Symmetrical and unsymmetrical incorporation of active biological monomers on the surface of phosphorus dendrimers

Phosphorus-containing dendrimers are attractive carriers for the delivery of bioactive molecules due to their very particular architecture, globular shape and chemical and physical properties. Herein we report a simple synthetic approach of ethacrynic acid derivatives loaded-phosphorus dendrimers by symmetrical grafting of ethacrynic acid analogues by nucleophilic substitution of each chlorine of P(S)Cl₂ end groups. We report also for the first time an unsymmetrical grafting of two different phenol derivatives by a selective substitution of one chlorine of P(S)Cl₂ end group followed by the grafting of the second phenol.     

Multiplurifunctionalized Phosphorus Dendrimers: Selective Functionalization of P(X)CL2 Terminal Groups

Abstract

Dendrimers are hyperbranched macromolecules constituted of repetitive branched units. They are synthesized step-by-step, a method which ensures a perfectly defined structure. This mini-review reports examples of rare “multiplurifunctionalized” dendrimers that have several types of functional groups precisely located on each terminal branching point. They are obtained thanks to the specificity of the reactivity of each Cl of P(X)Cl₂ (X = generally S, but also O) terminal groups on the surface of poly(phosphorhydrazone) dendrimers.     

On the scent of Spherical Dendrimers: Cyclophosphazenic Dandelion Dendrimers Up to the Eighth Generation

Abstract

Preparation of spherical dendrimers up to the eighth generation from D_3h cyclophosphazenic hexadangling cores (coded as sexapus) involves two repetitive steps: aminolysis of hexachlorocyclotriphosphazene, N₃P₃Cl₆ 0, by long-chain aliphatic diamines (such as 1,6-Diaminohexane and higher cousins) leading to sexapus cores with dangling diamino groups followed by a grafting of N₃P₃Cl₅ flagstones as 5-fold growing multipliers on these amino endings. Dendrimers of the first (compounds 1a, b) to the eighth (compounds 8a, b) are described. Dendrimer of the eighth generation, 8b, possesses 2,343,750 terminal (P-Cl) functions (molecular weight 228,977,179).     

Synthesis and photophysical properties of poly-(phenylenevinylene) dendrimers with a ruthenium tris-bipyridine core

The photophysical processes have been investigated in first, second and third generation dendrimers with poly-(phenylenevinylene) branches and a ruthenium tris-bipyridine core, RuDn (n = 1–3). These dendrimers show very efficient forward singlet–singlet energy transfer from the branches to the ruthenium core upon UV irradiation, with efficiencies of 0.99 for RuD1 and 0.88 for RuD2 and RuD3 in CH₂Cl₂. The RuDn dendrimers show a bi-exponential emission decay in CH₂Cl₂, when excited with a 460 nm light with short lifetimes, however, the emission decay lifetimes become mono-exponential in 10% Triton X-100 aqueous solution (τ = 840 ns for RuD1, 890 ns for RuD2 and 1120 ns for RuD3).     

Tailored modification of quartz surfaces by covalent immobilization of small molecules (γ-aminopropyltriethoxysilane), monodisperse macromolecules (dendrimers), and poly(styrene/acrolein/divinylbenzene) microspheres with narrow diameter distribution

