed on 1000 thermal paper substrates gathered from various sources. The results indicated that the most effective method was an acetone pre-wash followed by ninhydrin. The sequence of HPS-ninhydrin was similarly effective when compared to ninhydrin as a sole technique. ThermaNIN produced fewer marks than ninhydrin but was superior to HPS. Whilst the HPS developed some fingermarks, there was only a very small number of marks uniquely developed by it.</p

Inhibition of the photochromic behaviour of a 3,3-diphenyl-3H-pyrano[3,2-f]quinoline ligand by coordination to Ag(I) ions

The synthesis and characterisation of a photoresponsive 3,3-diphenyl-3H-pyrano[3,2-f]quinoline ligand which contains both quinoline and thiazole N-donor moieties is described. This ligand acts as a bidentate N-donor ligand and the solid-state structure of a Ag(I) complex is reported. Whereas the free ligand exhibits typical photochromic behaviour, coordination with Ag(I) results in complete inhibition of the photochromic response. However, excitation wavelength dependent emission spectra demonstrated an increase in fluorescence response of the new Ag(I) complex

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Recommendations for effective documentation in regional anesthesia: an expert panel Delphi consensus project

Background and objectives: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. Methods: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. Results: Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. Conclusion: By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Palladium-catalysed direct alkenylation of sydnones

Sydnones have been directly functionalised with alkenyl halides and an alkynyl bromide under palladium catalysis

Steric control of the formation of dinuclear double helicate and dinuclear meso-helicate assemblies

We describe a ligand system that forms either a dinuclear double helicate or a dinuclear double mesocate dependent upon the size of the metal ion or the steric bulk of the ligand strand

Diastereoselective assembly of pentanuclear circular helicates

Reaction of a ligand which contains two N-donor and O-donor tridentate domains separated by a 1,3-phenylene spacer unit with Zn2+ ions results in a pentanuclear circular helicate [Zn5(L)5]10+ and this structure persists in both the solid and solution state. The formation of this high nuclearity species is governed by unfavourable steric interactions between the phenyl units which destabilize the simple linear helicate. Incorporation of enantiopure units within the ligand strand controls the diastereoselectivity with up to 80% d.e

Whole-genome analysis of giraffe supports four distinct species

Species is the fundamental taxonomic unit in biology and its delimitation has implications for conservation. In giraffe (Giraffa spp.), multiple taxonomic classifications have been proposed since the early 1900s.1 However, one species with nine subspecies has been generally accepted,2 likely due to limited in-depth assessments, subspecies hybridizing in captivity,3,4 and anecdotal reports of hybrids in the wild.5 Giraffe taxonomy received new attention after population genetic studies using traditional genetic markers suggested at least four species.6,7 This view has been met with controversy,8 setting the stage for debate.9,10 Genomics is significantly enhancing our understanding of biodiversity and speciation relative to traditional genetic approaches and thus has important implications for species delineation and conservation.11 We present a high-quality de novo genome assembly of the critically endangered Kordofan giraffe (G. camelopardalis antiquorum)12 and a comprehensive whole-genome analysis of 50 giraffe representing all traditionally recognized subspecies. Population structure and phylogenomic analyses support four separately evolving giraffe lineages, which diverged 230–370 ka ago. These lineages underwent distinct demographic histories and show different levels of heterozygosity and inbreeding. Our results strengthen previous findings of limited gene flow and admixture among putative giraffe species6,7,9 and establish a genomic foundation for recognizing four species and seven subspecies, the latter of which should be considered as evolutionary significant units. Achieving a consensus over the number of species and subspecies in giraffe is essential for adequately assessing their threat level and will improve conservation efforts for these iconic taxa