Group 4 metal compounds incorporating the amide ligand, [N(SiMe2{C6H4-2-OMe})2](-).

The anisole-substituted silyl-amide anion, [N(SiMe2{C6H4-2-OMe})2](-) (L), has been used as a pincer-type ligand in coordination chemistry. X-ray diffraction data for the lithium salt shows a trimetallic structure consisting of two equivalents of Li(L) that sequester a molecule of LiCl. The potassium salt K(L) is dimeric in the solid-state with bridging amide ligands. Each structure shows chelation of both O-donor groups to the electropositive metal. In contrast, the titanium compound Ti(L)Cl3 is four-coordinate with a monodentate amide. The zirconium compound Zr(L)2Cl2 is monometallic with a six-coordinate metal and two N,O-bidentate amides.

Catalytic bond forming reactions promoted by amidinate, guanidinate and phosphaguanidinate compounds of magnesium.

The synthesis and catalytic properties of a series of magnesium compounds consisting of monoanionic, N,N'-chelating ligands (N∩N = amidinates, guanidinates, phosphaguanidinates) is reported. The compounds were synthesized by (i) insertion of a carbodiimide into an existing Mg-C or Mg-N bond, or (ii) protonolysis of an organomagnesium compound by a neutral pre-ligand. Structural analyses of mono- or bis-(chelate) compounds with general formula Mg(N∩N)X(L)n and Mg(N∩N)2(L)n (X = halide, aryloxide, amide; L = Et2O, THF; n = 0, 1 or 2) have been performed and the influence that the ligand substituent patterns have on the solid-state structures has been probed. Selected examples of the compounds were tested as (pre)catalysts for the polymerization of lactide, the dimerization of aldehydes and the hydroacetylenation of carbodiimides.

Catalytic hydroacetylenation of carbodiimides with homoleptic alkaline earth hexamethyldisilazides.

The homoleptic alkaline earth hexamethyldisilazides, [M{N(SiMe3)2}2(THF)2] (M = Mg 1a; Ca 1b; Sr 1c), have been shown to act as efficient precatalysts for the hydroacetylenation of organic carbodiimides with alkyl- and arylacetylenes. Catalytic activity was observed to increase with the size of the group 2 metal centre employed and to be strongly influenced by the steric properties of the carbodiimide substrate. The intermediate dimeric calcium and strontium bis(amidinate) complexes, [{PhC≡CC(N(i)Pr)2}2M]2 (M = Ca 2b, Sr 2c), have been isolated and crystallographically characterised. Kinetic studies using the strontium precursor, 1c, provided a reaction rate law independent of [acetylene] but proportional to [carbodiimide](2) and inversely proportional to the concentration of the amidine product in solution.

Reactivity of divalent germanium alkoxide complexes is in sharp contrast to the heavier tin and lead analogues.

The chemistry of ß-diketiminate germanium alkoxide complexes has been examined and shown to be in sharp contrast to its heavier congeners. For instance, (BDI)GeOR (BDI = [{N(2,6-(i)Pr(2)C(6)H(3))C(Me)}(2)CH], R = (i)Pr, (s)Bu, (t)Bu) does not react with carbon dioxide to form a metal carbonate complex. Addition of aliphatic electrophiles, such as methyl iodide or methyl triflate, results in the net oxidative addition to the germanium, giving cationic tetravalent germanium complexes, [(BDI)Ge(Me)OR][X] (X = I, OTf). An examination of the contrasting reactivities of the alkoxide ligand and the germanium loan pair with Lewis acids yielded the unusual germanium(II)-copper(I) adduct, {µ(2)-Cu(2)I(2)}[(BDI)GeO(t)Bu](2). This complex not only displays a rare example of a divalent Ge-Cu bond, but is the first example in which a planar Cu(2)I(2) diamond core possesses a three-coordinate copper bound to another metal center.

Crystalline metal (Li, Mg, Ca, Sr, Ba, Sn, Pb) complexes of the new chelating N,N'-dianionic [1,2-N(R)C6H4(CH2NR)](2-) ligand (R = SiMe3, CH2Bu(t)).

