X-ray crystal structure of the trifluoroacetylcobalt complex CF3COCo(CO)3(PPh3) - Implications for the relationship between structure and reactivity toward migratory insertion of carbon monoxide in cobalt alkyl complexes

In order to gain insight into the bonding in perfluoroalkyl and perfluoroacyl complexes of transition metals, the X-ray crystal structure of CF₃COCo(CO)₃(PPh₃) has been determined. Comparison of this structure with that previously reported by us for CF₃Co(CO)₃(PPh₃) and several other acyl/alkyl pairs reported by others highlights the cobalt-carbon bond contraction in the perfluoroalkyl complex and provides an explanation for why such complexes do not undergo migratory insertion of CO. Comparisons of cobalt-carbon bond lengths in hydrocarbon alkyl and acyl complexes show that the acyl complexes exhibit uniformly shorter bonds than the alkyl complexes, consistent with their ability to undergo CO insertion under mild conditions, and in contrast to the shorter Co-C bond length in the CF₃ complex relative to that in the COCF₃ species. Several other unique features of the bonding in the CF₃ complex become evident upon comparison with the CF₃CO complex and several hydrocarbon alkyl and acyl complexes. Other interesting comparisons include carbonyl stretching frequencies in the IR spectra of these complexes.     

Multiple adsorption of CO on Na-exchanged Y faujasite: a DFT investigation

Carbon monoxide is involved in many chemical and industrial processes, and its removal is of great importance to reduce detrimental environmental and climate impacts. CO is also useful to characterise the metal exchanged in zeolites. Multiple adsorption of CO in zeolite faujasites containing Na cations is investigated through quantum chemical calculations. Density functional theory (DFT) calculations were chosen to investigate the structure of sodium-exchanged cations at site II in Y faujasite and to investigate multiple CO adsorption with Na to predict the structure and the infrared CO stretching signal. DFT analysis using B3LYP, B3LYP-D and M062X showed significant differences in the coordination of Na at site II when three CO are adsorbed. From these investigations, polyadsorption of CO in NaY could lead to threefold-coordinated Na at site II in six-membered rings (6MRs) containing two Al and twofold-coordinated Na at site II in 6MRs containing one Al. These results suggest that introduction of non-bonding interactions is necessary to study polyadsorption of CO in NaY.     

Coupling of cationic olefin complexes of platinum(II) with potential ambident nucleophiles

The reactivity of [PtCl(η²-CH₂CHR)(tmeda)]⁺ (R = H, 1a, or Me, 1b; tmeda = N,N,N′,N′-tetramethyl-1,2-diaminoethane) towards some ambident nucleophiles like anilines and phenolate anion has been tested. The reaction of 1a with N-methylaniline gives immediately N-addition to the coordinated ethene (3a), but, in the presence of an inorganic carbonate, a partial rearrangement, with the para carbon of the phenyl ring taking the place of nitrogen, is observed (4a and 5a). Reaction with a tertiary aromatic amine, such as N,N-dimethylaniline, leads exclusively to the C-coupled species. The phenolate anion acts initially as an oxygen donor, however the resulting species (6a), in contact with free phenol, rearranges to C-bonded species (7a). For free phenol/6a ratios ? 5 the rearranged product has an isomeric ortho/para ratio of ≈3. For lower free phenol/6a ratios (? 1) oligomeric complexes, in which two or three platinum ethanide moieties are bound to the same phenol ring, are also formed. In the case of 1b, the above described reactivity has to compete with the base-induced deprotonation of propene, leading to formation of the allyl-bridged platinum dimer [{PtCl(tmeda)}(μ-η¹:η³-CHCHCH₂){Pt(tmeda)}]⁺. The X-ray crystal structure of 1b has also been determined; the structural parameters are very similar to those previously reported for 1a. DFT calculations have shown a similar activation of the two complexes towards nucleophilic addition at the coordinated olefin, although in 1b the electrophilic character of the olefin is masked by the Brønsted acidity of the propene methyl protons.     

