STUDIES ON THE MOLECULAR STRUCTURE OF WT-12 DERIVATIVE OF PYRAZOLO [3,4-d] - 1,3,2-DIAZAPHOSPHORIN-6-ONE

<正> The title compound was obtained by reaction of 1-phenyl-5-benzy-lamino-pyrazole-4-(N-methyl) carboxamide with p-fluorophenyl phosphorus dichloride and its molecular structure determined by X-ray diffraction method. The crystal is mono-clinic,space group P21/c,with a=11. 874(2),b= 12. 986(2),c=14. 587(2) A ,β= 106. 21(1)°,V=2159. 6A3,Mr = 430. 43(C24H20N4OFP),Z=4, Dx = 1. 324g/cm-3,μ(MoKa) = 1. 53cm-1 ,and F(000) = 896. The atoms in the pyrazolo[3,4-d] - 1,3,2-di-azaphosphorin-6-one are coplanar except the P atom.     

Darstellung,Charakterisierung und Struktur funktionalisierter Fluorphosphaalkene des Typs R3E–P=C(F)NEt2 (R/E = Me/Si,Me/Ge,CF3/Ge,Me/Sn)

Preparation, Characterization, and Structure of Functionalized Fluorophosphaalkenes of the Type R₃E–P=C(F)NEt₂ (R/E = Me/Si, Me/Ge, CF₃/Ge, Me/Sn) P‐functionalized 1‐diethylamino‐1‐fluoro‐2‐phosphaalkenes of the type R₃E–P=C(F)NEt₂ [R/E = Me/Si ( 2 ), Me/Ge ( 3 ), CF₃/Ge ( 4 ), Me/Sn ( 5 )] are prepared by reaction of HP=C(F)NEt₂ ( 1 , E/Z = 18/82) with R₃EX (X = I, Cl) in the presence of triethylamine as base, exclusively as Z‐Isomers. 2–5 are thermolabile, so that only the more stable representatives 2 and 4 can be isolated in pure form and fully characterized. 3 and 5 decompose already at temperatures above –10 °C, but are clearly identified by ¹⁹F and ³¹P NMR‐measurements. The Z configuration is established on the basis of typical NMR data, an X‐ray diffraction analysis of 4 and ab initio calculations for E and Z configurations of the model compound Me₃Si–P=C(F)NMe₂. The relatively stable derivative 2 is used as an educt for reactions with pivaloyl‐, adamantoyl‐, and benzoylchloride, respectively, which by cleavage of the Si–P bond yield the push/pull phosphaalkenes RC(O)–P=C(F)NEt₂ [R = tBu ( 6 ), Ad ( 7 ), Ph ( 8 )], in which π‐delocalization with the P=C double bond occurs both with the lone pair on nitrogen and with the carbonyl group.     

Reduced Endocannabinoid Tone in Saliva of Chronic Orofacial Pain Patients

Background: the endocannabinoid system (ECS) participates in many physiological and pathological processes including pain generation, modulation, and sensation. Its involvement in chronic orofacial pain (OFP) in general, and the reflection of its involvement in OFP in salivary endocannabinoid (eCBs) levels in particular, has not been examined. Objectives: to evaluate the association between salivary (eCBs) levels and chronic OFP. Methods: salivary levels of 2 eCBs, anandamide (AEA), 2-arachidonoylglycerol (2-AG), 2 endocannabinoid-like compoundsN-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed using liquid chromatography/tandem mass spectrometry in 83 chronic OFP patients and 43 pain-free controls. The chronic OFP patients were divided according to diagnosis into musculoskeletal, neurovascular/migraine, and neuropathic pain types. Results: chronic OFP patients had lower levels of OEA (p = 0.02) and 2-AG (p = 0.01). Analyzing specific pain types revealed lower levels of AEA and OEA in the neurovascular group (p = 0.04, 0.02, respectively), and 2-AG in the neuropathic group compared to controls (p = 0.05). No significant differences were found between the musculoskeletal pain group and controls. Higher pain intensity was accompanied by lower levels of AA (p = 0.028), in neuropathic group. Conclusions: lower levels of eCBs were found in the saliva of chronic OFP patients compared to controls, specifically those with neurovascular/migraine, and neuropathic pain. The detection of changes in salivary endocannabinoids levels related to OFP adds a new dimension to our understanding of OFP mechanisms, and may have diagnostic as well as therapeutic implications for pain.     

