1,2,3-Triazolylidene based complexes via post-modification of pincer click ligands

Preparation of 1,2,3-triazolylidene metal complexes by simple alkylation of triazolyl based parent species was demonstrated for the first time. Based on this post-modification approach, unprecedented tridentate Pd and Pt complexes bearing a 1,2,3-triazolylidene core were synthesized.     

Protamine neutralisation of low molecular weight heparins and their oligosaccharide components

Protamine sulphate is an effective inhibitor of heparin and is used clinically to neutralise both low molecular weight heparins (LMWH) and unfractionated heparin (UFH). However, protamine sulphate does not fully counter the anti-Xa effect of LMWH, even in excess (>40 μg to 1 IU/ml). To investigate the molecular basis for this observation, the residual potencies in the presence and absence of plasma as well as the molecular weight profiles of commercial LMWH neutralised with increasing amounts of protamine were measured. Materials over 5000 Da are preferentially neutralised by protamine. To further investigate this molecular weight dependence, monodisperse oligosaccharides were prepared from three commercial LMWHs. The specific anti-Xa activity for the fractions increased with molecular weight, and was found to vary between the three preparations for oligosaccharides of the same molecular weight. Our results indicate that protamine sulphate neutralisation is largely dependent on molecular weight, leading to the implication that LMWHs containing a larger proportion of small oligosaccharides will not be as effectively neutralised. Protamine sulphate neutralisation of any given LMWH is also affected by the specific anticoagulant activities of its low molecular weight components, which varies between LMWH products, presumably with the method of manufacture.     

Structurally powered synergic 2,2,6,6-tetramethylpiperidine bimetallics: new reflections through lithium-mediated ortho aluminations

Recent times have witnessed many notable advances in metalation chemistry with halide salt supported strategies and alkali-metal mediated metalation being particularly prominent. This article begins with a brief account of both of these avant garde metalation methods focusing on selected recent examples not covered previously in a review. New results in the area of Alkali-Metal Mediated Alumination (AMMAl) are also presented. Thus, the putative lithium aluminate base THF·Li(μ-TMP)(2)Al((i)Bu)(2) (4) is shown to act via TMP basicity to efficiently ortho deprotonate a variety of functionalized aromatic molecules at room temperature, tolerating carboxamide and halide functionalities. These metalated species are electrophilically quenched with elemental iodine. Crystal structure determinations of the metalated intermediates confirm unequivocally that direct alumination of the substrates has occurred. Since the homometallic lithium or aluminum reagents are unable to effect such deprotonations these reactions are synergic in nature and can be considered examples of AMMAl. Drawing together previously published work in the field of AMMAl, together with other pertinent experimental observations and new density functional theory (DFT) computational studies, we propose a potential rationale for the "unusual" reactivity patterns witnessed in this branch of heterometallic synthetic chemistry with respect to other Alkali Metal Mediated Metalations which appear to behave in a more conventional manner.     

Antibacterial Thiopeptide GE2270-Congeners from Nonomuraea jiangxiensis

Thiopeptides are macrocyclic natural products with potent bioactivity. Nine new natural thiopeptides (1–9) were obtained from a Nonomuraea jiangxiensis isolated from a terrestrial soil sample collected in Singapore. Even though some of these compounds were previously synthesized or isolated from engineered strains, herein we report the unprecedented isolation of these thiopeptides from a native Nonomuraea jiangxiensis. A comparison with the literature and a detailed analysis of the NMR and HRMS of compounds 1–9 was conducted to assign their chemical structures. The structures of all new compounds were highly related to the thiopeptide antibiotics GE2270, with variations in the substituents on the thiazole and amino acid moieties. Thiopeptides 1–9 exhibited a potent antimicrobial activity against the Gram-positive bacteria, Staphylococcus aureus with MIC₉₀ values ranging from 2 µM to 11 µM. In addition, all compounds were investigated for their cytotoxicity against the human cancer cell line A549, none of the compounds were cytotoxic.     

Synthesis, photophysical properties and in vitro photodynamic activity of axially substituted subphthalocyanines

A new series of subphthalocyanines substituted axially with an oligoethylene glycol chain [SPcB(OCH(2)CH(2))(n)OH, n = 3 (2) or 4 (3)] or a p-phenoxy oligoethylene glycol methyl ether chain [SPcBOC(6)H(4)(OCH(2)CH(2))(n)OCH(3), n = 2 (4) or 3 (5)] have been synthesised by substitution reactions of boron subphthalocyanine chloride SPcBCl (1) with the corresponding oligoethylene glycols, and characterised with various spectroscopic methods and elemental analysis. The molecular structure of one of these compounds (subphthalocyanine 4) has also been determined. As revealed by absorption spectroscopy, these compounds are essentially non-aggregated in DMF. The low aggregation tendency of these compounds results in a strong fluorescence emission and high efficiency to generate singlet oxygen. All these subphthalocyanines, being formulated with Cremophor EL, function as efficient photosensitisers and exhibit a high photocytotoxicity against HepG2 human hepatocarcinoma and HT29 human colon adenocarcinoma cells. The phenoxy analogues 4 and 5 show a relatively high photostability and are particularly potent towards these cell lines, with IC(50) values down to 0.02 microM.     

Spasmodic dysphonia and vocal fold paralysis:Outcomes of voice problems on work-related functioning

Patients at a university voice disorder clinic diagnosed with spasmodicdysphonia (SD, n = 68) or vocal fold paralysis (VFP, n = 57) reported vocal symptoms and adverse work outcomes in contrast to a nondisordered group (ND, n = 68). Patients with SD most frequently cited symptoms of effortfulness (57%) and weakness (54%), VFP cited hoarseness (70%) and weakness (60%), while the nondisordered reported hoarseness (28%). SD and VFP produced greater (p<.05) adverse work outcomes than the nondisordered in the past (SD: 65%, VFP: 41%, ND: 3%), potential future (SD: 78%, VFP: 65%, ND: 19%), and current job performance (SD: 64%, VFP: 46%, ND: 2%). These disorders significantly disrupt socioeconomic outcomes and research is needed to improve functional ability and quality of life.     

Functional impact of nodules: A case-comparison study

Patients diagnosed with nodules (NO = 40) in a large university hospital clinic and an age-stratum matched nondiseased group (ND = 200) described adverse outcomes of vocal impairment on work and work-related communications. NOs were significantly more likely than NDs to report symptoms of hoarseness (73% vs. 26%), high-note difficulty (70% vs. 20%), difficulty speaking with a lower voice (53% vs. 13%) and a tired voice (50% vs. 10%), and their greatest source of physical discomfort was associated with scratchiness (61% vs. 3%). The average number of symptoms was four in NOs and less than one in NDs. Nodule patients were most concerned about the effects their voice problem would have on their future career (78% vs. 24%) and 49% of NOS reported their voice problem had an adverse work effect in the past compared with 4% of NDs. Having a voice condition limited current job performance in 39% of the NO group but only in 2% of the ND group. The results suggest that a diagnosis of nodules plays a major role in disrupting careers and work activities and that available educational programs and additional research are needed for improving their functional ability and preventing adverse outcomes in the lives of individuals with voice disorders.