Crystal structure of the novel neutral octahedral complex [(4′-(4-tbutylphenyl)-2,2′:6′,2″-terpyridine)Rh(Br)(acetonyl)2]

The synthesis and the crystal and molecular structure of a unique Rh(III) complex, [Rh^III(Br)(acetonyl)₂(4′-(4-tbutylphenyl)-2,2′:6′,2″-terpyridine)] (1) are described. The yellow crystals separate from the acetone solution of the starting complex [Rh(Br)(COD)]₂ and the ligand 4′-(4-tbutylphenyl)-2,2′:6′,2″-terpyridine after standing at room temperature for a prolonged period of time. The crystals are almost insoluble in all common organic solvents. The single-crystal X-ray structure determination shows that compound 1 is the first Rh-complex with a terdentate nitrogen ligand and two axially oriented, σ-bound acetonyl groups. DFT-calculations on a model complex without the substituent on the terpyridine ligand were carried out and agree very well with the X-ray results, confirming the constitution and geometry of the molecule.     

Competitive ligation between carbon monoxide and propiononitrile in chloro-complexes of platinum(II)

EtCN partially displaces coordinated carbon monoxide from cis-PtCl₂(CO)₂ giving an equilibrium mixture of the two geometrical isomers of PtCl₂(CO)(NCEt), together with unreacted cis-PtCl₂(CO)₂, as monitored by IR and NMR measurements. The equilibrium has also been studied starting from PtCl₂(NCEt)₂, through displacement of coordinated EtCN by CO. The equilibrium constant of the reaction between PtCl₂(CO)(NCEt) [cis + trans] and CO to produce cis-PtCl₂(CO)₂ (48 ± 6, corresponding to ΔG⁰ = −9.5 ± 0.3 kJ mol⁻¹) has been measured at 23.4 °C, in the presence of SnCl₂ as catalyst, the uncatalysed reaction being exceedingly slow. With an appropriate control of the CO partial pressure, PtCl₂(CO)(NCEt) was obtained in a nearly quantitative yield either from cis-PtCl₂(CO)₂ + EtCN or from PtCl₂(NCEt)₂ + CO. The molecular and crystal structure of cis-PtCl₂(CO)(NCEt) has been solved by X-ray diffractometry.     

[(C5H4MeEt)Ir(PPh3)2]: an agostic C-C bond or a close metal-ligand contact?

DFT calculations and orbital arguments show that the short M?C distances in the title 1,1-methylethylcyclopentadiene complex are best explained as short nonbonding contacts rather than as examples of C-C agostic bonding, as previously suggested.     

Synthesis and isocyanate insertion reactions of tungsten(IV) imido complexes formed from W(CO)(acac)(N3)(PMe3)3 with azide as the oxidant

Addition of excess trimethylphosphine and a halide source to a solution of W(CO)(acac)₂(η²-L) (L = NCPh and OCMe₂) leads to displacement of L and one acetylacetonate chelate to produce electron-rich, seven-coordinate complexes of the formula W(CO)(acac)(X)(PMe₃)₃ (X = Cl, Br, and I). Use of NaN₃ instead of a halide source leads primarily to loss of carbon monoxide and dinitrogen, and protonation from adventitious water yields the cationic imido complex [W(NH)(acac)(PMe₃)₃]⁺. Heating [W(NH)(acac)(PMe₃)₃]⁺ in aromatic isocyanates at high temperature results in isocyanate insertion into the NH imido bond to form new C-N bonds. An alternate route to related imido complexes involves heating [W(O)(acac)(PMe₃)₃]⁺ with phenyl isocyanate at high temperatures to yield the substituted imido complex [W(NPh)(acac)(PMe₃)₃]⁺.     

Reactions of triphenylphosphane-substituted ethoxycarbonylcarbene-bridged dicobalt carbonyl complexes with carbon monoxide or CO: An experimental and theoretical study

In CH₂Cl₂ solution and under a carbon monoxide atmosphere the cobalt complexes [μ₂-{ethoxycarbonyl(methylene)}-μ₂-(carbonyl)-bis(triphenylphosphanedicarbonyl-cobalt) (Co-Co)] (4) and [μ₂-{ethoxycarbonyl(methylene)}-μ₂-(carbonyl)-(tricarbonyl-cobalt)-(triphenylphosphanedicarbonyl-cobalt) (Co-Co)] (3) are in equilibrium. The equilibrium constant K = [3][PPh₃]/[4][CO] at 10 °C is 1.03 ± 0.11. The bridging and terminal CO ligands in complex 3 or 4 exchange with external ¹³CO simultaneously. In accord with that variable-temperature ¹³C NMR spectra reveal fluxional behavior for both complexes. The overall rate constant of ¹³CO-exchange for 3 at 10 °C is 17 × 10⁻³ s⁻¹ and for 4 at 10 °C is 26 × 10³ s⁻¹. In the case of complex 4 the concentration of PPh₃ has practically no influence on the rate of the ¹³CO-exchange reaction and on the rate of the reaction with CO. The coupling of the μ₂-ethoxycarbonylcarbene ligand and one of the coordinated carbon monoxide is at least one order of magnitude slower than the ¹³CO-exchange reactions, and is faster in complex 4 than in complex 3. The partial pressure of carbon monoxide has practically no effect on the coupling reaction.     

