Mediating Reaction Orthogonality in Polymer and Materials Science.

Selective control of chemical reactions is critical for the proper regulation of processes ranging from intricate biological systems to large scale industrial manufacturing. The progression of synthetic chemistry toward the complexity seen in Nature requires increased control over many concurrent chemical reactions in a non-interfering (orthogonal) fashion. Fortunately, the practically endless pool of synthetic chemical reactions developed to date can often be combined in an orthogonal manner to provide elegant solutions to complex chemical problems. In this review, we first highlight some of the many photochemical reactions that have been applied in orthogonal reaction protocols; the highly selective nature of photochemical reactions makes them well-suited for independent activation in the presence of other reaction components. The application of these orthogonal reactions, especially photochemical reactions, for the synthesis and modification of polymers and polymeric materials is also summarized. Importantly, the use of orthogonal chemical reactions can provide additional opportunities for synthesizing advanced and functional polymeric materials compared to traditional synthetic procedures.

Controlled Synthesis of Block Copolymers by Mechanistic Transformation from Atom Transfer Radical Polymerization to Iniferter Process.

A straightforward transformation protocol combining two distinct living polymerization methods for the controlled synthesis of block copolymers is described. In the first step, bromo-terminated poly(methyl methacrylate) is prepared by atom transfer radical polymerization (ATRP). Then, a bromide end group is substituted with a triphenylmethyl (trityl) functionality under visible light irradiation using dimanganese decacarbonyl (Mn2 (CO)10 ) photochemistry. The resulting polymers with trityl end groups are used as macroiniferter for the polymerization of styrene and tert-butyl acrylate (tBA) to yield desired block copolymers with narrow molecular weight distribution. Moreover, the amphiphilic copolymers with acrylic acid functionalities are obtained by the hydrolyzation of poly(tert-butyl acrylate) containing block copolymers with trifluoroacetic acid.

Block Copolymers by Mechanistic Transformation from PROAD to Iniferter Process.

A facile strategy for synthesizing block copolymers by the combination of two different living polymerization techniques, namely, photoinduced radical oxidation/addition/deactivation (PROAD) and iniferter processes is described. In the first step, PROAD polymerization of isobutyl vinyl ether using bromotriphenylmethane, dimanganese decacarbonyl (Mn2 (CO)10 ), and diphenyliodonium bromide (Ph2 I+ Br- ) is carried out to yield polymers with triphenylmethyl (trityl) end groups. These prepolymers are used as macroiniferters in thermally induced free radical polymerization of vinyl monomers such as methyl methacrylate, tert-butyl acrylate, and styrene, resulting in the formation of corresponding block copolymers free from homopolymers. The precursor polymer and final block copolymers are characterized by 1 H NMR, FT-IR, GPC, and DSC analyses.

Hyperbranched Polymers by Light-Induced Self-Condensing Vinyl Polymerization.

Hyperbranched polymers (HBPs), a unique class of dendritic macromolecules, have received continuous interest from macromolecular scientists due to their inherent properties such as high level of functional terminal units, high solubility, and low viscosity. Despite enormous efforts devoted to the synthesis of HBPs by traditional methods such as single and double monomer strategies involving step-growth polymerization and self-condensing vinyl polymerization (SCVP) processes, there have been limited attempts to employ light-induced processes. Photochemical methods, however, exhibit distinct advantages not characteristically disclosed by traditional ones, such as spatial and temporal control, low energy, and site-specific activation. This review, after a brief summary of the conventional methods, presents the unique features and the key functionalities of the inimers for photoinduced SCVP and strategies for preparing HBPs.

Living Cationic Polymerization of Vinyl Ethers through a Photoinduced Radical Oxidation/Addition/Deactivation Sequence.

A new photoinitiating system for living cationic polymerization of vinyl ethers is reported. In the current approach, visible-light irradiation of dimanganese decacarbonyl (Mn2 (CO)10 ) in the presence of an alkyl bromide results in the formation of carbon-centered radicals. The photochemically generated radicals were then oxidized by diphenyliodonium ions to the corresponding cations. These cations can add vinyl ether monomers, which are then rapidly deactivated by the bromide anions to give α-halide functional end groups. Poly(vinyl ether) chains are then grown through successive photoinduced radical oxidation/addition/deactivation (PROAD) in a controlled manner. The living nature of the system is evaluated through kinetics studies and block copolymer formation.

Hyperbranched Polymers by Type II Photoinitiated Self-Condensing Vinyl Polymerization.