2-Aminomethylaniline was converted into the N,N'-bis(pivaloyl) (1) or -bis(trimethylsilyl) (2) derivative, using 2 Bu(t)C(O)Cl or 2 Me(3)SiCl (≡ RCl), respectively, with 2 NEt(3), or for 2 from successively using 2 LiBu(n) and 2 RCl. N,N'-Bis(neopentyl)-2-(aminomethyl)aniline (3) was prepared by LiAlH(4) reduction of 1. From 2 or 3 and 2 LiBu(n), the appropriate dilitiodiamide {2-[{N(Li)R}C(6)H(4){CH(2)N(Li)R}(L)](2) (L absent, 4a; or L = THF, 4b) or the N,N'-bis(neopentyl) analogue (5) of 4a was prepared. Treatment of 4a with 2 Bu(t)NC, 2 (2,6-Me(2)C(6)H(3)NC) or 2 Bu(t)CN (≡ L') furnished the corresponding adduct [2-N{Li(L')R}C(6)H(4){CH(2)N(Li)R}] (4c, 4d or 4e, respectively), whereas 4b with 2 PhCN afforded [2-{N(Li)R}C(6)H(4){CH(2)C(Ph) = NLi(NCPh)}] (6). The dimeric bis(amido)stannylene [Sn{N(R)C(6)H(4)(CH(2)NR)-1,2}](2) (7) was obtained from 4a and [Sn(µ-Cl)NR(2)](2), while the N,N'-bis(neopentyl) analogue 8 of 7 was similarly derived from [Sn(µ-Cl)NR(2)](2) and 5. Reaction of two equivalents of the diamine 2 with Pb(NR(2))(2) yielded 9, the lead homologue of 7. Oxidative addition of sulfur to 7 led to the dimeric bis(diamido)tin sulfide 10. Treatment of 2 successively with 'MgBu(2)' in C(5)H(12) and THF gave [Mg{N(R)C(6)H(4)(CH(2)NR)}(THF)](2) (11a), which by displacement of its THF by an equivalent portion of Bu(t)CN or PhCN produced [Mg{N(R)C(6)H(4)(CH(2)NR)}(CNR')(n)] [R' = Bu(t), n = 1 (11b); R' = Ph, n = 2 (11c)]. The Ca (12), Sr (13) or Ba (14) analogues of the Mg compound 11a were isolated from 2 and either the appropriate compound M(NR(2))(2) (M = Ca, Sr, Ba), or successively 2 LiBu(n) and 2 M(OTos)(2). The new compounds 1-14 were characterized by microanalysis (C, H, N; not for 1, 2, 3, 5), solution NMR spectra, ν(max) (C≡N) (IR for 4c, 4d, 4e, 6, 11b, 11c), selected EI-MS peaks (for 1, 2, 3, 7, 8, 9, 10), and single crystal X-ray diffraction (for 4a, 4b, 11a).

Bicyclic guanidinate compounds of magnesium and their activity as pre-catalysts in the Tishchenko reaction.

A synthetic route to magnesium guanidinate compounds that avoids ligand redistribution is reported; selected derivatives are active pre-catalysts in the dimerization of aldehydes.

Synthesis and structures of the [benzamidinato]3- complexes Li3(tmeda)(L1)]2 and [Li(thf)4][Li5(L2)(OEt2)2] [L1 = N(SiMe3)C(Ph)N(SiMe3) and L2 = N(SiMe3)C(C6H4-4)NPh].

Reduction at ambient temperature of each of the lithium benzamidinates [Li(L(1))(tmeda)] or [{Li(L(2))(OEt(2))(2)}(2)] with four equivalents of lithium metal in diethyl ether or thf furnished the brown crystalline [Li(3)(L(1))(tmeda)] (1) or [Li(thf)(4)][Li(5)(L(2))(2)(OEt(2))(2)] (2), respectively. Their structures show that in each the [N(R(1))C(R(3))NR(2)](3-) moiety has the three negative charges largely localised on each of N, N' and R = Aryl); a consequence is that the "aromatic" 2,3- and 5,6-CC bonds of R(3) approximate to being double bonds. Multinuclear NMR spectra in C(6)D(6) and C(7)D(8) show that 1 and 2 exhibit dynamic behaviour. [The following abbreviations are used: L(1) = N(SiMe(3))C(Ph)N(SiMe(3)); L(2) = N(SiMe(3))C(C(6)H(4)Me-4)N(Ph); tmeda = (Me(2)NCH(2)-)(2); thf = tetrahydrofuran.] This reduction is further supported by a DFT analysis.