Establishment of a kinetic model for the intramolecular catalyzed hydrolysis of [18F]‐benzylfluoride containing amino acid analogues by linking experimental and DFT studies

In an earlier publication, we suggested that the faster radiodefluorination kinetics of no‐carrier‐added (S)‐3‐(2‐[¹⁸F]fluoromethyl‐phenyl)‐2‐amino‐propionic acid (2‐[¹⁸F]FMLP), as compared to 4‐[¹⁸F]‐fluoromethyl‐l ‐phenylalanine (4‐[¹⁸F]FMLP), was caused by an intramolecular interaction between the CH₂F group on the 2‐position of the phenyl ring and the ammonium group of the amino acid. As the presence of nonradioactive (S)‐3‐(2‐fluoromethyl‐phenyl)‐2‐amino‐propionic acid (2FMLP) in a concentration up from 10^?6 mol/L reduces considerably the defluorination rate due to the formation of dimers, conventional experimental methods, like spectroscopy, cannot be performed for the study of the hydrolysis in no‐carrier‐added conditions occurring at a concentration range of about 5.0 10^?10 mol/L. In the present study, we aim to provide a proof that supports aforementioned hypothesis as well as to establish a kinetic model and to put forward accompanying rate equations for this hydrolysis reaction by combining ab initio quantum chemical calculations and kinetic data. The calculations of the optimized geometries and the corresponding energies of the reactants involved in the hydrolysis of 2‐[¹⁸F]FMLP and 4‐[¹⁸F]FMLP were performed at the DFT[B3LYP/6‐31⁺⁺G**] level of theory. Interpretation of these data reveals that in 2‐[¹⁸F]FMLP three intramolecular hydrogen bond interactions can be identified that are not present in 4‐[¹⁸F]FMLP. The most important interaction is the one between the amino acid ammonium group and the benzylic fluorine atom, rendering the rupture of the C? F bond much more favorable. These findings align with the experimental data and enabled us to put forward the rate expressions that define the unexpected pseudo–zero‐order defluorination reaction of 2‐[¹⁸F]FMLP at neutral pH. This study also proves that in the development of [¹⁸F]‐benzylfluoride containing tracers present‐day quantum chemical calculations are capable of predicting intramolecular interactions, affecting their reactivity toward hydrolysis at the no‐carrier‐added level. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 705–711, 2012     

Sulfonyl Fluoride‐Based Prosthetic Compounds as Potential 18F Labelling Agents

Nucleophilic incorporation of [¹⁸F]F^? under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to ¹⁸F‐labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4‐formyl‐, 3‐formyl‐, 4‐maleimido‐ and 4‐oxylalkynl‐arylsulfonyl [¹⁸F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[¹⁸F]F/Cs₂CO_3(aq.) in a reaction time of 15 min at room temperature. With the exception of 4‐N‐maleimide‐benzenesulfonyl fluoride ( 3 ), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [¹⁸F]fluorination (1:1:0.8 tBuOH/Cs₂CO_3(aq.)/pyridine) did not negatively affect yields of 3‐formyl‐2,4,6‐trimethylbenzenesulfonyl [¹⁸F]fluoride ( 2 ) and dramatically improved the yields of 4‐(prop‐2‐ynyloxy)benzenesulfonyl [¹⁸F]fluoride ( 4 ). The N‐arylsulfonyl‐4‐dimethylaminopyridinium derivative of 4 ( 14 ) can be prepared and incorporates ¹⁸F efficiently in solutions of 100 % aqueous Cs₂CO₃ (10 mg mL^?1). As proof‐of‐principle, [¹⁸F] 2 was synthesised in a preparative fashion [88(±8) % decay corrected (n=6) from start‐of‐synthesis] and used to radioactively label an oxyamino‐modified bombesin(6–14) analogue [35(±6) % decay corrected (n=4) from start‐of‐synthesis]. Total preparation time was 105–109 min from start‐of‐synthesis. Although the ¹⁸F‐peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature ¹⁸F labelling strategy.     

