Use of 111In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

The present study was designed to evaluate the potential of labeled low‐density lipoprotein with ¹¹¹In using a lipid chelating agent (bis(stearylamide) of diethylenetriaminepentaacetic acid: L) to detect pancreatic tumors and melanoma in mice by gamma‐scintigraphy. We compare the biodistribution of radioactivity and scintigraphic images in nude mice heterotransplanted with human cancerous pancreatic duct cells (Capan‐1) and in mice transplanted with murine tumor cells (B16 melanoma). Biodistribution studies showed that radioactivity was twice as high in the Capan‐1 xenograft after injection of the radiolabel than after injection of radiometal alone, and 34‐fold higher in the B16 tumor. On gamma‐scintigraphic imaging, the Capan‐1 tumor was just visible, whereas the B16 melanoma was clearly imaged. The lack of contrast of the Capan‐1 tumor compared with the B16 melanoma could be due to a poor vascularization. Copyright © 2003 John Wiley & Sons, Ltd.     

Luminescence Tuning and White‐Light Emission of Co‐doped Ln–Cd–Organic Frameworks

Four new three‐dimensional isostructural lanthanide–cadmium metal–organic frameworks (Ln–Cd MOFs), [LnCd₂(imdc)₂(Ac)(H₂O)₂]?H₂O (Ln=Pr ( 1 ), Eu ( 2 ), Gd ( 3 ), and Tb ( 4 ); H₃imdc=4,5‐imidazoledicarboxylic acid; Ac=acetate), have been synthesized under hydrothermal conditions and characterized by IR, elemental analyses, inductively coupled plasma (ICP) analysis, and X‐ray diffraction. Single‐crystal X‐ray diffraction shows that two Ln^III ions are surrounded by four Cd^II ions to form a heteronuclear building block. The blocks are further linked to form 3D Ln–Cd MOFs by the bridging imdc^3? ligand. Furthermore, the left‐ and right‐handed helices array alternatively in the lattice. Eu–Cd and Tb–Cd MOFs can emit characteristic red light with the Eu^III ion and green light with the Tb^III ion, respectively, while both Gd–Cd and Pr–Cd MOFs generate blue emission when they are excited. Different concentrations of Eu³⁺ and Tb³⁺ ions were co‐doped into Gd–Cd/Pr–Cd MOFs, and tunable luminescence from yellow to white was achieved. White‐light emission was obtained successfully by adjusting the excitation wavelength or the co‐doping ratio of the co‐doped Gd–Cd and Pr–Cd MOFs. These results show that the relative emission intensity of white light for Gd–Cd:Eu³⁺,Tb³⁺ MOFs is stronger than that of Pr–Cd:Eu³⁺,Tb³⁺ MOFs, which implies that the Gd complex is a better matrix than the Pr complex to obtain white‐light emission materials.     

New hydrophobic L‐amino acid salts: maleates of L‐leucine,L‐isoleucine and L‐norvaline

Crystals of maleates of three amino acids with hydrophobic side chains [L‐leucenium hydrogen maleate, C₆H₁₄NO₂⁺·C₄H₃O₄⁻, (I), L‐isoleucenium hydrogen maleate hemihydrate, C₆H₁₄NO₂⁺·C₄H₃O₄⁻·0.5H₂O, (II), and L‐norvalinium hydrogen maleate–L‐norvaline (1/1), C₅H₁₁NO₂⁺·C₄H₃O₄⁻·C₅H₁₂NO₂, (III)], were obtained. The new structures contain C₂²(12) chains, or variants thereof, that are a common feature in the crystal structures of amino acid maleates. The L‐leucenium salt is remarkable due to a large number of symmetrically non‐equivalent units (Z′ = 3). The L‐isoleucenium salt is a hydrate despite the fact that L‐isoleucine is a nonpolar hydrophobic amino acid (previously known amino acid maleates formed hydrates only with lysine and histidine, which are polar and hydrophilic). The L‐norvalinium salt provides the first example where the dimeric cation L‐Nva...L‐NvaH⁺ was observed. All three compounds have layered noncentrosymmetric structures. Preliminary tests have shown the presence of the second harmonic generation (SGH) effect for all three compounds.     

