Polar and hydrophobic effects on ester aminolysis in dimethyl sulfoxide

Aminolysis of various carboxyl-containing esters by several tetra-, tri-, and diamines was kinetically studied in dimethyl sulfoxide. Rates were measured in the presence or absence of added sulfuric acid with the amine concentration being much greater than the ester concentration. In some reactions, pseudo-first-order rate constants manifested saturation kinetic behavior with respect to the total amine concentration, indicating the formation of complexes between the amines and the esters. The complex formation was most efficient when the carboxyl group of the ester substrate was located at the meta position to the ester group. In addition, the complex formation was facilitated by hydrophobic amines. In order to explain the positional stereoselectivity and the hydrophobic effects observed in the kinetic study, a structure of the complex is proposed. In this structure of the complex, two nitrogen atoms of the amine are linked by an intramolecular hydrogen bond and then further interact with the two carbonyl oxygen atoms of the substrate. In addition, the hydrophobic interaction between the hydrophobic portion of the amine and the benzene ring of the substrate stabilizes the complex. Dimethyl sulfoxide accommodates both the polar and the hydrophobic interactions that are needed in the formation of the complex, mimicking the microenvironment of enzyme active sites.     

The preparation of 6-deoxy-3-O-methyl-6-nitro-D-altrose

The title compound(9) a new nitro sugar and potential starting-point for the synthesis of hitherto unknown stereoisomers in the deoxynitroinositol series, was prepared by a sequence of high-yielding reactions. Methyl 2.3-anhydro-4.6-O- benzylidene-α-D-mannopyranoside was converted into methyl 3-O-methyl-α-D-altropyranoside(3) by the action of sodium methoxide followed by debenzylidenation esssentially according to established procedures. Acetolysis of3 and subsequent Zemple´n transesterification gave syrupy 3-O-methyl-D-altrose, from which the furanoid 1,2:5.6-di-O-isopropylidene and 1,2-O-isopropylidene(7) derivatives were prepared by standard acetonation and partial Hydrolysis Periodate oxidation of 7, and addition of nitromethane to the product. furnished crystalline 6-deoxy-1.2-O-isopropylidene-3-O-methyl-6-nitro-β-D-altrofuranose(8) as the chief epimer. Deacetonation of8 by trifluoroacetic acid9 in crystalline form.     

Synthesis of monoamine derivatives of [Ir4(CO)12]. X-ray crystal structure of [Ir4(CO)11(4-picoline)]

The mono-substituted amine derivatives [Ir₄(CO)₁₁L] (L = pyridine (1), 4-methylpyridine (2), 4-ter-butyl pyridine (3), 3,5-dimethylpyridine (4), 3,4-dimethylpyridine (5)) were obtained by the reaction of [Ir₄(CO)₁₁Br]⁻ with the corresponding aromatic amine. In the solid state, cluster 2 has an approximate C_s symmetry with all terminal ligands as shown by an X-ray analysis. In solution, this unbridged structure is in dynamic equilibrium with two other isomeric forms having three edge-bridging CO’s on a common basal face and the amine ligand coordinated in axial or in radial position relative to this face.     

4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: Design,synthesis and structure–activity relationships

Single enantiomer [(aryloxy)(pyridinyl)methyl]piperidine and pyrrolidine derivatives 5–9 are inhibitors of monoamine reuptake. Structure–activity relationships established that monoamine reuptake inhibition are functions of amine, pyridine isomer, aryloxy ring substitution and stereochemistry. Consequently, selective NRIs, selective SRIs, dual SNRIs and triple SNDRIs were all identified. Dual SNRIs 5l–a and 9c were evaluated in additional pharmacology and pharmacokinetic studies as representative examples from this series.     

Reaction of methanesulphonyl chloride-N,N-dimethylformamide with partially esterified derivatives of sucrose