Type II photoinitiated self-condensing vinyl polymerization for the preparation of hyperbranched polymers is explored using 2-hydroxyethyl methacrylate (HEMA) or 2-(dimethylamino)ethyl methacrylate (DMAEMA), and methyl methacrylate as hydrogen donating inimers and comonomer, respectively, in the presence of benzophenone and camphorquinone under UV and visible light. Upon irradiation at the corresponding wavelength, the excited photoinitiator abstracts hydrogen from HEMA or DMAEMA leading to the formation of initiating radicals. Depending on the concentration of inimers, type of the photoinitiator, and irradiation time, hyperbranched polymers with different branching densities and cross-linked polymers are formed.

Nanostructured Amphiphilic Star-Hyperbranched Block Copolymers for Drug Delivery.

A robust drug delivery system based on nanosized amphiphilic star-hyperbranched block copolymer, namely, poly(methyl methacrylate-block-poly(hydroxylethyl methacrylate) (PMMA-b-PHEMA) is described. PMMA-b-PHEMA was prepared by sequential visible light induced self-condensing vinyl polymerization (SCVP) and conventional vinyl polymerization. All of the synthesis and characterization details of the conjugates are reported. To accomplish tumor cell targeting property, initially cell-targeting (arginylglycylaspactic acid; RGD) and penetrating peptides (Cys-TAT) were binding to each other via the well-known EDC/NHS chemistry. Then, the resulting peptide was further incorporated to the surface of the amphiphilic hyperbranched copolymer via a coupling reaction between the thiol (-SH) group of the peptide and the hydroxyl group of copolymer by using N-(p-maleinimidophenyl) isocyanate as a heterolinker. The drug release property and targeting effect of the anticancer drug (doxorobucin; DOX) loaded nanostructures to two different cell lines were evaluated in vitro. U87 and MCF-7 were chosen as integrin αvß3 receptor positive and negative cells for the comparison of the targeting efficiency, respectively. The data showed that drug-loaded copolymers exhibited enhanced cell inhibition toward U87 cells in compared to MCF-7 cells because targeting increased the cytotoxicity of drug-loaded copolymers against integrin αvß3 receptor expressing tumor cells.

Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience.

OBJECTIVES: To evaluate and present the data regarding clinical, laboratory, radiological and the results of molecular genetic analysis of patients with hyperinsulinemic hypoglycemia in our clinics. METHODS: A total of 9 patients with CHI followed at Istanbul Medipol University. Data related to gender, age at presentation, birth weight, gestational age, consanguinity, glucose and insulin levels at diagnosis, treatment modalities, response to treatment, the results of genetic analysis and radiological evaluation were gathered from the files. RESULTS: The oldest age at presentation was 6 months. KATP channel mutation was detected in 55% (n: 5). Diazoxide unresponsiveness was seen in 55% (n: 5). Octreotide was effective in 3 of them. 18F-DOPA PET performed in 4 diazoxide unresponsive patients revealed focal lesion in 3 of them. Spontaneous remission rate was 66% (n:6). All the patients with normal genetic result achieved spontaneous remission. Spontaneous remission was even noted in diazoxide unresponsive patients and in patients with focal lesion on 18F-DOPA PET. CONCLUSIONS: Clinical presentation of patients with congenital hypereinsulinism is heterogeneous. Spontaneous remission rate is quite high even in patients with severe clinical presentation. It is important to develop methods that can predict which patients will have spontaneous remission. Reporting the clinical and laboratory data of each patient is important and will help to guide the management of patients with hyperinsulinemic hypoglycemia.

Protective effect of silymarin on tacrolimus-induced kidney and liver toxicity.