Nylon 610/functionalized multiwalled carbon nanotube composite prepared from in‐situ interfacial polymerization

Pristine multiwalled carbon nanotubes (P‐MWNTs) were functionalized with 4‐chlorobenzoic acid via “direct” Friedel‐Crafts acylation in polyphosphoric acid (PPA)/phosphorous pentoxide (P₂O₅) medium. The resultant 4‐chlorobenzoyl‐functionalized MWNTs (F‐MWNTs) were soluble in chlorinated solvents such as dichloromethane, chloroform, and carbon tetrachloride. A large scale of nylon 610/F‐MWNT composite could be conveniently prepared by in situ interfacial polymerization of 1, 6‐hexamethylenediamine (HMDA) in an aqueous phase, and sebacoyl chloride with F‐MWNTs in an organic phase. Similarly, nylon 610/P‐MWNT composite was also prepared for comparison. The state of F‐MWNTs dispersion in nylon 610 matrix was distinctively better than that of P‐MWNTs, which could be clearly discerned by both naked eye and scanning electron microcopy (SEM). As a result, the tensile strength of nylon 610/F‐MWNT composite was 4.9‐fold higher than that of nylon 610/P‐MWNT composite. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6041–6050, 2008     

A General Copper‐Mediated Nucleophilic 18F Fluorination of Arenes

Molecules labeled with fluorine‐18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (S_NAr) with [¹⁸F]F^?. In the ideal case, the ¹⁸F fluorination of these substrates would be performed through reaction of [¹⁸F]KF with shelf‐stable readily available precursors using a broadly applicable method suitable for automation. Herein, we describe the realization of these requirements with the production of ¹⁸F arenes from pinacol‐derived aryl boronic esters (arylBPin) upon treatment with [¹⁸F]KF/K₂₂₂ and [Cu(OTf)₂(py)₄] (OTf=trifluoromethanesulfonate, py=pyridine). This method tolerates electron‐poor and electron‐rich arenes and various functional groups, and allows access to 6‐[¹⁸F]fluoro‐L ‐DOPA, 6‐[¹⁸F]fluoro‐m‐tyrosine, and the translocator protein (TSPO) PET ligand [¹⁸F]DAA1106.     

Synthesis of para‐[18F]Fluorofenbufen Octylamide for PET Imaging of Brain Tumors

Glioma is a brain tumor associated with a poor therapeutic outcome with an average life expectancy of 14 months. Cyclooxygenase‐2 (COX‐2) expression is associated with the progression of the tumor and is considered a therapeutic target of chemo agents. Para‐[¹⁸F]Fluorofenbufen octylamide ([¹⁸F]FFOA) was obtained with the radiochemical yield of 16% and specific activity of 4 GBq/μmol, and the IC₅₀ values of COX‐1 and COX‐2 were 26.5 and 32.7 μM, respectively. The stability of cold FFOA in plasma was significantly improved with a half‐life of 30 min, and the uptake ratio of [¹⁸F]FFOA in rats with brain tumor was 1.5 as determined from accumulation of 3.9% injection dose (ID/g) in the brain tumor and 2.5% ID/g in the brain. [¹⁸F]FFOA with COX‐2 micromolar affinity can be used to differentiate between brain tumor and normal region.     

Selective synthesis of monoaryl substituted porphyrins

A synthetic route to meso-monoarylporphyrins using a MacDonald-type 2 + 2 condensation is described. In this method a bisformyl substituted dipyrrylmethane is treated with a biscarboxydipyrrylmethane. The 5-aryldipyrrylmethanes 15, 25 and 27 were obtained by condensation of the corresponding pyrroles 18, 28 and 29 respectively with benzaldehyde in presence of p-toluenesulfonic acid.     