Quartz plates were modified by consecutive immobilization of γ-aminopropyltriethoxysilane (APTS), phosphorus containing dendrimers with aldehyde groups (generation 5 – G5), Starburst PAMAM dendrimers generation 4 (G4-PAMAM), and poly(styrene/acrolein/divinylbenzene) microspheres [P(SAD)]. In this way surfaces with heterogeneity on molecular, macromolecular, and microscopic levels, and which were equipped with functional amino or aldehyde groups were obtained. Surface layers were characterized by X-ray photoelectron spectroscopy (XPS) and by contact-angle measurements. Analysis of XPS spectra revealed that the thickness of the layer of G5 on the SiO₂-APTS substrate was 3.7 nm, i.e., the thickness was typical for macromolecular dimensions. The average thickness of the layer of PAMAM dendrimers on SiO₂-APTS-G5 was found to be 0.35 and 0.29 nm, depending on whether calculations were based on attenuation of the intensity of the Si2p or the P2p signal respectively. This thickness was unreasonably low for a monolayer of PAMAM dendrimers and indicated that the surface of the SiO₂-APTS-G5 substrate was incompletely covered with these macromolecules. The XPS method was also used for the determination of the degree of coverage of the surface of a SiO₂-APTS-G5-PAMAM plate with P(SAD) microspheres. The degree of coverage was found to be 0.60 and approaches the maximum theoretically possible value (0.62) for microspheres attached chaotically and irreversibly to the surface in an arrangement one microsphere thick. Subsequent coverage of the SiO₂-APTS-G5-PAMAM-P(SAD) substrate with PAMAM dendrimers resulted in the formation of a PAMAM adlayer 3.2 nm thick, close to the molecular dimensions of these dendrimers. Contact-angle measurements revealed considerable differences in the hydrophobicity of the surfaces of the quartz plates, depending on their modification. Hydrophobicity increased in the order SiO₂ < SiO₂-APTS-G5-PAMAM < SiO₂-APTS ≤ SiO₂-APTS-G5 < SiO₂-APTS-G5-PAMAM-P(SAD). Received: 17 March 1998 Accepted: 14 September 1998     

Palladocarbosilane dendrimers as catalysts for the asymmetric hydrovinylation of styrene in supercritical carbon dioxide

The palladocarbosilane dendrimers 2 and 3, containing the P-stereogenic phosphine [P(2-biphenylyl)PhCH₂] fragment, and the model compound Me₃Si(P(2-biphenylyl)PhCH₂)(PdCl(η³-2-MeC₃H₄)), 1, were tested as precatalysts in the hydrovinylation of styrene, in supercritical CO₂ medium. Na[BARF] was used as a cocatalyst. In all cases, the activity was somewhat less than that observed in CH₂Cl₂, but the selectivity and enantiomeric excess were excellent and comparable with the results obtained using the conventional solvent.     

Darstellung und Eigenschaften der Imidodiphosphorsäureamide

Preparation and Properties of Imidodiphosphoric Acid Amides Trichlorophosphazene phosphoryldichloride, Cl₃P?N? P(O)Cl₂, reacts with the stoichiometric amount of anhydrous formic acid resulting the tetrachloride of the imidodiphosphoric acid, Cl₂(O)P? NH? P(O)Cl₂. This tetrachloride yields with diazomethane the N-methyl compound, Cl₂(O)P? N(CH₃)? P(O)Cl₂. The tetramide of the imidodiphosphoric acid and its octalkyl derivatives are obtained by reaction of the tetrachloride with ammonia, dimethylamine, and diethylamine, respectively.     

Bildung und NMR-spektroskopische Charakterisierung von Alk-(ar-)oxyderivaten von Trichlorphosphazen-N-phosphoryldichlorid,Cl3PN?P(O)Cl2, Imido- und N-Methylimidodiphosphoryltetrachlord,Cl2P(O)NHP(O)Cl2 bzw. Cl2P(O)N(CH3)P(O)Cl2

Formation and N.M.R.-Spectroscopic Characterization of Alk-(ar-)oxy Derivatives of Trichlorophosphazene-N-phosphoryldichloride, Cl₃P?N? P(O)Cl₂, Imido- and N-Methylimidodiphosphoryltetrachloride, Cl₂P(O)NHP(O)Cl₂ and Cl₂P(O)N(CH₃)P(O)Cl₂ The ester chlorides and esters P₂NOCl_5?x(OR)_x (x = 1?5), P₂(NH)O₂Cl_4?x(OR)_x (x = 1–4) and P₂(NCH₃)O₂Cl_4–x(OR)_x (x = 1–4) derived from the title compounds by substitution of chlorine atoms by alk- or aroxy groups are characterized by their ³¹P-n.m.r. data. The possibilities for forming these compounds by alcoholysis, chloridolysis, dealkylation and P? N-bond formation are discussed.     