Superfine Magnetic Resonance Imaging of the Cerebrovasculature Using Self‐Assembled Branched Polyethylene Glycol–Gd Contrast Agent

Magnetic resonance angiography is an attractive method for the visualization of the cerebrovasculature, but small‐sized vessels are hard to visualize with the current clinically approved agents. In this study, a polymeric contrast agent for the superfine imaging of the cerebrovasculature is presented. Eight‐arm polyethylene glycol with a molecular weight of ≈17 000 Da conjugated with a Gd chelate and fluorescein (F‐8‐arm PEG‐Gd) is used. The relaxivity rate is 9.3 × 10⁻³m ⁻¹ s⁻¹, which is threefold higher than that of free Gd chelate. Light scattering analysis reveals that F‐8‐arm PEG‐Gd is formed by self‐assembly. When the F‐8‐arm PEG‐Gd is intravenously injected, cerebrovasculature as small as 100 µm in diameter is clearly visualized. However, signals are not enhanced when Gd chelate and Gd chelate‐conjugated 8‐arm PEG are injected. Furthermore, small vasculature around infarct region in rat stroke model can be visualized. These results suggest that F‐8‐arm PEG‐Gd enhances the MR imaging of cerebrovasculature.     

L‐Argininium phosphite – a new candidate for NLO materials

In order to investigate the possibility of salt formation in the L‐Arg–H₃PO₃–H₂O system, single crystals of L‐argininium phosphite, C₆H₁₅N₄O₂⁺·H₂PO₃⁻, were prepared by evaporation of an aqueous solution containing equimolar quantities of L‐arginine and phosphorous acid. The asymmetric unit contains one L‐argininium(+) cation and one phosphite [HPO₂(OH)]⁻ anion. The phosphite anions form chains parallel to [010] by O—H...O hydrogen bonding, with an O...O distance of 2.630 (3) Å. The protonated amine and guanidyl groups of the L‐argininium(+) cations form N—H...O hydrogen bonds with the carboxylate groups and anions. The IR and Raman spectra are discussed in relation to the crystal structure. The salt displays nonlinear optical (NLO) properties. Another salt was obtained from a solution with a 1:2 molar ratio of components, but was characterized by vibrational spectra only.     

Electrochemical Behavior and Determination of L‐Tyrosine at Single‐walled Carbon Nanotubes Modified Glassy Carbon Electrode

Based on single‐walled carbon nanotubes (SWCNTs) modified glassy carbon electrode (GCE/SWCNTs), a novel method was presented for the determination of L ‐tyrosine. The GCE/SWCNTs exhibited remarkable catalytic and enhanced effects on the oxidation of L ‐tyrosine. In 0.10 mol/L citric acid‐sodium citrate buffer solution, the oxidation potential of L ‐tyrosine shifted negatively from +1.23 V at bare GCE to +0.76 V at GCE/SWCNTs. Under the optimized experimental conditions, the linear range of the modified electrode to the concentration of L ‐tyrosine was 5.0×10^?6–2.0×10^?5 mol/L (R₁=0.9952) and 2.7×10^?5–2.6×10^?4 mol/L (R₂=0.9998) with a detection limit of 9.3×10^?8 mol/L. The kinetic parameters such as α (charge transfer coefficient) and D (diffusion coefficient) were evaluated to be 0.66, 9.82×10^?5 cm² s^?1, respectively. And the electrochemical mechanism of L ‐tyrosine was also discussed.     

Dissociation Kinetics of Open‐Chain and Macrocyclic Gadolinium(III)‐Aminopolycarboxylate Complexes Related to Magnetic Resonance Imaging: Catalytic Effect of Endogenous Ligands

The kinetics of the metal exchange reactions between open‐chain Gd(DTPA)^2? and Gd(DTPA‐BMA), macrocyclic Gd(DOTA)^? and Gd(HP‐DO3A) complexes, and Cu²⁺ ions were investigated in the presence of endogenous citrate, phosphate, carbonate and histidinate ligands in the pH range 6–8 in NaCl (0.15 M ) at 25 °C. The rates of the exchange reactions of Gd(DTPA)^2? and Gd(DTPA‐BMA) are independent of the Cu²⁺ concentration in the presence of citrate and the reactions occur via the dissociation of Gd³⁺ complexes catalyzed by the citrate ions. The HCO₃^?/CO₃^2? and H₂PO₄^? ions also catalyze the dissociation of complexes. The rates of the dissociation of Gd(DTPA‐BMA), catalyzed by the endogenous ligands, are about two orders of magnitude higher than those of the Gd(DTPA)^2?. In fact near to physiological conditions the bicarbonate and carbonate ions show the largest catalytic effect, that significantly increase the dissociation rate of Gd(DTPA‐BMA) and make the higher pH values (when the carbonate ion concentration is higher) a risk‐factor for the dissociation of complexes in body fluids. The exchange reactions of Gd(DOTA)^? and Gd(HP‐DO3A) with Cu²⁺ occur through the proton assisted dissociation of complexes in the pH range 3.5–5 and the endogenous ligands do not affect the dissociation rates of complexes. More insights into the interaction scheme between Gd(DTPA‐BMA) and Gd(DTPA)^2? and endogenous ligands have been obtained by acquiring the ¹³C NMR spectra of the corresponding diamagnetic Y(III)‐complexes, indicating the increase of the rates of the intramolecular rearrangements in the presence of carbonate and citrate ions. The herein reported results may have implications in the understanding of the etiology of nephrogenic systemic fibrosis, a rare disease that has been associated to the administration of Gd‐containing agents to patients with impaired renal function.     

