Highly efficient, stoichiometric radical exchange reactions using isoindoline profluorescent nitroxides

Exchange reactions between the isoindoline profluorescent nitroxide 1,1,3,3-tetramethyldibenzo[e,g]isoindolin-2-yloxyl (TMDBIO) and a TEMPO capped polystyrene were carried out. High conversions to the desired products were achieved using only stoichiometric ratios of nitroxide relative to polymer. The scope of this study was expanded by exploiting a di-nitroxide 9,10-bis(5-[1,1,3,3-tetramethylisoindolin-2-yloxy])anthracene (BTMIOA) as a connector between two polymer chains forming PS–nitroxide–PS systems.

Critical communications research in Australia : from radical populism to creative industries

This paper tracks the development of critical communicatiosn research in Australia over a 30 year period. It assesses the relative significance of critical theory, Marxist political economy and cultural studies to the development of such a tradition. it also evaluates the rise of 'creative industries' dicourse as an emergent development in the field, and a distinctive contribution of Australian media and communications research.

The synthesis of novel nitroxides and their application as small-molecule antioxidants and profluorescent probes for oxidative stress

The detection and potential treatment of oxidative stress in biological systems has been explored using isoindoline-based nitroxide radicals. A novel tetraethyl-fluorescein nitroxide was synthesised for its use as a profluorescent probe for redox processes in biological systems. This tetraethyl system, as well as a tetramethyl-fluorescein nitroxide, were shown to be sensitive and selective probes for superoxide in vitro. The redox environment of cellular systems was also explored using the tetramethylfluorescein species based on its reduction to the hydroxylamine. Flow cytometry was employed to assess the extent of nitroxide reduction, reflecting the overall cellular redox environment. Treatment of normal fibroblasts with rotenone and 2-deoxyglucose resulted in an oxidising cellular environment as shown by the lack of reduction of the fluorescein-nitroxide system. Assessment of the tetraethyl-fluorescein nitroxide system in the same way demonstrated its enhanced resistance to reduction and offers the potential to detect and image biologically relevant reactive oxygen species directly. Importantly, these profluorescent nitroxide compounds were shown to be more effective than the more widely used and commercially available probes for reactive oxygen species such as 2’,7’-dichlorodihydrofluorescein diacetate. Fluorescence imaging of the tetramethyl-fluorescein nitroxide and a number of other rhodamine-nitroxide derivatives was undertaken, revealing the differential cellular localisation of these systems and thus their potential for the detection of redox changes in specific cellular compartments. As well as developing novel methods for the detection of oxidative stress, a number of novel isoindoline nitroxides were synthesised for their potential application as small-molecule antioxidants. These compounds incorporated known pharmacophores into the isoindoline-nitroxide structure in an attempt to increase their efficacy in biological systems. A primary and a secondary amine nitroxide were synthesised which incorporated the phenethylamine backbone of the sympathomimetic amine class of drugs. Initial assessment of the novel primary amine derivative indicated a protective effect comparable to that of 5-carboxy-1,1,3,3- tetramethylisoindolin-2-yloxyl. Methoxy-substituted nitroxides were also synthesised as potential antioxidants for their structural similarity to some amphetamine type stimulants. A copper-catalysed methodology provided access to both the mono- and di-substituted methoxy-nitroxides. Deprotection of the ethers in these compounds using boron tribromide successfully produced a phenolnitroxide, however the catechol moiety in the disubstituted derivative appeared to undergo reaction with the nitroxide to produce quinone-like degradation products. A novel fluoran-nitroxide was also synthesised from the methoxy-substituted nitroxide, providing a pH-sensitive spin probe. An amino-acid precursor containing a nitroxide moiety was also synthesised for its application as a dual-action antioxidant. N-Acetyl protection of the nitroxide radical was necessary prior to the Erlenmeyer reaction with N-acetyl glycine. Hydrolysis and reduction of the azlactone intermediate produced a novel amino acid precursor with significant potential as an effective antioxidant.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Profluorescent nitroxides as sensitive probes of oxidative change and free radical reactions

This paper presents a review on the use of tethered nitroxide–fluorophore molecules as probes of oxidative change and free radical generation and reaction. The proximity of the nitroxide free radical to the fluorophore suppresses the normal fluorescence emission process. Nitroxide free radical scavenging, metabolism or redox chemistry return the system to its natural fluorescent state and so these tethered nitroxide–fluorophore molecules are described as being profluorescent. A survey of profluorescent nitroxides found in the literature is provided as well as background on the mechanism of action and applications of these compounds as fluorometric probes within the fields of biological, materials and environmental sciences.