Non-oxo vanadium(IV) alkoxide chemistry: solid state structures, aggregation equilibria and thermochromic behaviour in solution.

The reversible thermochromic behaviour of homoleptic [{V(OR)(4)}(n)] complexes in solution [R = Pr(i) (product I), Bu(s) (B(s)), Nep (N) and Cy (C)] is accounted for the existence of an aggregation equilibrium involving dimeric and monomeric species in which vanadium(iv) is respectively five- and four-coordinate. Bulky R groups such as Bu(t) and Pe(t) (tert-pentoxide) prevent aggregation and therefore give rise to exclusively mononuclear compounds (B(t) and P(t), respectively) that are not thermochromic. The complexes and their temperature-dependent interconversion were characterised by single crystal X-ray diffractometry, magnetic susceptibility measurements and electronic, FTIR and EPR spectroscopies in a wide temperature range. Equilibrium constants and enthalpy and entropy changes for the dimerization reactions have been determined and compared with literature data.

Activation of carbon dioxide by divalent tin alkoxides complexes.

A series of terminal tin(II) alkoxides have been synthesized utilizing the bulky ß-diketiminate ligand [{N(2,6-(i)Pr(2)C(6)H(3))-C(Me)}(2)CH] (BDI). The nucleophilicities of these alkoxides have been examined, and unexpected trends were observed. For instance, (BDI)SnOR only reacts with highly activated aliphatic electrophiles such as methyl triflate, but reacts reversibly with carbon dioxide. Both the rate of reaction and the degree of reversibility is dependent upon minor changes in the alkoxide ligand, with the bulkier tert-butoxide ligand displaying slower reactivity than the corresponding isopropyl ligand, although the latter system is a more exergonic reaction. Density Function Theory (DFT) calculations show that the differences in the reversibility of carbon dioxide insertion can be attributed to the ground-state energy differences of tin alkoxides while the rate of reaction is attributed to relative bond strengths of the Sn-O bonds. The mechanism of carbon dioxide insertion is discussed.

Carbodiimide insertion reactions of homoleptic heavier alkaline earth amides and phosphides.

A series of homoleptic guanidinate-type complexes of the heavier alkaline earth (Ae) metals calcium and strontium have been prepared. The six-coordinate compounds [Ae{(i)PrNC(NPh(2))CN(i)Pr}(2)(THF)(2)] (Ae = Ca and Sr) were synthesised through reactions of the appropriate THF-solvated hexamethyldisilazide [Ae{N(SiMe(3))(2)}(2)(THF)(2)] with two molar equivalents of diphenylamine and 1,3-di-iso-propylcarbodiimide. Both compounds were shown to crystallise with a cisoid arrangement of the two THF molecules at the metal centres. In contrast, the (Me(3)Si)(2)N-substituted calcium guanidinate, [Ca{CyNC{N(SiMe(3))(2)}CNCy}(2)(THF)(2)], contains two coordinated THF molecules with a trans disposition. Further reactions of the free amidine [{(2-FC(6)H(4))N}C(NH(i)Pr)(2)] with either [Ca{N(SiMe(3))(2)}(2)(THF)(2)] or its dimeric unsolvated analogue provided monomeric or dimeric derivatives respectively in which the ligands had tautomerised to an anisobidentate form. A further reaction of the phosphaguanidine [CyN=C(PPh(2))N(H)Cy] with [Sr{N(SiMe(3))(2)}(2)(THF)(2)] provided the first example of a phosphaguanidinate complex of this heavier alkaline earth metal. This compound has also been characterised in the solid state and shown to exist with a transoid configuration of the coordinated THF molecules.

Crystalline amidocerium(IV) oxides and a side-on bridging dioxygen complex.