Synthesis,cytotoxicity and anti‐metastatic properties of new pyridyl–thiazole arene ruthenium(II) complexes

A series of novel ruthenium(II)–cymene complexes ( 1 – 8 ) containing substituted pyridyl–thiazole ligands, [Ru(η⁶‐p‐cymene)(L)Cl]Cl (L = N,N‐chelating derivatives), have been synthesized and characterized using elemental analysis, infrared, ¹H NMR and ¹³C NMR spectroscopies and mass spectrometry. All these complexes not only display marked cytotoxicity in vitro against three different human cancer cell lines (HeLa, A549 and MDA‐MB‐231), but also exhibit promising anti‐metastatic activity at sub‐cytotoxic concentrations. Cell cycle analysis shows that the ruthenium(II) complex‐induced growth inhibition was mainly caused by S‐phase cell cycle arrest. Further protein level analysis suggests that compound 5 may exert antitumor activity via a p53‐independent mechanism.     

Synthese und Koordinationsverhalten neuer Schiffscher Basen aus 3‐Formylacetylaceton und natürlichen L‐Aminosäuren

Three novel chiral Schiff Base ligands (H₂L) were prepared from the condensation reaction of 3‐formyl acetylacetone with the amino acids L ‐alanine, L ‐phenylalanine, and L ‐threonine. X‐ray single crystal analyses revealed that the Schiff Base compounds exist as enamine tautomers in the solid state. The molecular structure of the compounds is stabilized by an intramolecular hydrogen bridge between the enamine NH function and a carbonyl oxygen atom of the pentandione residue. Treatment of the ligands H₂L with copper(II) actetate in the presence of pyridine led to the formation of copper complexes [CuL(py)]. In each of the complexes the copper atoms adopt a distorted square‐pyramidal coordination. Three of the basal coordination sites are occupied by the doubly deprotonated Schiff Bases L^2– which act as tridentate chelating O, N, O‐ligands. The remaining coordination sites are occupied by a pyridine ligand at the base and a carboxyl oxygen atom of a neighboring complex at the apical position. The latter coordination is responsible for a catenation of the complexes in the solid state.     

1, 9‐Dihydro‐purine‐6‐thione Derivatives of the d8–d10 Metal Ions (PdII,PtII, and CuI): Synthesis,Spectroscopy, and Structures

Reaction of 1, 9‐dihydro‐purine‐6‐thione (puSH₂) in presence of aqueous sodium hydroxide with PdCl₂(PPh₃)₂ suspended in ethanol formed [Pd(κ²‐N⁷,S‐puS)(PPh₃)₂] ( 1 ). Similarly, complexes [Pd(κ²‐N⁷,S‐puS)(κ²‐P, P‐L‐L)] ( 2 – 4 ) {L‐L = dppm (m = 1) ( 2 ), dppp (m = 3) ( 3 ), dppb (m = 4) ( 4 )} were prepared using precursors the [PdCl₂(L‐L)] {L‐L = Ph₂P–(CH₂)_m–PPh₂}. Reaction of puSH₂ suspended in benzene with platinic acid, H₂PtCl₆, in ethanol in the presence of triethylamine followed by the addition of PPh₃ yielded the complex [Pt(κ²‐N⁷,S‐puS)(PPh₃)₂] ( 5 ). Complexes [Pt(κ²‐N⁷,S‐puS)(κ²‐P, P‐L‐L)] ( 6 – 8 ) {L‐L = dppm ( 6 ), dppp ( 7 ), dppb ( 8 )} were prepared similarly. The 1, 9‐dihydro‐purine‐6‐thione acts as N⁷,S‐chelating dianion in compounds 1 – 8 . The reaction of copper(I) chloride [or copper(I) bromide] in acetonitrile with puSH₂ and the addition of PPh₃ in methanol yielded the same product, [Cu(κ²‐N⁷,S‐puSH)(PPh₃)₂] ( 9 ), in which the halogen atoms are removed by uninegative N, S‐chelating puSH^– anion. However, copper(I) iodide did not lose iodide and formed the tetrahedral complex, [CuI(κ¹‐S‐puSH₂)(PPh₃)₂] ( 10 ), in which the thio ligand is neutral. These complexes were characterized with the help of elemental analysis, NMR spectroscopy (¹H, ³¹P), and single‐crystal X‐ray crystallography ( 3 , 7 , 8 , 9 , and 10 ).     