BACKGROUND: Tacrolimus (FK506) is an immunosuppressive agent and has toxic side effects such as nephrotoxicity, hepatotoxicity, and neurotoxicity. In our study, we aimed to investigate the protective effect of silymarin on renal and hepatic toxicity considered to be tacrolimus related. METHODS: In this 6-week experimental study, 46 eight-week-old healthy male rats were used. The groups comprised the Control (healthy rats, n = 6), Tac (tacrolimus 1 mg/kg, n = 8), silymarin 100 mg/kg (SLI 100 mg/kg n = 8), Tac + SLI 100 (tacrolimus 1 mg/kg + SLI 100 n = 8), SLI 200 (SLI 200 mg/kg n = 8), and Tac + SLI 200 (tacrolimus 1 mg/kg + SLI 200 mg/kg n = 8). After 6 weeks, all rats were sacrificed, and the tissue follow-up procedure was performed for kidney and liver tissues, histopathology, and in situ TUNEL analysis. Blood samples were analyzed for the total antioxidant capacity (TAC), total oxidant capacity (TOC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), albumin, total bilirubin, creatine. RESULTS: Histopathological findings of kidney and liver tissue of rats were determined to increase statistically in Tac group compared to SLI 1 00 and SLI 200 groups (P < 0.05). In addition, the Tac + SLI 100 and Tac + SLI 200 groups were found to be statistically similar to the Control group (P > 0.05). The in situ TUNEL method showed that the tacrolimus increased apoptosis while the silymarin decreased it. TOC levels increased statistically in Tac groups compared to silymarin-treated groups (P < 0.05). Although the TAC level was not statistically significant among the experimental groups (P > 0.05), the lowest was measured in the Tac group. The ALT, AST, GGT, total bilirubin, and creatine values were higher in the Tac group than in the silymarin groups (P < 0.05). There was no statistically significant difference between the groups with regard to the albumin level (P > 0.05). CONCLUSION: In our study, we determined that tacrolimus caused damage to kidney and liver tissue. Histopathological, biochemical and apoptotic findings show that silymarin has a protective effect against nephrotoxicity and hepatotoxicity caused by tacrolimus.

A polydiacetylene-based colorimetric sensor as an active use-by date indicator for milk.

Current food date marking tools fail to take into account variables that impact shelf life, leading to food waste and posing human health risks. Herein, we develop a polydiacetylene/zinc oxide (PDA/ZnO) colorimetric sensor that can indicate milk freshness in real time. The PDA/ZnO system is engineered to indicate the freshness of full cream milk by monitoring its pH based on lactic acid concentration, an indicator of bacterial spoilage. The sensitivity is tuned by selection of the diacetylene monomers from which it is composed. Designs constructed from shorter chain diacetylenes are found to undergo chromatic transitions at a lower lactic acid concentration. Two new methods to tune PDA/ZnO sensitivity to lactic acid are explored, including relocation of the diacetylene functional group and lipid doping. A system constructed from 5,7-hexadecadiynoic acid (HDDA) and ZnO can discriminate between fresh (pH 6.8-6.0), spoiling (pH 6.0-4.5), and spoiled milk (pH 4.5-4.0) by a respective blue to purple to red color change. The chromatic stability of the PDA/ZnO sensor in food is studied as previous reports have shown the system to be unstable. We present a new method that stabilizes the nanocomposite by pre-exposure to the food matrix prior to photopolymerization.

Designing with Light: Advanced 2D, 3D, and 4D Materials.

Recent achievements and future opportunities for the design of 2D, 3D, and 4D materials using photochemical reactions are summarized. Light is an attractive stimulus for material design due to its outstanding spatiotemporal control, and its ability to mediate rapid polymerization under moderate reaction temperatures. These features have been significantly enhanced by major advances in light generation/manipulation with light-emitting diodes and optical fiber technologies which now allows for a broad range of cost-effective fabrication protocols. This combination is driving the preparation of sophisticated 2D, 3D, and 4D materials at the nano-, micro-, and macrosize scales. Looking ahead, future challenges and opportunities that will significantly impact the field and help shape the future of light as a versatile and tunable design tool are highlighted.

Polyethylene-g-Polystyrene Copolymers by Combination of ROMP, Mn2(CO)10-Assisted TEMPO Substitution and NMRP.

The synthesis of polyethylene-graft-polystyrene copolymers by a multistep "grafting from" approach is described. In the first step, a bromo-functional polyethylene (PE-Br) was synthesized via ring-opening metathesis polymerization (ROMP) of cis-cyclooctene (COE) and quantitative hydrobromination. Subsequent irradiation of PE-Br under visible light in the presence of dimanganese decacarbonyl (Mn2(CO)10) and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) resulted in the formation of TEMPO-substituted polyethylene (PE-TEMPO). Polystyrene (PS) chains were then grown via nitroxide mediated radical polymerization (NMRP) from the PE-TEMPO precursor to give desired PE-g-PS copolymers in a controlled manner. The intermediates at each step and final graft copolymers were characterized by 1H NMR, FT-IR, GPC, and DSC analyses.

A simple route to synthesis of branched and cross-linked polymers with clickable moieties by photopolymerization.

Lightly branched, hyperbranched and cross-linked polymers with clickable sites were synthesized via a modified version of self-condensing photoinitiated copolymerization of methyl acrylate (MA) with propargyl acrylate (PA). The method is based on the use of a PA monomer containing two polymerizable groups, namely acrylate and propargyl groups with different reactivities in photoinitiated free radical copolymerization with MA.