Synthesis of hexasubstituted boron-dipyrromethenes having a different combination of substituents

A series of sterically crowded, mixed hexasubstituted BODIPYs containing two different types of substituents on the pyrrole carbons have been synthesized in high yields by a stepwise approach. The mixed BODIPYs were synthesized by bromination of BODIPYs followed by coupling with appropriate boronic acids under Suzuki coupling conditions. This approach has allowed the introduction of two different types of methyl/aryl substituents at the designated positions of the BODIPY core. All the hexasubstituted BODIPYs are readily soluble in common organic solvents and have been characterized by various spectral and electrochemical techniques. The spectral studies indicated that the presence of mixed methyl/aryl substituents on the BODIPY core significantly alters the electronic properties, and the electrochemical studies revealed that the BODIPYs are stable under redox conditions

Synthesis of Conjugated BODIPYs via the Wittig Reaction

A Wittig reaction was employed to synthesize conjugated BODIPYs in high yields by treating formylated BODIPYs with alkyl/aryl ylides under simple room temperature conditions. Treatment of 3,5-diformyl BODIPYs or α-formyl 3-pyrrolyl BODIPY with different alkyl/aryl ylides in CH₂Cl₂ at room temperature for 2 h followed by straightforward column chromatographic purification on silica afforded conjugated BODIPYs in ∼65–90% yields. This is an alternate method to Knoevenagel and Heck reactions which have been used to synthesize such conjugated BODIPYs. The method works very efficiently, and we prepared 12 substituted BODIPYs including cholesterol-substituted BODIPYs to demonstrate the versatility of the reaction. The spectral, electrochemical, and fluorescence properties of these conjugated BODIPYs are also described

Functionalized boron-dipyrromethenes and their applications

Boron-dipyrromethenes/BF2-dipyrrins (BODIPYs) are highly fluorescent dyes with a wide range of applications in various fields because of their attractive photophysical properties. One of the salient features of BODIPYs is that the properties of the BODIPY can be fine-tuned at will by selectively introducing the substituent(s) at the desired location(s) of the BODIPY. The BODIPYs have several potential sites where the functional groups can be introduced and the functionalized BODIPYs can be used as building blocks to synthesize the desired BODIPY derivatives with interesting features. In this review, we presented the synthesis of different types of functionalized BODIPYs where the functional group(s) were introduced directly at the meso-carbon, at the pyrrole carbons of the BODIPY core as well as at the boron center and discussed their applications toward synthesis of simple substituted BODIPYs to complex BODIPY based systems

Lewis acid assisted decomplexation of F-BODIPYs to dipyrrins

A simple synthetic route was developed for the decomplexation of F-BODIPYs (fluorine-substituted boron–dipyrromethenes) to afford dipyrrins in high yields. This was achieved by treating the F-BODIPYs with different Lewis acids such as ZrCl4, TiCl4, AlCl3, Sc(OTf)3 or SnCl4 in CH3CN/CH3OH under refluxing conditions. This synthetic strategy was efficient for different types of F-BODIPYs such as meso-aryl-substituted BODIPYs, 3-pyrrolyl BODIPYs, functionalized 3-pyrrolyl BODIPYs, π-extended pyrrolyl BODIPYs, sterically crowded BODIPYs and the BF2 complex of 25-oxasmaragdyrin

Halogenated boron-dipyrromethenes: synthesis, properties and applications

Boron-dipyrromethene dyes (BODIPYs) containing halogens at pyrrole carbons are very useful synthons for the synthesis of a variety of BOIDPYs for a wide range of applications. Among the functional groups, halogens are the functional groups which can be regiospecifically introduced at any desired pyrrole carbon of the BODIPY framework by adopting appropriate synthetic strategies. The halogenated BODIPYs can undergo facile nucleophilic substitution reactions to prepare several interesting BODIPY based compounds. This review describes the synthesis, properties and potential applications of halogenated BODIPYs containing one to six halogens at the pyrrole carbons of the BODIPY core as well as properties and applications of some of the substituted BODIPYs derived from halogenated BODIPYs

Constitutive Optimized Production of Streptokinase in Saccharomyces cerevisiae Utilizing Glyceraldehyde 3-Phosphate Dehydrogenase Promoter of Pichia pastoris