Synthesis,Structure and Magnetic Properties of a Novel N‐Benzenesulfonyl‐L‐glutamic Acid‐bridged Manganese(II) Polymer with Double‐Chain Structure

First N‐benzenesulfonyl‐L‐glutamic acid‐bridged manganese(II) coordination polymer [Mn(bipy)(bs‐glu)]_n (bs‐glu = N‐benzenesulfonyl‐L‐glutamic acid dianion, bipy = 2, 2′‐bipyridine) has been synthesized and characterized structurally and magnetically. It crystallizes in the orthorhombic space group P2₁2₁2₁. The γ‐carboxyl group coordinates to the Mn^II atom in a chelating mode, while the α‐carboxyl group coordinates in a bidentate‐bridging mode. The complex displays a one‐dimensional double‐chain polymer. Magnetic measurements show that there are weak antiferromagnetic interactions between the adjacent Mn^II ions in the compound.     

Electrochemical Determination of L‐Lactate Using Phenylboronic Acid Monolayer‐Modified Electrodes

The surface of a gold (Au) disk electrode was modified with a self‐assembled monomolecular layer of dithiobis(4‐butylamino‐m‐phenylboronic acid) (DTBA‐PBA) to prepare L ‐lactate‐sensitive electrodes. The DTBA‐PBA‐modified electrodes exhibited an attenuated cyclic voltammogram (CV) for the Fe(CN)₆^3? ion in the presence of L ‐lactate, as a result of the formation of phenylboronate ester of L ‐lactate accompanied with the addition of OH^? ion to the boron atom. In other words, the negatively charged DTBA‐PBA monolayer blocked the electrode surface from the access of the Fe(CN)₆^3?/4? ions. Thus, the DTBA‐PBA monolayer‐modified Au electrode can be used for determining L ‐lactate on the basis of the change in redox current of Fe(CN)₆^3?/4? ions. The calibration graph useful for determining 1–30 mM L ‐lactate was obtained.     

Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

Target Visualization by MRI Using the Avidin/Biotin Amplification Route: Synthesis and Testing of a Biotin–Gd‐DOTA Monoamide Trimer

To design efficient targeting strategies in magnetic resonance (MR) molecular imaging applications, the formation of supramolecular adducts between (strept)avidin ((S)Av) and tribiotinylated Gd‐DOTA‐monoamide complexes (DOTA=1,4,7,10‐tetraazacyclododecane‐N,N′,N′′,N′′′‐tetraacetic acid) was explored. Two compounds based on the trivalent core of tris(2‐aminoethyl)amine each containing three biotin molecules and one ( L1 ) or three ( L2 ) DOTA‐monoamide (DOTAMA) ligands were synthesized. In these tribiotinylated derivatives the biotins are spaced far enough apart to allow the formation of the supramolecular adduct with the protein and to host the chelating units in between the (S)Av layers. Size exclusion HPLC analyses indicated complete formation of very high molecular weight polymers (>2 MDa) with (S)Av in solution. A ¹H NMR spectroscopy relaxometric study on the obtained polymeric adducts showed a marked increase of the relaxivity at 35–40 MHz as a consequence of the lengthening of the tumbling time due to the formation of Gd‐chelates/(S)Av polymers. The most efficient Gd₃ L2 /(S)Av polymeric system was used for a test in cell cultures. The target is represented by a neural cell adhesion molecule (NCAM), which is overexpressed in Kaposi’s sarcoma cells and tumor endothelial cells (TEC) and that is efficiently recognized by a biotinylated tetrameric peptide (C3d‐Bio). In vitro experiments showed that only cells incubated with both C3d‐Bio and Gd₃ L2 /SAv polymer were hyperintense with respect to the control. Relaxation rates of cell pellets incubated with Gd₃ L2 /SAv alone were not significantly different from the untreated cells demonstrating the absence of a specific binding.     