Complexes [Ce(NR(2))(3)] (1) or [Ce(NR''(2))(3)] (2) were cerium(III) precursors to the X-ray characterised crystalline oligomeric oxygen-containing amidocerium(IV) compounds [{Ce(NR(2))(2)(mu-O)}(n)] (3, n = 2; 4, n = 3), [{Ce(NR''(2))(2)(mu-O)}(4)] (5), [{(R(2)N)(3)Ce}(2)(mu-[upper bond 1 start]OMOM[upper bond 1 end])] (6, M = Na; 7, M = K), [{(R(2)N)(3)CeOCe(NR(2))(2)}(2)(mu-[upper bond 1 start]OKOK[upper bond 1 end])] (8), and [{Ce(NR(2))(3)}(2)(mu-eta(2):eta(2)-O(2))].2C(n)H(2n+2) (9, n = 6; 9', n = 5) [R = SiMe(3), NR''(2) = TMP = [upper bond 1 start]NC(Me)(2)(CH(2))(3)C[upper bond 1 end]Me(2)]. Each was isolated in low, or for 5 very low, yield. Except for 4, the oxidising agent was O(2) at -27 degrees C in hexane (3, 6, 7, 8, 9), pentane (9'), or toluene (5), and a co-reagent for the alkali metal bis(trimethylsilyl)amido(oxy)cerate(iv)s was NaNR(2) (8) or KNR(2) (7, 8). From 1 and an equivalent portion of 2,6-(t)Bu(2)-benzoquinone after 5 weeks in pentane there was obtained the bis(amido)cyclotricer(IV)oxane 4. The NMR spectral solution chemical shifts for NR(2) groups of 3, 4, and 6-9 were consistent with each sample being diamagnetic and hence a Ce(IV) species. A transient amidocerium(IV) superoxide Ce(NR(2))(3)(eta(2)-O(2)) (J), or its TMP analogue, is considered to be the common first-formed intermediate in each case, while 4 is believed to have arisen from the adventitious hydrolysis of [{Ce(NR(2))(3)O}(2)((t)Bu(2)C(6)H(2)-1,4)].

Crystalline di- or trianionic metal (Al, Sm) beta-diketiminates.

The new [Al(L(Tol))Br(2)] (1) and the known [Al(L(Ph))Me(2)] (2) were prepared as potential precursors to more novel aluminium compounds. In the event, only the latter was effective. Thus 2 and two equivalents of potassium was the source of [{Al(L(Ph))Me(2)K(2)(OEt(2))}(2)] (3). The complexes [{KSm(L(Ph))(2)}(2)] (4), [Sm(2)(L(Dph))(3)] (5) and [Sm(L(Tol,Ad))(L(Tol,Ad)-H)] (6) were obtained from SmI(2) and two equivalents of the appropriate potassium beta-diketiminate [L(Ph) or L(Tol) or L(Dph) = {N(SiMe(3))C(Ar)}(2)CH, Ar = Ph or C(6)H(4)Me-4 or C(6)H(4)Ph-4; L(Tol,Ad) = N(SiMe(3))C(C(6)H(4)Me-4)C(H)C(Ad)NSiMe(3), L(Tol,Ad)-H = N(SiMe(3))C(C(6)H(4)Me-4)C(H)C(Ad)NSiMe(2)CH(2), Ad = 1-adamantyl]. Crystalline complexes 3-6 were isolated in very low (4, 5) or satisfactory (3, 6) yield and characterised by X-ray diffraction. From comparisons of the M-N, N-C, C-C and C-C(Ar) bond lengths with suitable standards, complexes 3-5 are assigned as containing Al(3+)/(L(Ph))(3-) for 3, Sm(3+)/(L(Ph))(-)/(L(Ph))(3-) for 4, and {Sm(3+)}(2)/(L(Dph))(-)/(L(Dph))(2-)/(L(Dph))(3-) for 5. Complex 6 is best formulated as a Sm(3+) compound with one "normal" (L(Tol,Ad))(-) and one deprotonated (L(Tol,Ad)-H)(2-) ligand.

Planar-chiral imidazole-based phosphine ligands derived from [2.2]paracyclophane.

Two planar chiral heteroaryl monophosphines have been synthesised and studied. The phosphines are readily prepared from 4-imidazole[2.2]paracyclophane by selective deprotonation and reaction with the appropriate dialkylchlorophosphines. The planar chiral imidazole was constructed in four steps from readily available [2.2]paracyclophane. The 2-phosphino-N-[2.2]paracyclophanes were active in the Suzuki-Miyaura coupling of aryl bromides and chlorides. Coordination studies indicate P,N-chelation in the solid-state. These studies lay the foundations for asymmetric couplings.

Coordination of neutral, methylene bridged bis-guanidyls at palladium.