Treatment of sucrose 2,3,3′,4′,6-penta-acetate (1) with methanesulphonyl chloride-N,N-dimethylformamide (reagent A) gave the 1′,4,6′-trichloride 2, the 1′-O-formyl-4,6′-dichloride 3, the 4,6′-dichloride 4, and the 1′,4-di-O-formyl-6′-chloride 5. De-esterification of 3 afforded the unsubstituted 4,6′-dichloride 6 which, on acetylation, gave the corresponding hexa-acetate 7, also prepared by acetylation of 4. In compounds 2, 3, and 4, substitution at C-4 by chloride ion occurred with inversion of configuration. The structure of 5 was confirmed by conversion into the known 6′chloro-6′-deoxysucrose hepta-acetate by de-esterification followed by acetylation. Treatment of sucrose 1′,2,3,3′,4′,6′-hexa-acetate (10) with the reagent gave the 4,6-dichloride 11 and 4-O-formyl-6-chloride 12. The formyl group in 12 was selectively removed by using an anion-exchange resin to give 16. De-esterification of 12 with methanolic sodium methoxide gave 6-chloro-6-deoxysucrose (13) which, on acetylation and benzoylation, afforded the hepta-acetate 14 and the hepta-benzoate 15, respectively. Alternatively, 15 was prepared by the reaction of 1′,2,3,3′,4,4′,6′-hepta-O-benzoylsucrose with reagent A. Treatment of 14 with sodium methoxide in methanol followed by acetylation gave 3,6-anhydrosucrose hexa-acetate (24). Reaction of sucrose 2,3,3′,4,4′-pentabenzoate (17) with reagent A gave the known 1′,6,6′-trichloro-1′,6,6′-trideoxysucrose pentabenzoate (18) and 1′-O-formyl-6,6′-dichloride 19. Treatment of 19 with anion-exchange resins selectively removed the formyl group to give 20. The structure of 20 was confirmed by conversion into the 1′-chlorosulphate-6,6′-dichloride (21). Treatment of sucrose 1′,2,3,3′,4,4′-hexabenzoate (22) with reagent A gave the expected 6,6′-dichloride (23).     

Metal-ion-catalyzed hydrolysis of monomethyl and dimethyl esters of 3-(2-imidazoleazo)phthalic acid: Bifunctional catalysis by carboxyl group and the metal ion in the hydrolysis of an alkyl ester

The Cu(II) or Ni(II) ion-catalyzed hydrolysis of methyl 2-carboxy-6-(2-imidazoleazo)benzoate (1) and the corresponding dimethyl ester (2) was studied kinetically at various pH values. For 2, the ester group located at the o position to the azo substiuent was hydrolyzed. From the rate data obtained at various metal concentrations, the values of k_cat and K_f were estimated at each pH value. For the Ni(II)-catalyzed hydrolysis of 1 at pH < 4, k_cat increases as pH is lowered, indicating bifunctional catalysis by the carboxyl group and the metal ion. For most of the reactions investigated under other conditions, the ester hydrolysis was subjected to sole catalysis by the metal ions. Detailed analysis of kinetic data obtained for these reactions indicated that the metal-ion catalysis involves the rate-determining breakdown of the tetrahedral intermediates formed by the addition of a water molecule or hydroxide ion. The bifunctional catalysis by the carboxyl group and Ni(II) ion can be considered as a model for carboxypeptidase A. The kinetic data indicate that the bifunctional catalysis proceeds through the nucleophilic attack of the carboxylate ion at the Ni(II)-coordinated carbonyl group.     

Mo- and W-N2 and -CO complexes with novel mixed P/N ligands: Structural properties and implications to synthetic nitrogen fixation

Four new ligands containing a pyridine or thiazole group and one or more N-(diphenylphosphinomethyl)amine functions have been prepared and employed for the synthesis of Mo(0) and W(0) carbonyl and dinitrogen complexes. For comparison coordination of the literature-known ligand N,N-bis(diphenylphosphinomethyl)-methylamine (PNP, 1) to such systems has been investigated as well. Two new ligands are N,N-bis(diphenylphosphinomethyl)-2-aminopyridine (pyNP₂, 2) and N,N′-bis(diphenylphosphinomethyl)-2,6-diaminopyridine (PpyP, 3). In a third new ligand, N-diphenylphosphinomethyl-2-aminothiazole (thiazNP, 4), the pyridine group is replaced by thiazol. Finally, the pentadentate ligand N,N,N′,N′-tetrakis(diphenylphosphinomethyl)-2,6-diaminopyridine (pyN₂P₄, 5) has been synthesized. Coordination of ligands 2, 3 and 4 to low-valent metal centers is investigated on the basis of the three molybdenum carbonyl complexes [Mo(CO)₃(NCCH₃)(pyNP₂)] (6), [Mo(CO)₄(PpyP)] (7) and [Mo(CO)₄(thiazNP)] (8), respectively, all of which are structurally characterized. Moreover, employing ligands 1 and 2 the two dinitrogen complexes [W(N₂)₂(dppe)(PNP)] (9) and [Mo(N₂)₂(dppe)(pyNP₂) (10), respectively, are prepared. Both systems are investigated by vibrational and NMR spectroscopy; in addition, complex 10 is structurally characterized.     