Preparation and characterization of poly(2‐methacryloyloxyethyl phosphorylcholine)‐block‐poly(D,L‐lactide) polymer nanoparticles

A poly(D,L ‐lactide)–bromine macroinitiator was synthesized for use in the preparation of a novel biocompatible polymer. This amphiphilic diblock copolymer consisted of biodegradable poly(D,L ‐lactide) and 2‐methacryloyloxyethyl phosphorylcholine and was formed by atom transfer radical polymerization. Polymeric nanoparticles were prepared by a dialysis process in a select solvent. The shape and structure of the polymeric nanoparticles were determined by ¹H NMR, atomic force microscopy, and ζ‐potential measurements. The results of cytotoxicity tests showed the good cytocompatibility of the lipid‐like diblock copolymer poly(2‐methacryloyloxyethyl phosphorylcholine)‐block‐poly(D,L ‐lactide). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 688–698, 2007     

A new phosphorescent heteroleptic cuprous complex with a neutral 2‐methylquinolin‐8‐ol ligand: synthesis,structure characterization,properties and TD–DFT calculations

Luminescent Cu^I complexes have emerged as promising substitutes for phosphorescent emitters based on Ir, Pt and Os due to their abundance and low cost. The title heteroleptic cuprous complex, [9,9‐dimethyl‐4,5‐bis(diphenylphosphanyl)‐9H‐xanthene‐κ²P ,P ](2‐methylquinolin‐8‐ol‐κ²N ,O )copper(I) hexafluorophosphate, [Cu(C₁₀H₉NO)(C₃₉H₃₂OP₂)]PF₆, conventionally abbreviated as [Cu(Xantphos)(8‐HOXQ)]PF₆, where Xantphos is the chelating diphosphine ligand 9,9‐dimethyl‐4,5‐bis(diphenylphosphanyl)‐9H‐xanthene and 8‐HOXQ is the N ,O‐chelating ligand 2‐methylquinolin‐8‐ol that remains protonated at the hydroxy O atom, is described. In this complex, the asymmetric unit consists of a hexafluorophosphate anion and a whole mononuclear cation, where the Cu^I atom is coordinated by two P atoms from the Xantphos ligand and by the N and O atoms from the 8‐HOXQ ligand, giving rise to a tetrahedral CuP₂NO coordination geometry. The electronic absorption and photoluminescence properties of this complex have been studied on as‐synthesized samples, whose purity had been determined by powder X‐ray diffraction. In the detailed TD–DFT (time‐dependent density functional theory) studies, the yellow emission appears to be derived from the inter‐ligand charge transfer and metal‐to‐ligand charge transfer (M +L ′)→LCT excited state (LCT is ligand charge transfer).     

Enhancement of TbIII–CuII Single‐Molecule Magnet Performance through Structural Modification

We report a series of 3d–4f complexes {Ln₂Cu₃(H₃L)₂X_n} (X=OAc^?, Ln=Gd, Tb or X=NO₃^?, Ln=Gd, Tb, Dy, Ho, Er) using the 2,2′‐(propane‐1,3‐diyldiimino)bis[2‐(hydroxylmethyl)propane‐1,3‐diol] (H₆L) pro‐ligand. All complexes, except that in which Ln=Gd, show slow magnetic relaxation in zero applied dc field. A remarkable improvement of the energy barrier to reorientation of the magnetisation in the {Tb₂Cu₃(H₃L)₂X_n} complexes is seen by changing the auxiliary ligands (X=OAc^? for NO₃^?). This leads to the largest reported relaxation barrier in zero applied dc field for a Tb/Cu‐based single‐molecule magnet. Ab initio CASSCF calculations performed on mononuclear Tb^III models are employed to understand the increase in energy barrier and the calculations suggest that the difference stems from a change in the Tb^III coordination environment (C_4v versus C_s).     