The bis-guanidyl compound H(2)C{hpp}(2) (hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) coordinates to palladium(ii) as a neutral, chelating N,N'-bidentate ligand. Structural analysis of PdMeCl(H(2)C{hpp}(2)) shows a non-planar metallacycle that is twisted relative to the square plane of the metal and an "anagostic" interaction with a C-H from the bridging methylene group. Generation of the cationic palladium complex, [PdCl(H(2)C{hpp}(2))][OTf] was achieved by halide abstraction from the dichloride PdCl(2)(H(2)C{hpp}(2)) using NaOTf. The product was identified as a mixture of different species in solution; in the solid-state, the molecular structure is dimeric, consisting of the mu,mu'-dichlorobridged dication. The new bis-guanidyl compound H(2)C{tbo}(2) (Htbo = 1,4,6-triaza-bicyclo[3.3.0]oct-4-ene) was synthesized, and structurally characterized. Coordination of this compound at palladium dichloride was accompanied by ionization of the Pd-Cl bond, and formation of the dication [Pd(H(2)C{tbo}(2))(2)][Cl](2). Structural analysis shows a significant reduction in the twisting of this ligand.

Varied reactions of [M(L)]3 with HgCl2, FeBr2, CeCl3, AgOTf; ligand transfer, nucleophilic attack with recombination and/or fragmentation [M = Li or Na; L = N(SiMe3){C(H)N}3SiMe3].

The crystalline compounds [Hg{N(R)C(H)NR}(2)] (1), [Fe(L)(2)](2) (2), [Ce(L)(2)Cl](2) (3), [(AlMe(2))(3){(N(R)C(H)NC(H)N)(2)C(H)NC(H)NR}] (4), and [Ag(8)Na{(N(R)C(H)N)(2)(C(H)N)(4)R}(3)] (5) were obtained from [Li(L)](3) (A) (for 1) or [Na(L)](3) (B) and HgCl(2), FeBr(2), CeCl(3), Al(Cl)Me(2), and AgOTf, respectively [L = N(R){C(H)N}(3)R; R = SiMe(3)]. Compounds 1, 2, 3, and 5 were prepared in tetrahydrofuran (THF) at 20 degrees C; for 4, it was C(6)H(14) at -78 degrees C. NMR data for 1 showed only a single SiMe(3) environment for 1, implicating a fast exchange process. Single crystal X-ray data showed dinuclear structures for 2 and 3. Each ligand [L](-) in crystalline 2 was bound to each of the two Fe atoms in a kappa(1)- or kappa(2)-fashion, respectively, with one NSiMe(3) group of the former unattached; this was consistent with VT (1)H NMR spectral data indicative of fast exchange (at 313 K) between axial kappa(1)- and equatorial kappa(2)-N,N'-coordination to Fe. The magnetic moment for 2 in C(6)H(6) was appropriate for high-spin octahedral Fe(II). The ligands [L](-) in crystalline 3 are arranged in a helical fashion. The NMR spectra of 4 in C(6)D(5)CD(3) showed that there is an equilibrium between two asymmetric structures; minor co-products were 4', assigned as a symmetrical isomer of 4, and N(R)C(H)NR(2). The anion of 5 is proposed to be identical to that of 4'. Routes to the ligands of 1, 4, 4', and 5 are suggested; the key feature is that the ligand [L](-), unless tethered in an appropriate metal-containing matrix (as in A, B, 2, or 3), is labile because of SiMe(3) mobility, fragmentation, and/or recombination.

Superbasicity of a bis-guanidino compound with a flexible linker: a theoretical and experimental study.