Quantitative correlations relating the interaction of Zn(II)-tetraphenylporphine and horseradish peroxidase with amines

Reactions of nucleophilic substitution and enzymatic processes involving metalloporphirins (MP) are considered in terms of coordination of zinc(II)tetraphenylporphine (Zn-TPhP) with corresponding ligands/nucleophiles/substrates/bases. Linear correlations are performed between kinetic parameters of the Zn-TPhP coordination processes in chloroform (stability constants) and reactions of nucleophilic substitution both in aqueous and organic solvents involving pyridines, pyridine N-oxides, anilines, primary amines, as well as in reactions of oxidation of anilines with horseradish peroxidase in aqueous media (rate constants). Thermodynamic parameters of the complex formation and nucleophilic substitution linearly correlate with each other in the case of pyridines, anilines, and primary amines.     

Copper phosphates and phosphinates with pyridine/pyrazole alcohol co-ligands: Synthesis and structure

Copper phosphates, [Cu(dtbp)₂(pzet)₂]·H₂O (1) and [Cu(dtbp)₂(pyme)₂] (2), as well as copper phosphinate, [Cu(dppi)₂(pyet)₂] (3) have been synthesized by the reaction of copper acetate with di-tert-butyl phosphate (dtbp) or diphenyl phosphinate (dppi) in the presence of pyridine base having hydroxyl group, namely, 3,5-dimethylpyrazole-2-ethanol (pzet) or 2-(hydroxymethyl)pyridine (pyme) or 2-(2-hydroxyethyl)pyridine (pyet). Single crystal X-ray diffraction studies reveal that copper ion in all the three complexes is bonded to two phosphoryl ions (P(O)O⁻) and two pyridine co-ligands. The crystal structure of 1 reveals that the hydroxyl group of the CH₂CH₂OH moiety of pzet ligand exhibits a positional disorder between the non-bonding position and the bonding position with respect to the central copper ion along the Jahn-Teller axis. Hence, the structure of 1 can be considered to exhibit both ‘square-planar’ and ‘octahedral’ coordination geometries simultaneously for the copper ion in the same complex. A similar situation for the -OH groups has not been observed in the complexes 2 and 3 and hence the coordination geometry around the copper ion is axially elongated octahedron.     

Synthesis of derivatives of methyl β-sophoroside

Selective tritylation of methyl β-sophoroside (1) and subsequent acetylation gave the 3,4,2′,3′,4′-penta-O-acetyl-6,6′-di-O-trityl derivative, which was O-detritylated, and the product p-toluenesulfonylated, to give methyl 3,4,2′,3′,4′-penta-O-acetyl-6,6′-di-O-p-tolylsulfonyl-β-sophoroside (4) in 63% net yield. Compound 4 was also obtained in 69% yield by p-toluenesulfonylation of 1, followed by acetylation. Several, 6,6′-disubstituted derivatives of 1 were synthesized by displacement reactions of 4 with various nucleophiles. Treatment of 4 with sodium methoxide afforded methyl 3,6:3′,6′-dianhydro-β-sophoroside. Several 6- and 6′-monosubstituted derivatives of 1 were prepared, starting from the 4,6-O-benzylidene derivative of 1.     

Ribozyme-catalyzed and nonenzymatic reactions of phosphate diesters: rate effects upon substitution of sulfur for a nonbridging phosphoryl oxygen atom