Reaction of carbon monoxide with hemocyanin: Stereochemical effects of a non-bridging ligand

The carbon monoxide binding equilibria and kinetics of a number of molluscan and arthropodal hemocyanins have been investigated employing the visible luminescence of the carbon monoxide-copper complex.Proteins from both phyla, in oligomeric and monomeric form, bind carbon monoxide non-co-operatively; the reaction is largely enthalpy driven is associated with a small unfavourable entropy change.Molluscan hemocyanins display a carbon monoxide affinity (p₅₀ = 1 to 10mm Hg) higher than that of arthropodal hemocyanins (p₅₀ = 100 to 700mm Hg), and only Panulirus interruptus hemocyanin, among those studied here, exhibits a small Bohr effect. The observed differences in equilibrium constant are kinetically reflected in differences in the carbon monoxide dissociation rate constant, which ranges from 20 to 70 s^?1 for molluscan hemocyanins and from 200 to 9000 s^?1 for arthropodal hemocyanins; on the other hand the differences in the combination rate constants between the two phyla are considerably smaller. A comparison of the equilibrium and kinetic results shows some discrepancies between the two sets of data, suggesting that carbon monoxide binding may be governed by a complex mechanism.The correlation between the ligand binding properties and the stereochemistry of the active site is discussed in the light of the knowledge that, while oxygen is bound to both copper atoms in a site, carbon monoxide is a “non-bridging” ligand, being bound to only one of the metals.     

A study on the insertion of isocyanides into palladium allyl bond: Effect of their nature on the strategic steps of the process

The coordinative capabilities of tert-butyl isocyanide (TIC) and 2,6-dimethylphenyl isocyanide (DIC) were shown to be perfectly comparable in spite of their different steric and electronic features. As a matter of fact, when equimolar amounts of these two isocyanides are made to compete for the same coordination sites of a Pd-allyl substrate the statistical mixture of the possible products is always observed.On the contrary, the DIC proved to be much more efficient than TIC in promoting the migratory insertion of an allyl fragment. This conclusion was simply based on the analysis of the products resulting from the reaction of an appropriate Pd-allyl complex with both isocyanides simultaneously.     

Examining the impact of steric and electronic variation in N2S scorpionate ligands on the properties of zinc(II) and cadmium(II) complexes

A series of LZn(II)Br (1-4) and LCd(II)Cl complexes (9-11) has been prepared by the reaction of metal halide precursors with the lithium salts of the N₂S⁻ ligands bis(3,5-diisopropylpyrazol-1-yl)dithioacetate (L¹), bis(3,5-di-tert-butylpyrazol-1-yl)dithioacetate (L²), N-phenyl-2,2-bis(3,5-diisopropylpyrazol-1-yl)thioacetamide (L³) and N-phenyl-2,2-bis(3,5-di-tert-butylpyrazol-1-yl)thioacetamide (L⁴). Characterization by X-ray crystallography and DOSY NMR studies indicate that LZnBr complexes 1-4 are mononuclear both in the solid state and in solution. Steric differences between ligands L¹-L⁴ result in distortion from an ideal tetrahedral geometry for each complex, with the degree of distortion depending on the bulk of the ligand substituents. In contrast, the related complex L³CdCl was shown by X-ray crystallography to dimerize in the solid state to form the chloride-bridged five-coordinate complex [L³CdCl]₂ (10). Despite 10 having a dinuclear structure in the solid state, DOSY NMR studies indicate 9-11 exist as mononuclear LCdCl species in solution. In addition, Zn(II) cyanide complexes of the form LZnCN [L = L¹ (5), L³ (7), L⁴ (8)] have been characterized and the X-ray structure of 8 determined. Moreover, density functional theory calculations have been conducted which yield important insight into the bonding in 1-4 and 5-8 and the electronic impact of ligands L¹-L⁴ on the zinc(II) ion and its ability to function as a Lewis acid catalyst.     