A novel expression vector constructed from genes of Pichia pastoris was applied for heterologous gene expression in Saccharomyces cerevisiae. Recombinant streptokinase (SK) was synthesized by cloning the region encoding mature SK under the control of glyceraldehyde 3-phosphate dehydrogenase (GAP) promoter of Pichia pastoris in Saccharomyces cerevisiae. SK was intracellularly expressed constitutively, as evidenced by lyticase-nitroanilide and caseinolytic assays. The functional activity was confirmed by plasminogen activation assay and in vitro clot lysis assay. Stability and absence of toxicity to the host with the recombinant expression vector as evidenced by southern analysis and growth profile indicate the application of this expression system for large-scale production of SK. Two-stage statistical approach, Plackett-Burman (PB) design and response surface methodology (RSM) was used for SK production medium optimization. In the first stage, carbon and organic nitrogen sources were qualitatively screened by PB design and in the second stage there was quantitative optimization of four process variables, yeast extract, dextrose, pH, and temperature, by RSM. PB design resulted in dextrose and peptone as best carbon and nitrogen sources for SK production. RSM method, proved as an efficient technique for optimizing process conditions which resulted in 110% increase in SK production, 2352 IU/mL, than for unoptimized conditions

Vectorial Charge Separation and Selective Triplet-State Formation during Charge Recombination in a Pyrrolyl-Bridged BODIPY–Fullerene Dyad

A donor–acceptor dyad composed of BF₂-chelated dipyrromethene (BDP or BODIPY) and fullerene connected with a pyrrole ring spacer, <b>1</b>, has been newly synthesized and characterized. Because of α-carbon substitution and extended conjugation offered by the pyrrole ring, the optical absorbance and emission spectra of BDP macrocycle were found to be red-shifted significantly. Electrochemical studies provided information on the redox potentials while computational studies performed at the B3LYP/6-31G* level yielded an optimized geometry of the dyad that was close to that reported earlier for a BDP-C₆₀ dyad covalently connected through the central boron atom, <b>2</b>. The HOMO of the dyad was found to be on the BDP macrocycle, extended over the pyrrole bridging group, a property that is expected to facilitate electronic communication between the BDP and fullerene entities. The established energy level diagram using spectral, redox, and optimized structural results predicted possibility of photoinduced electron transfer in both benzonitrile and toluene, representing polar and nonpolar solvents. However, such energy diagram suggested different routes for the charge recombination processes, that is, direct relaxation of the radical ion-pair in polar solvent while populating the triplet level of the sensitizer (³BDP* or ³C₆₀*) in nonpolar solvent. Proof for charge separation and solvent dependent charge recombination processes were established from studies involving femto- and nanosecond pump–probe spectroscopy. The measured rate of charge separation, <i>k</i>_CS, for <b>1</b> was higher in both solvents compared to the earlier reported values for <b>2</b> due to electronically well-communicating pyrrole spacer. The charge recombination in toluene populated ³BDP* as an intermediate step while in benzonitrile it yielded directly ground state of the dyad. The present findings reveal the significance of pyrrole spacer between the donor and acceptor to facilitate charge separation and solvent polarity dependent charge recombination processes

Accuracy of Dexcom G6 Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients With Diabetes

OBJECTIVE: Advances in continuous glucose monitoring (CGM) have transformed ambulatory diabetes management. Until recently, inpatient use of CGM has remained investigational, with limited data on its accuracy in the hospital setting. RESEARCH DESIGN AND METHODS: To analyze the accuracy of Dexcom G6, we compared retrospective matched-pair CGM and capillary point-of-care (POC) glucose data from three inpatient CGM studies (two interventional and one observational) in general medicine and surgery patients with diabetes treated with insulin. Analysis of accuracy metrics included mean absolute relative difference (MARD), median absolute relative difference (ARD), and proportion of CGM values within 15, 20, and 30% or 15, 20, and 30 mg/dL of POC reference values for blood glucose >100 mg/dL or ≤100 mg/dL, respectively (% 15/15, % 20/20, % 30/30). Clinical reliability was assessed with Clarke error grid (CEG) analyses. RESULTS: A total of 218 patients were included (96% with type 2 diabetes) with a mean age of 60.6 ± 12 years. The overall MARD (n = 4,067 matched glucose pairs) was 12.8%, and median ARD was 10.1% (interquartile range 4.6, 17.6]. The proportions of readings meeting % 15/15, % 20/20, and % 30/30 criteria were 68.7, 81.7, and 93.8%, respectively. CEG analysis showed 98.7% of all values in zones A and B. MARD and median ARD were higher in the case of hypoglycemia (<70 mg/dL) and severe anemia (hemoglobin <7 g/dL). CONCLUSIONS: Our results indicate that CGM technology is a reliable tool for hospital use and may help improve glucose monitoring in non-critically ill hospitalized patients with diabetes