The L-21 ScaI ribozyme derived from the intervening sequence of Tetrahymena thermophila pre-rRNA catalyzes a guanosine-dependent endonuclease reaction that is analogous to the first step in self-splicing of this intervening sequence. We now describe pre-steady-state kinetic experiments, with sulfur substituting for the pro-RP (nonbridging) phosphoryl oxygen atom at the site of cleavage, that test aspects of a kinetic model proposed for the ribozyme reaction (Herschlag, D., & Cech, T. R. (1990) Biochemistry 29, 10159-10171). Thio substitution does not affect the reaction with subsaturating oligonucleotide substrate and saturating guanosine ((kcat/Km)S), consistent with the previous finding that binding of the oligonucleotide substrate limits this rate constant. In contrast, there is a significant decrease in the rate of single-turnover reactions of ribozyme-bound (i.e., saturating) oligonucleotide substrate upon thio substitution, with decreases of 2.3-fold for the reaction with guanosine ((kcat/Km)G) and 7-fold for hydrolysis [i.e., with solvent replacing guanosine; kc(-G)]. These "thio effects" are consistent with rate-limiting chemistry, as shown by comparison with model reactions. Nonenzymatic nucleophilic substitution reactions of the phosphate diester, methyl 2,4-dinitrophenyl phosphate monoanion, are slowed 4-11-fold by thio substitution for reactions with hydroxide ion, formate ion, fluoride ion, pyridine, and nicotinamide. In addition, we have confirmed that thio substitution has no effect on the nonenzymatic alkaline cleavage of RNA (Burgers, P. M. J., & Eckstein, F. (1979) Biochemistry 18, 592-596). Considering the strong preference of Mg2+ for binding to oxygen rather than sulfur, the modest thio effect on the chemical step of the ribozyme-catalyzed reaction and the absence of a thio effect on the equilibrium constant for binding of the oligonucleotide substrate suggest that the pro-RP oxygen atom is not coordinated to Mg2+ in the E.S complex or in the transition state. General implications of thio effects in enzymatic reactions of phosphate diesters are discussed.     

Branched-chain sucroses: Synthesis and Wittig reaction of the 1′-aldehydo derivative of sucrose

The reaction of 2,3,4,3′,4′-penta-O-acetylsucrose (1) with 3.3 mol. equiv. of tert-butyldiphenylsilyl chloride in pyridine in the presence of 4-dimethylamino-pyridine gave the 6,1′,6′-tris(tert-butyldiphenylsilyl) derivative 2 (27%) and the 6,6′-bis(tert-butyldiphenylsilyl) derivative (67%). Oxidation of the HO-1′ in 3 with methyl sulphoxide and trifluoroacetic anhydride gave the 1′-aldehydo derivative 5, which reacted with the stabilised Wittig reagent (Ph₃PCHCO₂Et) to give the 1′-ethoxycarbonylmethylene derivative 6. Deacetylation of the hepta-acetate 7 of 6 with methanolic sodium methoxide was accompanied by a Michael addition reaction to give 2,1′-anhydro-1′-methoxycarbonylmethylsucrose.     

Donor atom preferences in substitution reactions of trans-platinum mononucleobase compounds: Implications for DNA–protein selectivity

The competitive reactions of mononucleobase cations SP-4-2-[PtCl(9-EtGua)(NH₃)(quinoline)]⁺, 1, and trans-[PtCl(9-EtGua)(pyridine)₂]⁺, 2, with 5′-guanosine monophosphate (5′-GMP) and N-Acetylmethionine (N-AcMet) were studied by ¹H NMR Spectroscopy. The results confirmed the previously observed kinetic selectivity for sulfur over nitrogen binding. The symmetric bis(pyridine) complex reacted faster than the ammine/quinoline moiety – the estimated half-times for reaction with 5′-GMP and N-AcMet were, respectively, 7.4 and 2.3 h for 1 and 4.90 and <0.75 h for 2. Thus modification of the planar amine can enhance sulfur selectivity – based on the observed rates a S/N selectivity ratio of 3.2 is obtained for 1 but >6.5 for 2. Applications of these findings were extended to study the reaction of 1 and 2 with Ubiquitin. One principal adduct corresponding to chloride displacement is observed for both species and in this case little difference in rate is observed. The likely binding site is the unique methionine residue. The percentage of platinum-bound ubiquitin is higher for 1 and 2 than the parent dichlorides trans-[PtCl₂(NH₃)(quinoline)] and trans-[PtCl₂(pyridine)₂]. The results suggest that systematic ligand modification can modulate sulfur donor specificity and suggest possible structural features for design of platinum-based bifunctional DNA–protein cross-linking agents, rather than the DNA–DNA cross-linking principally adopted by the anticancer drug cisplatin and congeners.     