The interaction of Lewis acidic boron derivatives with Re(CO)5−nH(PMe3)n complexes

Lewis acid adducts of the hydrides cis- and trans-Re(CO)(PMe₃)₄H (1) and (2), mer-Re(CO)₂(PMe₃)₃H (3), fac-Re(CO)₂(PMe₃)₃H (4) and trans-Re(CO)₃(PMe₃)₂H (5) were studied with BH₃ and 9-borabicyclo[3,3,1] norbonane (BBNH). Using BH₃·THF and (BBNH)₂ 1 and 2 afforded Re(CO)(PMe₃)₃(η²-BH₄) (6) and Re(CO)(PMe₃)₃(η²-BBNH₂) (7) as stable and isolable products. VT IR studies established for the reaction to 7 that BBNH first attaches in a pre-equilibrium to the O_CO atom of 1 or 2. At higher temperatures ReH adduct formation occurs with instantaneous transformation to 7 and elimination of PMe₃·BBNH. In a similar way, the hydrides 3 and 4 were converted with BH₃·THF and (BBNH)₂ to yield the stable complexes Re(CO)₂(PMe₃)₂(η²-BH₄) (8) and Re(CO)₂(PMe₃)₂(η²-BBNH₂) (9). The intermediacy of the η¹-BH₄ adducts mer-/fac-Re(CO)₂(PMe₃)₃(η¹-BH₄) was confirmed by VT ¹H, ³¹P NMR and VT IR experiments. The conversion of 5 with BH₃·THF led to equilibria with adducts at the O_CO terminus in trans position to H and with H_Re as revealed by VT IR studies. Temperature dependent ³¹P equilibrium studies allowed to calculate ΔH=−4.9 kcal mol⁻¹ and ΔS=+0.034 e.u. for this reaction. These adducts could not be isolated. Compound 5 does not react with (BBNH)₂ even at elevated temperatures. DFT calculations were carried out to support the structures of the BH₃ adducts of 5. In addition a vibrational analysis helped to unravel the IR band assignments of the involved compounds. DFT calculations on 8 confirmed its C_2v structure. X-ray diffraction studies were carried out on single crystals of 6 and 7.     

Insights into mycorrhizal colonisation at elevated CO2: a simple carbon partitioning model

A simulation model was used to investigate the effect of an increased rate of plant photosynthesis at enhanced atmospheric CO2 concentration on a non-leguminous plant-mycorrhizal fungus association. The model allowed the user to modify carbon allocation patterns at three levels: (1) within the plant (shoot–root), (2) between the plant and the mycorrhizal fungus and (3) within the mycorrhizal fungus (intraradical–extraradical structures). Belowground (root and fungus) carbon losses via respiration (and turnover) could also be manipulated. The specific objectives were to investigate the dynamic nature of the potential effects of elevated CO2 on mycorrhizal colonisation and to elucidate some of the various mechanisms by which these effects may be negated. Many of the simulations showed that time (i.e. plant age) had a more significant effect on the observed stimulation of mycorrhizal colonisation by elevated CO2 than changes in carbon allocation patterns or belowground carbon losses. There were two main mechanisms which negated a stimulatory effect of elevated CO2 on internal mycorrhizal colonisation: an increased mycorrhizal carbon allocation to the external hyphal network and an increased rate of mycorrhizal respiration. The results are discussed in relation to real experiments. The need for studies consisting of multiple harvests is emphasised, as is the use of allometric analysis. Implications at the ecosystem level are discussed and key areas for future research are presented.     

Iron Se-bonded mono-selenocarbonates CpFe(CO)2SeCO2R: the first selenocarbonate complexes

The reactivity of the iron selenide complex (μ-Se)[CpFe(CO)₂]₂ toward chloroformates, ROCOCl, has been studied and the products CpFe(CO)₂SeCO₂R [R=Me (1), Et (2), iso-Bu (3), Ph (4), 2-C₆H₄Cl (5), 4-C₆H₄Cl (6), and 4-C₆H₄NO₂ (7)] have been obtained. The novel complexes, 1-7, have been characterized by elemental analyses, IR and ¹H NMR spectroscopy. The solid state structure of CpFe(CO)₂SeCO₂Et, 2, was determined by an X-ray crystal structure analysis.     