Variable Bonding Modes of Pyrimidine‐2‐thione in PdII/PtII Complexes [M(η2‐N,S‐pymS)(η1‐S‐pymS)(PPh3)] and [M(η1‐S‐pymS)2(L‐L)] (L‐L = dppm,dppe)

Reactions of pyrimidine‐2‐thione (HpymS) with Pd^II/Pt^IV salts in the presence of triphenyl phosphine and bis(diphenylphosphino)alkanes, Ph₂P‐(CH₂)_m‐PPh₂ (m = 1, 2) have yielded two types of complexes, viz. a) [M(η²‐N, S‐ pymS)(η¹‐S‐ pymS)(PPh₃)] (M = Pd, 1 ; Pt, 2 ), and (b) [M(η¹‐S‐pymS)₂(L‐L)] {L‐L, M = dppm (m = 1) Pd, 3 ; Pt, 4 ; dppe (m = 2), Pd, 5 ; Pt, 6 }. Complexes have been characterized by elemental analysis (C, H, N), NMR spectroscopy (¹H, ¹³C, ³¹P), and single crystal X‐ray crystallography ( 1 , 2 , 4 , and 5 ). Complexes 1 and 2 have terminal η¹‐S and chelating η²‐N, S‐modes of pymS⁻, while other Pd/Pt complexes have only terminal η¹‐S modes. The solution state ³¹P NMR spectral data reveal dynamic equilibrium for the complexes 3 , 5 and 6 , whereas the complexes 1 , 2 and 4 are static in solution state.     

Synthesis and ring‐opening (co)polymerization of L‐lysine N‐carboxyanhydrides containing labile side‐chain protective groups

This contribution describes the synthesis and ring‐opening (co)polymerization of several L ‐lysine N‐carboxyanhydrides (NCAs) that contain labile protective groups at the ?‐NH₂ position. Four of the following L ‐lysine NCAs were investigated: N^?‐trifluoroacetyl‐L ‐lysine N‐carboxyanhydride, N^?‐(tert‐butoxycarbonyl)‐L ‐lysine N‐carboxyanhydride, N^?‐(9‐fluorenylmethoxycarbonyl)‐L ‐lysine N‐carboxyanhydride, and N^?‐(6‐nitroveratryloxycarbonyl)‐L ‐lysine N‐carboxyanhydride. In contrast to the harsh conditions that are required for acidolysis of benzyl carbamate moieties, which are usually used to protect the ?‐NH₂ position of L ‐lysine during NCA polymerization, the protective groups of the L ‐lysine NCAs presented here can be removed under mildly acidic or basic conditions or by photolysis. As a consequence, these monomers may allow access to novel peptide hybrid materials that cannot be prepared from ?‐benzyloxycarbonyl‐L ‐lysine N‐carboxyanhydride (Z‐Lys NCA) because of side reactions that accompany the removal of the Z groups. By copolymerization of these L ‐lysine NCAs with labile protective groups, either with each other or with γ‐benzyl‐L ‐glutamate N‐carboxyanhydride or Z‐Lys NCA, orthogonally side‐chain‐protected copolypeptides with number‐average degrees of polymerization ≤20 were obtained. Such copolypeptides, which contain different side‐chain protective groups that can be removed independently, are interesting for the synthesis of complex polypeptide architectures or can be used as scaffolds for the preparation of synthetic antigens or protein mimetics. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1167–1187, 2003     

Unusual hydrogen bonding in L‐cysteine hydrogen fluoride

L‐Cysteine hydrogen fluoride, or bis(L‐cysteinium) difluoride–L‐cysteine–hydrogen fluoride (1/1/1), 2C₃H₈NO₂S⁺·2F⁻·C₃H₇NO₂S·HF or L‐Cys⁺(L‐Cys...L‐Cys⁺)F⁻(F⁻...H—F), provides the first example of a structure with cations of the `triglycine sulfate' type, i.e.A⁺(A...A⁺) (where A and A⁺ are the zwitterionic and cationic states of an amino acid, respectively), without a doubly charged counter‐ion. The salt crystallizes in the monoclinic system with the space group P2₁. The dimeric (L‐Cys...L‐Cys⁺) cation and the dimeric (F⁻...H—F) anion are formed via strong O—H...O or F—H...F hydrogen bonds, respectively, with very short O...O [2.4438 (19) Å] and F...F distances [2.2676 (17) Å]. The F...F distance is significantly shorter than in solid hydrogen fluoride. Additionally, there is another very short hydrogen bond, of O—H...F type, formed by a L‐cysteinium cation and a fluoride ion. The corresponding O...F distance of 2.3412 (19) Å seems to be the shortest among O—H...F and F—H...O hydrogen bonds known to date. The single‐crystal X‐ray diffraction study was complemented by IR spectroscopy. Of special interest was the spectral region of vibrations related to the above‐mentioned hydrogen bonds.