Synthesis of novel polyethyleneimine derivatives by stepwise, reversible blocking of primary and secondary amines

In the design of polyethyleneimine derivatives for use as catalysts and binding media, the placement of reactive and hydrophobic groups previously has been limited by the specificity of the addition reaction. In this paper is described a protocol to limit the sites of addition of nucleophiles and long-chain alkanes to tertiary amines and the less reactive of the secondary amines. Three blocking groups for the primary and secondary amines were tested, but only trifluoroacteylating reagents left the polymer reactive to substitution on the tertiary amines with halogenated alkanes. The secondary amines that resisted trifluoroacetylation were blocked with either tert-butyloxy carbonate or trimethylsilyl carbonate. The tertiary amines were quaternized with iodododecane or dodecyl benzyl chloride. After removal of the trifluoroacetyl groups, the polymer amines were inactivated by methylation, which proceeded to 93% completion. The 7% of the amines that were not quaternized were largely tertiary, since propylene sulfide, which reacts only with secondary and primary amines, was substituted onto the polymer only to the extent of 0.2% total amine, as quantified by the indirect method of P. H. Butterworth, F. Baum, and J. W. Porter (1967, Arch. Biochem. Biophys., 118, 716–723). The sulfhydryl group did not oxidize over at least 14 days. This is the first stable sulfhydryl-containing synthetic polymer that has been reported.     

Synthesis and some reactivity of amidinato(pyridine) complexes of molybdenum and tungsten formulated as [M(η-allyl)(amidinato)(CO)2(NC5H5)]

Bis(pyridine) complexes of molybdenum and tungsten, [M(η³-allyl)Cl(CO)₂(NC₅H₅)₂] (M=Mo; 3-Mo, M=W; 3-W), reacted with an equimolar amount of lithiated amidinate, Li[(PhN)₂CR] (R=H; 4a-Li, R = CH₃; 4b-Li), to yield corresponding amidinato(pyridine) complexes, [M(η³-allyl){(PhN)₂CR}(CO)₂(NC₅H₅)] (M=Mo, R=H; 5a-Mo, M=Mo, R=CH₃; 5b-Mo, M=W, R=H; 5a-W), as a yellow solid. The dissociation of pyridine ligand from the central metal in complexes 5a was observed in a polar solvent such as acetonitrile. In these cases, although the formation of amidinato(acetonitrile) complexes, [M(η³-allyl){(PhN)₂CH}(CO)₂(NCMe)] (M=Mo; 6a-Mo, M=W; 6a-W), was suggested spectroscopically, isolation of complexes 6a was not successful but the re-formation of pyridine complexes 5a was observed. In the reactions of complexes 5a with PEt₃ and with P(OMe)₃, the substitution reactions easily took place to give [M(η³-allyl){(PhN)₂CH}(CO)₂(PEt₃)] (M=Mo; 7a-Mo, M=W; 7a-W) and [M(η³-allyl){(PhN)₂CH}(CO)₂{P(OMe)₃}] (M=Mo; 8a-Mo, M=W; 8a-W), respectively. These complexes were characterized spectroscopically as well as, in some cases, by X-ray analyses.     

(Pyrazolylmethyl)pyridine platinum(II) and gold(III) complexes: Synthesis, structures and evaluation as anticancer agents

Reactions of 2-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (L1), 2-(3,5-diphenylpyrazol-1-ylmethyl)pyridine (L2), 2-(3,5-di-tert-butylpyrazol-1-ylmethyl)pyridine (L3) and 2-(3-p-tolylpyrazol-1-ylmethyl)pyridine (L4) with K₂[PtCl₄] in a mixture of ethanol and water formed the dichloro platinum complexes [PtCl₂(L1)] (1), [PtCl₂(L2)] (2), [PtCl₂(L3)] (3) and [PtCl₂(L4)] (4). Complex 1, [PtCl₂(L1)], could also be prepared in a mixture of acetone and water. Performing the reactions of L2 and L3 in a mixture of acetone and water, however, led to C-H activation of acetone under mild conditions to form the neutral acetonyl complexes [Pt(CH₂COCH₃)Cl(L2)] (2a) and [Pt(CH₂COCH₃)Cl(L3)] (3a). The same ligands reacted with HAuCl₄ · 4H₂O in a mixture of ethanol and water to form the gold salts [AuCl₂(L1)][AuCl₄] (5) [AuCl₂(L2)][Cl] (6) [AuCl₂(L3)][Cl] (7) and [AuCl₂(L4)][AuCl₄] (8); however, with the pyrazolyl unit in the para position of the pyridinyl ring in 4-(3,5-dimethylpyrazol-1-ylmethyl)pyridine (L5), 4-(3,5-diphenylpyrazol-1-ylmethyl)pyridine (L6) neutral gold complexes [AuCl₃(L5)] (9) and [AuCl₂(L6)] (10) were formed; signifying the role the position of the pyrazolyl group plays in product formation in the gold reactions. X-ray crystallographic structural determination of L6, 2, 33a, 8 and 10 were very important in confirming the structures of these compounds; particularly for 3a and 8 where the presence of the acetonyl group confirmed C-H activation and for 8 where the counter ion is . Cytotoxicity studies of L2, L4 and complexes 1-10 against HeLa cells showed the Au complexes were much less active than the Pt complexes.     