The bis-guanidino compound H(2)C{hpp}(2) (I; hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) has been converted to the monocation [I-H](+) and isolated as the chloride and tetraphenylborate salts. Solution-state spectroscopic data do not differentiate the protonated guanidinium from the neutral guanidino group but suggest intramolecular "-N-H...N=" hydrogen bonding to form an eight-membered C(3)N(4)H heterocycle. Solid-state CPMAS (15)N NMR spectroscopy confirms protonation at one of the imine nitrogens, although line broadening is consistent with solid-state proton transfer between guanidine functionalities. X-ray diffraction data have been recorded over the temperature range 50-273 K. Examination of the carbon-nitrogen bond lengths suggests a degree of "partial protonation" of the neutral guanidino group at higher temperatures, with greater localization of the proton at one nitrogen position as the temperature is lowered. Difference electron density maps generated from high-resolution X-ray diffraction studies at 110 K give the first direct experimental evidence for proton transfer in a poly(guanidino) system. Computational analysis of I and its conjugate acid [I-H](+) indicate strong cationic resonance stabilization of the guanidinium group, with the nonprotonated group also stabilized, albeit to a lesser extent. The maximum barrier to proton transfer calculated using the Boese-Martin for kinetics method was 2.8 kcal mol(-1), with hydrogen-bond compression evident in the transition state; addition of zero-point vibrational energy values leads to the conclusion that the proton transfer is barrierless, implying that the proton shuttles freely between the two nitrogen atoms. Calculations determining the gas-phase proton affinity and the pK(a) in acetonitrile both indicate that compound I should behave as a superbase. This has been confirmed by spectrophotometric titrations in MeCN using polyphosphazene references, which give an average pK(a) of 28.98 +/- 0.05. Triadic analysis indicates that the dominant term causing the high basicity is the relaxation energy.

Synthesis and structures of beta-dialdiminatoantimony(III) halides and beta-dialdiminium hexahalogenoantimoniates.

From SbCl3, SbBr3 or SbI3 and an equivalent portion of the -dialdiminatopotassium compound K[{N(C6H3Pri2-2,6)C(H)}2CPh] [[triple bond]K(L)] in Et2O there was obtained in good yield the crystalline yellow [SbCl2(L)].(0.5thf).(0.5Et2O) (1) and the bis(bromo) analogue 2, or the orange [{SbI(L)(mu-I)}2].(0.5Et2O) (3). Each of 1-3 was treated with the appropriate dihalogen (X2) in Et2O. Thus, whereas 1 or 2 furnished the corresponding -dialdiminium hexahalogenoantimoniate [Et2O...H(L)H...OEt2][SbX6] (4, X = Cl; 6, X = Br), the iodo compound 3 afforded the known pyrazolium salt [N(C6H3Pri2-2,6)C(H)C(Ph)C(H)N(C6H3Pri2-2,6)][I5]. It is suggested that the source of the additional 2HX, required to convert 1 or 2 with X2 in Et2O into 4 or 6, was derived from halogenation of the N-aryl groups of L. The formation of 4 or 6 was achieved by the alternative synthesis from equivalent portions of [H2(L)]X, SbX3 and X2 in diethyl ether. The X-ray structures of the isomorphous compounds 1 and 2 and 4 and 6, as well as of 3, are reported.

Carbon dioxide activation by "non-nucleophilic" lead alkoxides.

A series of terminal lead alkoxides have been synthesized utilizing the bulky beta-diketiminate ligand [{N(2,6-(i)Pr(2)C(6)H(3))C(Me)}(2)CH](-) (BDI). The nucleophilicities of these alkoxides have been examined, and unexpected trends were observed. For instance, (BDI)PbOR reacts with methyl iodide only under forcing conditions yet reacts readily, but reversibly, with carbon dioxide. The degree of reversibility is strongly dependent upon minor changes in the R group. For instance, when R = isopropyl, the reversibility is only observed when the resulting alkyl carbonate is treated with other heterocumulenes; however, when R = tert-butyl, the reversibility is apparent upon any application of reduced pressure to the corresponding alkyl carbonate. The differences in the reversibility of carbon dioxide insertion are attributed to the ground-state energy differences of lead alkoxides. The mechanism of carbon dioxide insertion is discussed.

Galactose-conjugates of the oseltamivir pharmacophore--new tools for the characterization of influenza virus neuraminidases.

We describe the synthesis of mimetics of the alpha2-3 and alpha2-6 sialogalactoside substrates of influenza neuraminidase which include the oseltamivir pharmacophore, and report the sub-nanomolar affinities for these novel neuraminidase inhibitors. The challenge of synthesizing a Phospha-Oseltamivir/Tamiphosphor monoester involving the secondary 3-hydroxy group of galactose required to mimic the alpha2-3 sialogalactoside has been overcome by palladium-promoted coupling of the oseltamivir-derived vinyl iodide with a protected galactose-3-phosphonate. The difference in binding of these two inhibitors to a given influenza neuraminidase should be a function of its alpha2-3/alpha2-6-selectivity, an important, but not yet fully understood factor in the adaptation of highly pathogenic avian influenza viruses to human hosts.