Beitrag zur Chemie der Phosphor-Stickstoff-Verbindungen. Reaktion von Cl2(O)P?NH?P(O)Cl2 mit Tetrahydrofuran

Contribution to the Chemistry of Phosphorus-Nitrogen Compounds. Reaction of Cl₂(O)P? NH? P(O)Cl₂ with Tetrahydrofuran As well as many phosphorus compounds, the imidodiphosphoryl tetrachloride HN(P(O)Cl₂)₂ reacts with a large excess of tetrahydrofuran to give the polytetrahydrofuran. Otherwise, if we use smaller molecular ratios THF/HN(P(O)Cl₂)₂ (1/2 to 3) a polytetrahydrofuran with short chains and N(ω-hydroxypolytetramethylenoxy)imidodiphosphoryl tetrachloride R? N(P(O)Cl₂)₂; R = H(O(CH₂)₄)_n- are obtained at 22° or 30°C. The ¹H and ³¹P n.m.r. spectra show that oxonium ions are formed with progressive additions of THF to HN(POCl₂)₂/CCl₄ solution. Then two mechanisms have been considered by nucleophilic attack on carbon α of oxonium ion coming from: the free electronic dublett on oxygen of THF to give polytetrahydrofuran or (and) from the nitrogen of imido diphosphoryl tetra chloride anion ((Cl₂OP)₂N)^? to obtain N(ω-hydroxypolytetramethylenoxy)imidodiphosphoryl tetrachloride.     

Synthesis of Organoplatinum Poly(dendrimer)s: Pronounced Effect of Size and Geometry of Small Organoplatinum Linkers on the Copolymerization Efficiency with Bifunctional Dendritic Macromonomers

The copolymerizations of two series of surface functionalized bis(acetylene) G1–G3 dendrimers, one ( S ‐ Gn ) having a structural rigid skeleton and the other ( L ‐ Gn ) a relatively more flexible architecture, with two platinum linkers, cis‐[(Et₂PCH₂CH₂PEt₂)PtCl₂] ( 2 ) and [Cl(Et₃P)₂Pt‐C?C‐p‐C₆H₄‐]₂ ( 3 ) were investigated. For both series of dendrimers, only linear and/or cyclic oligomers were formed when the cis‐platinum linker 2 was used. However, high molecular weight (100–200 kD) organoplatinum poly(dendrimer)s were obtained from both series when the elongated linear rod‐liked platinum linker 3 was employed and the formation of cyclic oligomers was greatly suppressed for both the structural rigid S ‐ Gn and the structural flexible L ‐ Gn series. These results are in sharp contrast to our earlier findings (S.‐Y. Cheung, H.‐F. Chow, T. Ngai, X. Wei, Chem. Eur. J. 2009 , 15, 2278–2288) obtained by using a shorter linear platinum linker trans‐[Pt(PEt₃)₂Cl₂] ( 1 ), where a larger amount of cyclic oligomers was formed from the structural flexible L ‐ Gn dendrimers. A model was proposed to rationalize how the geometry and size of the platinum linker could control the copolymerization behaviours of these dendritic macromonomers.     

Synthesis and catalytic activities of Pd-phosphine complexes modified poly(ether imine) dendrimers

In this paper, we report synthesis of new alkyldiphenyl phosphine ligand modified poly(ether imine) dendrimers up to the third generation. The phosphinated dendrimers were obtained by functional group transformations of the alcohols present at the periphery of the dendrimers to chloride, followed by phosphination using LiPPh₂. The modification at the peripheries of the dendrimers was performed successfully to obtain up to 16 alkyl diphenylphosphines in the case of a third generation dendrimer, in good yields for each individual step. After phosphination, dendritic ligands were complexed with Pd(COD)Cl₂ to give dendritic phosphine-Pd^II complexes. Both the ligands and the metal complexes were characterized by spectroscopic and spectrometric techniques including high-resolution mass spectral analysis for the lower generations. Evaluation of the catalytic efficacies of the dendrimer-Pd^II metal complexes in mediating a prototypical C-C bond forming reaction, namely the Heck reaction, was performed using various olefin substrates. While the substrate conversion lowered with catalyst in the order from monomer to third generation dendrimer, the second and third generation dendrimers themselves were found to exhibit significantly better catalytic activities than the monomer and the first generation dendrimer.     