Combining the tail and the ring approaches for obtaining potent and isoform-selective carbonic anhydrase inhibitors: Solution and X-ray crystallographic studies

5-(3-Tosylureido)pyridine-2-sulfonamide and 4-tosylureido-benzenesulfonamide (ts-SA) only differ by the substitution of a CH by a nitrogen atom, but they have very different inhibitory properties against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). By means of X-ray crystallography on the human CA II adducts of the two compounds these differences have been rationalized. As all sulfonamides, the two compounds bind in deprotonated form to the Zn(II) ion from the enzyme active site and their organic scaffolds extend throughout the cavity, participating in many interactions with amino acid residues and water molecules. However the pyridine derivative undergoes a tilt of the heterocyclic ring compared to the benzene analog, which leads to a very different orientation of the two scaffolds when bound to the enzyme. This tilt also leads to a clash between a carbon atom from the pyridine ring of the first inhibitor and the OH moiety of Thr200, leading to less effective inhibitory properties of the pyridine versus the benzene sulfonamide derivative. Indeed, ts-SA is a promiscuous, low nanomolar inhibitor of 7 out of 10 human (h) CA isoforms, whereas the pyridine sulfonamide is a low nanomolar inhibitor only of the tumor-associated hCA IX and XII, being less effective against other 9 isoforms. Thus, a difference of one atom (N vs CH) in two isostructural sulfonamides leads to drastic differences of activity, phenomenon understood at the atomic level through the high resolution crystallographic structure and kinetic measurements reported in the paper. Combining the tail and the ring approaches in the same chemotype leads to isoform-selective, highly effective sulfonamide CA inhibitors.     

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema

Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema.In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC₅₀ of 230 nM; rat IC₅₀ of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats.     

Enhanced hydrolysis of a phosphonate ester by mono-aquo metal cation complexes

The hydrolysis of the ester 2,4-dinitrophenyl- ethyl methylphosphonate has been examined by both stop-flow spectrophotometric and pH-stat techniques. These reactions have been carried out in the presence of several nucleophiles including simple non-labile (w.r.t. substitution) mono-aquo metal ion complexes. Comparison of reaction rates of the metal complexes with sterically hindered organic nucleophiles has led to the conclusion that the metal ions function predominantly as general base catalysts in dilute aqueous solution. Reaction rates for the various nucleophiles studied are tabulated together with solvolysis constants for hydroxide ion and water at 35 °C and I=0.1 mol dm⁻³ (KNO₃). These later two values are respectively 32.7 mol⁻¹ dm³ s⁻¹ and 1.37 x 10⁻⁴ s⁻¹. A Brönsted β value of 0.52 for the phosphonate ester studied has also been derived.     

Synthesis,structures and reactivity of N-donor-functionalised Cu(I) aryloxides

The preparation and characterisation of the Cu(I) aryloxides [Cu₁₆(3-pyO)₁₆(dppm)₈] (1), [{Cu₂(2-pyO)₂(dppm)}₂] (2) and [{Cu₃(μ₃-6-OQ)₂(dppm)₃}{(6-HOQ)₂(μ-6-OQ)}] (3) (dppm = 1,2-bis-diphenylphosphinomethane, 6-HOQ = 6-hydroxyquinoline, py = pyridine) are described. A first attempt to employ organic anhydrides in insertion reactions with Cu(I) aryloxides was made producing the one-dimensional coordination polymer 1/_∞[Cu₃(3-pyO)(CO₂C₂H₄Boc)(dppm⁻)(dppm)]_∞ (4) (Boc = tert-butoxycarbonyl).