Pure blue electroluminescent poly(aryl ether)s with dopant–host systems

A series of novel arylene ether polymers (P5F‐BCzVFs) containing both pentafluorene (5F) and distyrylarylene derivative (BCzVF) units in the side chains for efficient pure blue light emission were prepared by a facile, metal‐free condensation polymerization. The emission spectra indicated that color tuning could be achieved through efficient Förster energy transfer from the deep‐blue 5F host to the pure‐blue BCzVF dopant. Single‐layer polymer light‐emitting diodes (PLEDs) based on P5F‐BCzVFs (ITO/(PEDOT:PSS)/polymer/Ca/Al) exhibited voltage‐independent and stable pure blue emission with a Commission International de L'Eclairage (CIE) coordinate of (0.15, 0.15), a maximum brightness of 3576 cd/m², and a maximum luminous efficiencies of 2.15 cd/A, respectively. As most polymers with dopant‐host systems, the luminous efficiencies of all P5F‐BCzVFs surpassed that of the host‐only polymer (P5F), due to the energy transfer and charge trapping from the host to the dopant. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Crosslinkable high dielectric constant polymer dielectrics for low voltage organic field‐effect transistor memory devices

I n this study, we successfully synthesized water/methanol soluble random copolymers with a high dielectric constant, poly(n‐(hydroxymethyl) acrylamide‐co‐5‐(9‐(5‐(diethylamino)pentyl)?2‐(4‐vinylphenyl)?9H‐fluorene(P(NMA‐co‐F6NSt)), which contained chemical crosslinkable segment (NMA) and hole trapping building block (F6NSt). The feeding molar ratios of two monomers (NMA:F6NSt) were set as 100:0, 95:5, 80:20, and 67:33 for the copolymers of P1 , P2 , P3, and P4 , respectively. The crosslinked P(NMA‐co‐F6NSt) thin film could serve as both dielectric and charge storage layers in organic field‐effect transistor (OFET) memory device and exhibited high k (i.e., 4.91–6.47) characteristics, leading to a low voltage operation and a small power consumption. Devices based on the P1 ‐ P4 dielectrics showed excellent insulating properties and good charge storage performance under a low operating voltage in a range of ±5V because of tightly network structures and well‐dispersed trapping cites. In particular, P3 ‐based memory device exhibited a large memory window of 4.13 V with stable data retention stability over 10⁴ s, a large on/off ratio of 10⁴, and good endurance characteristics as high as 200 cycles. The above results suggested that a high‐performance OFET memory device could be facilely achieved using the novel crosslinkable high‐k copolymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3224–3236     

Efficient PKC inhibitor screening achieved using a quantitative CE‐LIF assay

An assay for protein kinase C delta (PKCδ) activity based on the quantification of a synthetic substrate using capillary electrophoresis with laser‐induced fluorescence detection was developed. The peptides labeled with fluorescein isothiocyanate F‐ERK (where ERK is extracellular signal‐regulated kinase) and the phosphorylated form, P‐F‐ERK, were utilized for the method development and validation. The migration time of F‐ERK and P‐F‐ERK were 6.3 ± 0.1 and 8.7 ± 0.2 min, respectively. LOD and LOQ values of F‐ERK were 2 and 6 ng/mL and those of P‐F‐ERK were 4 and 12 ng/mL. The correlation coefficients obtained from two standard curves were approximately 0.99. The reproducibility and accuracy of the method for F‐ERK ranged 1.5–4.7 and 86–109%, respectively, and those for P‐F‐ERK were 1.6–6.1 and 93–109%, respectively. The activity of PKCδ was studied in vitro using the human gastric cancer cell line MKN‐1. The use of PKCδ inhibitor candidates, including G?6983, bisindolylmaleimide II, staurosporine, and rottlerin in the assay resulted in IC₅₀ values of 50 nM, 15 nM, 795 nM, and 4 μM, respectively. Comparison of our assay with a commercial PKC kit revealed that our assay is more adaptable to differing enzyme isoforms. This method has potential for high throughput screening for kinase inhibitors as part of a drug discovery program.     