Zweikernige Palladium(II)‐, Platin(II)‐ und Iridium(III)‐Komplexe von Bis[imidazol‐4‐yl]alkanen

Dinuclear Palladium(II), Platinum(II), and Iridium(III) Complexes of Bis[imidazol‐4‐yl]alkanes The reaction of bis(1,1′‐triphenylmethyl‐imidazol‐4‐yl) alkanes ((CH₂)_n bridged imidazoles L(CH₂)_nL, n = 3–6) with chloro bridged complexes [R₃P(Cl)M(μ‐Cl)M(Cl)PR₃] (M = Pd, Pt; R = Et, Pr, Bu) affords the dinuclear compounds [Cl₂(R₃P)M–L(CH₂)_nL–M(PR₃)Cl₂] 1 – 17 . The structures of [Cl₂(Et₃P)Pd–L(CH₂)₃L–Pd(PEt₃)Cl₂] ( 1 ), [Cl₂(Bu₃P)Pd–L(CH₂)₄L–Pd(PBu₃)Cl₂] ( 10 ), [Cl₂(Et₃P)Pd–L(CH₂)₅L–Pd(PEt₃)Cl₂] ( 3 ), [Cl₂(Et₃P)Pt–L(CH₂)₃L–Pt(PEt₃)Cl₂] ( 13 ) with trans Cl–M–Cl groups were determined by X‐ray diffraction. Similarly the complexes [Cl₂(Cp*)Ir–L(CH₂)_nL–Ir(Cp*)Cl₂] (n = 4–6) are obtained from [Cp*(Cl)Ir(μ‐Cl)₂Ir(Cl)Cp*] and the methylene bridged bis(imidazoles).     

Beitrag zur Chemie der Phosphor-Stickstoff-Verbindungen Reaktion von Cl3PN?P(O)Cl2 mit Tetrahydrofuran

Contribution to the Chemistry of Phosphorus Nitrogen Compounds. Reaction of Cl₃P?N? P(O)Cl₂ with Tetrahydrofuran As well as many phosphorus compounds, the trichlorophosphazene phosphoryldichloride Cl₃P?N? P(O)Cl₂ reacts at 30°C with a large excess of tetrahydrofuran to give the polytetrahydrofuran. Otherwise, if we use higher molecular ratios Cl₃P?N? P(O)Cl₂/THF (respectively 1/3 and 1) we obtain at 30°C beside polytetrahydrofuran the N chlorobutylimidodiphosphoryltetrachloride. This last compound is the main one obtained at 60°C and is probably formed by rearrangement of the O chlorobutyl isomer. However the formation of small quantities of polytetrahydrofuran chains linked with phosphorus cannot be avoided.     

Improved Synthesis of the [Ru(η6‐p‐cymene)Cl3] Anion: Facile Isolation under Mild Conditions

Reaction of [Ru(η⁶‐p‐cymene)Cl₂]₂ with two equivalents of [Ph₄P][Cl] in CH₂Cl₂ yields [Ph₄P][Ru(η⁶‐p‐cymene)Cl₃], containing a trichlororuthenate(II) anion. In solution, an equilibrium between the product and [Ru(η⁶‐p‐cymene)Cl₂]₂ is observed, which in CDCl₃ is nearly completely shifted to the dimer, whereas in CD₂Cl₂ essentially a 1:1‐mixture of the two ruthenium species is present. Crystallization from CH₂Cl₂/pentane yielded two different crystals, which were identified by X‐ray analysis as [Ph₄P][Ru(η⁶‐p‐cymene)Cl₃] and [Ph₄P][Ru(η⁶‐p‐cymene)Cl₃]·CH₂Cl₂.     