Living characteristics of the free-radical ring-closing polymerization of diallyldimethylammonium chloride

In this communication we provide the most recent results on RAFT-mediated ring-closing polymerization of diallyldimethylammonium chloride (DADMAC). The polymerization was carried out in aqueous solution employing 2,2′-azobis(2-methylpropionamidine)-dihydrochloride as the free radical initiator and trithiocarbonate RAFT agent (2-{[(dodecylsulfanyl)carbonothioyl sulfanyl]}propanoic acid, DoPAT) as the controlling RAFT agent. The results show that – while the system is not as completely controlled as previously described – it is nevertheless possible to mediate the polymerization of DADMAC and impart some living characteristics onto the system. The initial study on the RAFT-mediated polymerization of DADMAC may have overestimated the degree of livingness within this reaction. However, it is possible – at low conversions – for some living characteristics to be observed, as the evolution of molecular weight with conversion is linear. In addition, polymers with a reasonably narrow polydispersity can be isolated.

Is globalisation an enabler of radical innovation in Toyota?

Prior evidence from the fields of innovation management and supplier relations predicts that Japanese firms should be naturally disadvantaged in developing and deploying radical innovations. But this conclusion is inconsistent with recent developments in the automotive industry. This paper presents secondary case study data focusing on fuel cell powered vehicles and hybrid cars to show that Toyota, one of Japan's largest and most influential corporations, is capable of developing radically new technologies, and is in several respects better at this sort of innovation than the rest of the global automotive industry.

What the hare can teach the tortoise about make-buy strategies for radical innovations

Purpose of this paper – The purpose of this investigation is to help establish: whether or not strong relationships between suppliers and customers improve performance; and if prescriptive frameworks on outsourcing radical innovations are dependent on industry clockspeed. Design/methodology/approach – A survey of UK-based manufacturers, followed by a statistical analysis. Findings – Long-term supplier links seem not to play a role in the development of radical innovations. Moreover, industry clockspeed has no significant bearing on the success or failure of any outsourcing strategy for radically new technologies. Research limitations/implications – Literature about outsourcing in the face of radical innovation can be more confidently applied to industries of all clockspeeds. Practical implications – Prescriptions for fast clockspeed industries should be applied more broadly: all industries should maintain a high degree of vertical integration in the early days of a radical innovation. Originality/value – Prior papers had explored whether or not a company should outsource radical innovations, but none had determined if this is equally true for slow industries and fast ones. Therein lies the original contribution of this paper.

Outsourcing strategies for radical innovations: does industry clockspeed make a difference?

Purpose – To determine whether or not clockspeed is an important variable in outsourcing strategies throughout the development of radical innovations. Design/methodology/approach – An internet-based survey of manufacturing firms from all over the world. Findings – An industry's clockspeed does not play a significant role in the success or failure of a particular outsourcing strategy for a radical innovation. Research limitations/implications – Conclusions from earlier research in this area are not necessarily industry-specific. Practical implications – Lessons learned via previous investigations about the computer industry need not be confined to that sector. Vertical integration may be a more robust outsourcing strategy when developing a radical innovation in industries of all clockspeeds. Originality/value – Previous research efforts in this field focused on a single technology jump, but this approach may have overlooked a potentially important variable: industry clockspeed. Thus, this investigation explores whether clockspeed is an important factor.

Designing radical business model innovation : a case study

“The process of innovation is often seen as being very linear, with research results, new technologies or user insights being channelled, often prematurely, into specific products and process” (Kyffin and Gardien 2009). It is precisely this perception of innovation-as-linear-process which this paper seeks to challenge. While there are many current theories and much contemporary literature available which discuss the management and catalysts of innovation, what is missing are examples of how innovation occurs from the application of these theories and literature (Wrigley & Bucolo 2010). This paper addresses both this gap and perceptions of the viability of linear innovation by presenting a case study for the commercialisation of a core technology (a cleantech, semi-portable mass-energy generator posited as a direct competitor to conventional energy provision systems), within an 18-month timeframe by the use of the Design-Led Innovation approach: “a process of creating a sustainable competitive advantage by radically changing the customer value proposition” (Bucolo & Matthews 2011).