Homogeneous nucleophilic radiofluorination and fluorination with phosphazene hydrofluorides

A series of phosphazenium hydrofluorides, P(1)(tBu)·[(18/19)F]HF, P(1)(tOct)·[(18/19)F]HF, P(2)(Et)·[(18/19)F]HF, and P(4)(tBu)·[(18/19)F]HF, was synthesized. The radioactive phosphazenium [(18)F]hydrofluorides were obtained by the one-step formation and trapping of gaseous [(18)F]HF with the respective phosphazene bases. The [(19)F] isotopomers were prepared from the corresponding phosphazene bases and Et(3)N·3HF. Under the design of experiment (DoE)-optimized conditions, P(2)(Et)·HF and P(4)(tBu)·HF fluorinated alkyl chlorides, bromides, and pseudohalides in 76-98% yield, but gave lower yields with iodides and electron-deficient arenes. DoE models showed that fluorination can be performed in glass vessels, and that the reactivity of P(2)(Et)·HF and P(4)(tBu)·HF is dominated by solvent polarity but is insensitive to water to at least 2 equiv. In contrast, P(1)(tBu)·HF and P(1)(tOct)·HF were unstable towards autofluorolysis. DFT calculations were performed to rationalize this finding in terms of diminished steric bulk, higher Parr's electrophilicity, and chemical hardness of P(1)(R)H(+). The corresponding radiofluorination reaction gave no valid DoE model but displayed similar substrate scope. High specific activity and excellent radiochemical yields with various pseudohalides (81-91%) suggest that the proposed radiofluorination methodology can complement the current [(18)F]KF/Kryptofix methods, particularly in the areas for which nonpolar reaction conditions are required.     

Development of a 18F‐Labeled Tetrazine with Favorable Pharmacokinetics for Bioorthogonal PET Imaging

A low‐molecular‐weight ¹⁸F‐labeled tetrazine derivative was developed as a highly versatile tool for bioorthogonal PET imaging. Prosthetic groups and undesired carrying of ¹⁸F through additional steps were evaded by direct ¹⁸F‐fluorination of an appropriate tetrazine precursor. Reaction kinetics of the cycloaddition with trans‐cyclooctenes were investigated by applying quantum chemical calculations and stopped‐flow measurements in human plasma; the results indicated that the labeled tetrazine is suitable as a bioorthogonal probe for the imaging of dienophile‐tagged (bio)molecules. In vitro and in vivo investigations revealed high stability and PET/MRI in mice showed fast homogeneous biodistribution of the ¹⁸F‐labeled tetrazine that also passes the blood–brain barrier. An in vivo click experiment confirmed the bioorthogonal behavior of this novel tetrazine probe. Due to favorable chemical and pharmacokinetic properties this bioorthogonal agent should find application in bioimaging and biomedical research.     

A Resin‐Linker‐Vector Approach to Radiopharmaceuticals Containing 18F: Application in the Synthesis of O‐(2‐[18F]‐Fluoroethyl)‐L‐tyrosine

A Resin‐linker‐vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide ¹⁸F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene‐bound arylsulfonate linker with [¹⁸F]‐fluoride ion. Three model linker‐vector molecules 7 a – c containing different alkyl spacer groups were assembled in solution from (4‐chlorosulfonylphenyl)alkanoate esters, exploiting a lipase‐catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker‐vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8 a – c with acetate, butyrate and hexanoate spacers, which were characterised by using magic‐angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8 a , b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4‐fluorobutyl)phenylcarbamic acid tert‐butyl ester ( 9 ) in NMR kinetic studies and gave superior radiochemical yields (RCY≈60 %) of the ¹⁸F‐labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O‐(2‐[¹⁸F]‐fluoroethyl)‐L ‐tyrosine ([¹⁸F]‐FET), delivering protected [¹⁸F]‐FET in >90 % RCY. Acid deprotection gave [¹⁸F]‐FET in an overall RCY of 41 % from the RLV.     