芳醚树枝形聚合物的合成及分子内光敏异构化反应研究

利用收敛法合成了一代到四代外围带有二苯酮、核心带有降冰片二烯的芳醚树枝形聚合物, 初步研究了这些化合物的分子内光敏异构化反应. 以波长大于350 nm的光选择激发外围的二苯酮官能团引起核心处降冰片二烯基团异构化为四环烷, 随着代数的增长, 光敏异构化反应的速率逐渐加快.     

Preparation and properties of perfluorochloromethyl-mercaptophosphoryldichlorides and -chlorophosphanes

In Arbuzov-type reactions CF_nCl_3?nSCl reacts with ROPCl₂ (R = CH₃, C₂H₅) to give CF_nCl_3?nSP(O)Cl₂ (n = 3,2,1,0). The corresponding reaction with CF₃SeX (X = Cl, Br) produces CF₃SeP(O)Cl₂ in good yields only in the presence of catalysts such as SbCl₅ or BCl₃. Reactions between P₄ and the sulfenylchlorides produce (CF_nCl_3?nS)_xPCl_3?n (n = 3,2,1 and x = 1,2). On heating CF_n′ Cl_3?n′ SP(O)Cl₂ (n′ = 2,1,0) decompose to P(O)Cl₃ and SCF_n′ Cl_2?n′. During this process fluorination of P(O)Cl₃ to P(O)F₃ by SCF₂ is observed. A Cl/Br exchange between CF_nCl_3?nSP(O)Cl₂ (n = 3,2) and PBr₃ was proved ¹⁹F? and ³¹P-NMR-spectroscopically.Chemical and physical properties of the newly synthesized compounds will be discussed.     

Die Kristallstrukturen von (Ph4P)2[HfCl6]·2CH2Cl2 und (Ph4P)2[Hf2Cl10]·CH2Cl2

Crystal Structures of (Ph₄P)₂[HfCl₆]·2CH₂Cl₂ and (Ph₄P)₂[Hf₂Cl₁₀]·CH₂Cl₂ Colourless single crystals of (Ph₄P)₂[HfCl₆]·2CH₂Cl₂ ( 1 ) and (Ph₄P)₂[Hf₂Cl₁₀]·CH₂Cl₂ ( 2 ) were obtained from hafniumtetrachloride and tetraphenylphosphonium chloride in dichloromethane solution, using the corresponding stoichiometry of the educts. Both compounds were characterized by X‐ray structure determinations. 1 : Space group P1¯, Z = 1, lattice dimensions at 193 K: a = 1018.3(1), b = 1121.0(1), c = 1240.1(1) pm, α = 70.55(1)°, β = 81.38(1)°, γ = 80.02(1)°, R₁ = 0.0374. 2 : Space group P1¯, Z = 1, lattice dimensions at 193 K: a = 1124.4(1), b = 1141.9(1), c = 1281.4(1) pm, α = 63.80(1)°, β = 68.15(1)°, γ = 86.33(1)°, R₁ = 0.0208.     

Cyclam‐Cored Dendrimers Appended with Four Dendrons of Two Different Types: Intradendrimer Energy Transfer