Synthesis and Evaluation of [18F]‐Ammonium BODIPY Dyes as Potential Positron Emission Tomography Agents for Myocardial Perfusion Imaging

Recently, we demonstrated the potential of a [¹⁸F]‐trimethylammonium BODIPY dye for cardiac imaging. This is the first example of the use of the [¹⁸F]‐ammonium BODIPY dye for positron emission tomography (PET) myocardial perfusion imaging (MPI). In this report, we extend our study to other ammonium BODIPY dyes with different nitrogen substituents. These novel ammonium BODIPY dyes were successfully prepared and radiolabeled by the SnCl₄‐assisted ¹⁸F–¹⁹F isotopic exchange method. The microPET results and the biodistribution data reveal that nitrogen substituent changes have a significant effect on the in vivo and pharmacological properties of the tracers. Of the novel [¹⁸F]‐ammonium BODIPY dyes prepared in this work, the [¹⁸F]‐dimethylethylammonium BODIPY is superior in terms of myocardium uptake and PET imaging contrast. These results support our hypothesis that the ammonium BODIPY dyes have a great potential for use as PET/optical dual‐modality MPI probes.     

Untersuchungen zur Bildung multifunktioneller 1,2‐Bis(tritylierter) Diphosphin‐Monoxide

Studies on the Formation of Multifunctional 1,2‐Bis(tritylated) Diphosphine Monoxides The products formed in the systems Ph₃CPH(:O) X /Ph₃CP( Y )Cl/NEt₃ with X = F, H, OH and Y = Cl, H, TMG (= N,N,N′,N′‐tetramethylguanidinyl) are discussed. In the case of the systems X =F/ Y =Cl, X =F/ Y =H, and X = Y =H the diphosphine monoxides 4 a , 5 a and 13 a were formed, while in the case of X =H/ Y =Cl, instead of the expected diphosphine monoxide 14 , a mixture of 13 a and of the POP compound 16 (molar ratio ca. 2 : 1) was observed. Treatment of 4 a with N,N,N′,N′‐tetramethylguanidine (= HTMG) led to the diphosphine monoxide, 7 a whereas its tautomer 7 b was formed, when Ph₃CP(TMG)Cl 6 reacted with Ph₃CPH(:O)F 1 . The conversion of one tautomer, 7 a or 7 b , into the other was not observed. On the other hand Cl₂P–PCPh₃(:O)F 8 a , formed as an intermediate in the reaction of 4 a with PCl₅, spontaneously rearranged to give Ph₃CPClF 9 and P(:O)Cl₃ as the final products. Surprisingly, oxidation of the σ³(P)‐atom in 4 a , 5 a and 13 a was impossible with H₂O₂ · (O:)C(NH₂)₂ as the oxidizing agent. The diphosphite 19 showed no rearrangement to the tautomeric diphosphine dioxide 18 , but oxidation to 20 was possible. All the products containing two asymmetrically substituted phosphorus atoms were obtained as diastereomeric mixtures of the meso and racemic form, as proved by ³¹P NMR spectroscopy.     

Synthesis of 18F‐Labelled β‐Lactams by Using the Kinugasa Reaction

Owing to their broad spectrum of biological activities and low toxicity, β‐lactams are attractive lead structures for the design of novel molecular probes. However, the synthesis of positron emission tomography (PET)‐isotope‐labelled β‐lactams has not yet been reported. Herein, we describe the simple preparation of radiofluorinated β‐lactams by using the fast Kinugasa reaction between ¹⁸F‐labelled nitrone [¹⁸F]‐ 1 and alkynes of different reactivity. Additionally, ¹⁸F‐labelled fused β‐lactams were obtained through the reaction of a cyclic nitrone 7 with radiofluorinated alkynes [¹⁸F]‐ 6 a , b . Radiochemical yields of the Kinugasa reaction products could be significantly increased by the use of different Cu^I ligands, which additionally allowed a reduction in the amount of precursor and/or reaction time. Model radiofluorinated β‐lactam‐peptide and protein conjugates ([¹⁸F]‐ 10 and ¹⁸F‐labelled BSA conjugate) were efficiently obtained in high yield under mild conditions (aq. MeCN, ambient temperature) within a short reaction time, demonstrating the suitability of the developed method for radiolabelling of sensitive molecules such as biopolymers.     

A new benzoquinone-bridged porphyrin

The bridged porphyrin 6 was prepared via the bis(dipyrrylmethane) compounds 3, 4 and 5, by demethylation of 6 and oxidation the benzoquinone/porphyrin system 2 was obtained. The strong fluorescence quenching of 2, as compared to 6, is explained on the basis of an electron-transfer from porphyrin to quinone in the S₁ state.