We have synthesized two cyclam‐cored dendrimers appended with dendrons of two different types by proper protection/deprotection of the cyclam unit. The resulting dendrimers contain six naphthyl and two dansyl units ( N6 D2 ) or two dansyl and six naphthyl units ( N2 D6 ) at the periphery. Their photophysical properties have been compared to those of a dendrimer containing 8 dansyl units ( D8 ) and a previously investigated dendrimer containing 8 naphthyl units ( N8 ). The absorption spectra are those expected on the basis of the number of chromophores, demonstrating that no ground state interaction takes place. The emission spectra of N2 D6 and N6 D2 show naphthalene localized and naphthalene excimer emission similar to those observed in the case of N8 , together with a much stronger dansyl emission with maximum at 525 nm. Addition of CF₃SO₃H to dendrimer solutions in CH₃CN/CH₂Cl₂ 1:1 (v/v) leads to protonation of the aliphatic amine units of the cyclam core at first and then of the aromatic amine of each dansyl chromophores. Cyclam can be diprotonated and this affects dansyl absorption and, most significantly, emission bands by a charge perturbation effect. Each dansyl unit is independently protonated in both dendrimers. The most interesting photophysical feature of these heterofunctionalized cyclam‐cored dendrimers is the occurrence of an intradendrimer photoinduced energy transfer from naphthyl to dansyl chromophores of two different dendrons (interdendron mechanism). The efficiency of this process is 50 % for N6 D2 and it can be increased up to 75 % upon protonation of the cyclam core and formation of N6 D2 (2H⁺). This arises from the fact that protonation of the amine units of the cyclam prevents formation of exciplexes upon naphthyl excitation, thus shutting down one of the deactivation processes of the fluorescent naphthyl excited state.     

Organische Phosphorverbindungen 39. Methoden zur Herstellung von Chloräthylphosphonsäuredichlorid,ClCH2CH2P(O)Cl2 und CH3CHClP(O)Cl2 [1]

It is shown that the KINNEAR -PERREN reaction with ClCH₂CH₂Cl, PCl₃, and AlCl₃ produces the two possible isomers ClCH₂CH₂P(O)Cl₂ and CH₃CHClP(O)Cl₂. Methods for the preparation of pure ClCH₂CH₂P(O)Cl₂ and pure CH₃CHClP(O)Cl₂ are described. The physical properties of a number of chloroethyl groups containing phosphorus compounds are listed.     

Synthese von Nitrenkomplexen mit N-Trimethylsilylanilin. II. Charakterisierung und Kristallstruktur der Rhenium(V)-phenylnitren-Komplexe mer-[Re(NPh)Cl3(NH2Ph)(Ph3P)] und trans-[Re(NPh)(OMe)Cl2(Ph3P)2]

Synthesis of Phenylnitrene Complexes with N-Trimethylsilylaniline. II. Characterization and Crystal Structure of the Rhenium(V) Complexes mer-[Re(NPh)Cl₃(NH₂Ph)(Ph₃P)] and trans-[Re(NPh)(OMe)Cl₂(Ph₃P)₂] Reaction of [ReOCl₃(Ph₃P)₂] with N-trimethylsilylaniline yields mer-[Re(NPh)Cl₃(Ph₃P)₂], which reacts under air with excess of N-trimethylsilylaniline to form [Re(NPh)Cl₃ · (NH₂Ph)(Ph₃P)]. Crystallization from CH₂Cl₂/MeOH affords [Re(NPh)(OMe)Cl₂(Ph₃P)₂] as an additional product. [Re(NPh)Cl₃(NH₂Ph)(Ph₃P)] crystallizes in the monoclinic space group P2₁/n with a = 1 192.3(3); b = 1 918.9(3); c = 1 266.3(3) pm; β = 101.71(1)°; Z = 4. The rhenium atom has a distorted octahedral environment with the Cl atoms in meridional positions. The phenyl nitrene ligand is coordinated with an almost linear arrangement Re? N1? C40 = 166.8(6)° and with a bond distance Re?N = 170.5(6) pm. [Re(NPh)(OMe)Cl₂(Ph₃P)₂] · 1/2CH₂Cl₂ crystallizes in the triclinic space group P1 : a = 1 103.1(4); b = 1 227.9(4); c = 1 711.3(5) pm; α = 70.48(3)°; β = 72.71(3)°; γ = 80.03(3)°; Z = 2. The rhenium atom exhibits a distorted octahedral coordination with the Cl atoms and the phosphine ligands in trans positions. As a consequence of the competition of the nitrene ligand and the trans-coordinated methoxy group the Re?;N bond length is slightly lengthened to 173.2(7) pm, while the Re? O bond length of 193.4(6) pm is short. The bond angles Re? N? C70 and Re? O? C80 are 173.3(7)° and 139.1(7)°, respectively.