The migratory insertion of carbon monoxide in pentamethylcyclopentadienyliridium (III) complexes. Structural effects on reactivity and mechanism for rhodium and iridium systems

The reactions of complex (C₅Me₅)Ir(Cl) (CO) (Me) (1a) with cyclohexylisocyanide and phosphines (L=CyNC, PHPh₂, PMePh₂, PMe₂Ph) give the products of alkyl migratory insertion (C₅Me₅Ir(Cl) (COMe) (L), in toluence or tetrahydrofuran at 323 K or higher temperature. The phenyl analogue (C₅Me₅)Ir(Cl)(CO)(Ph) or the iodide complexes (C₅Me₅)Ir(I) (CO) (R) (R=Me, Ph_are not reactive under the same conditions. The reaction of (C₅Me₅)Ir(Cl)(CO)(Me) with PMePh₂ and PMe₂Ph in acetonitrile yields the chloride substitution product [(C₅Me₅)Ir(CO)(L)(Me)]⁺Cl⁻. Kinetic measurements for the reactions of (C₅Me₅)Ir(Cl)(CO)(Me) in toluene are first order in the iridium complex and exhibit a saturation dependence on the incoming donors L. Analysis of the data suggests a two-step process involving (i) rapid formation of a molecular complex [(C₅Me₅)Ir(Cl)(CO)(Me), (L)], in which the structure of 1a is unperturbed within the limits of spectroscopic analysis, and (ii) rate determining methyl migration. The reaction parameters are K for the pre-equilibrium step (K = 1.5 (CyNC), 7.3 (PHPh₂), 7.1 (PMePh₂) dm³ mol⁻¹ at 323 K) and k₂ for the slow carbon---carbon bond formation (k₂ (10⁵) = 6.9 (CyNC), 1.2 (PHPh₂), 1.0 (PMePh₂) s⁻¹ at 323 K). The activation parameters for the methyl migration step in the reaction with PMePh₂ obtained between 308 and 338 K, are ΔH^≠ = 106±16 kJ mol⁻¹ and ΔS^≠ = − 14±5 J K⁻¹ mol⁻¹. The reaction of 1a with PMePh₂ proceeds at similar rates in tetrahydrofuran (K = 3.7 dm³ mol⁻¹, k₂ (10⁵) = 1.2 s⁻¹, 323 K). The crystal structure of (C₅Me₅)Ir(Cl)(COMe) (PMe₂Ph) has been determined by X-ray diffraction. C₂₀H₂₉ClOPIr: M_r = 544.1, monoclinic, P2₁/n, A = 8.084 (2), B = 9.030(2), C = 28.715 (3) Å, β = 91.41 (3)°, Z = 4, D_c = 1.71 g cm⁻³, V = 2095.5 ų, room temperatyre, Mo K, γ = 0.71069, μ = 65.55 cm⁻¹, F(000) = 1044, R = 0.037 for 2453 independent observed reflections. The complex shows a deformed tetrahedral coordination assuming the η⁵-C₅Me₅ molecular fragment as a single coordination site. The iridium-chlorine bond is staggered with respect to two adjacent C(ring)-methyl bonds, while the Ir---P and the Ir---COMe bonds are eclipsed with respect to C(ring)-methyl bonds.     

Synthesis of a series of ruthenium and rhodium complexes with tridentate pyridine-based ligands containing hydrogen bonding groups

A series of ruthenium and rhodium complexes with a urea-disubstituted pyridine ligand are reported. The X-ray crystal structures of three of these species, RuCl₂(L¹)(PPh₃) (1), [Ru(MeCN)₂(L¹)(PPh₃)][BF₄]₂ (3) and Rh(CH₂Cl)Cl₂(L¹) (9) (where L¹ = N,N′-(2,2′-(1E,1′E)-(1,1′-(pyridine-2,6-diyl)bis(ethan-1-yl-1-ylidene))bis(azan-1-yl-1-ylidene)bis(ethane-2,1-diyl))diacetamide) have shown that the disubstituted pyridine acts as a tridentate ligand and its urea substituents engage in hydrogen bonding interactions with species coordinated to the metal centres. The reactivity of the ruthenium complexes towards coordination of other anions such as NCS⁻ has been investigated, as well as the oxidative-addition of alkyl chlorides to rhodium(I) centres (to yield species such as 9).     

Crystal structures of (2R,4R)-2-(polyhydroxyalkyl)-1,3-thiazolidine-4-carboxylic acids: condensation products of l-cysteine with d-hexoses

We report herein the first crystal structures of (4-carboxy-1,3-thiazolidin-2-yl)pentitols [2-(polyhydroxyalkyl)thiazolidine-4-carboxylic acids], condensation products of l-cysteine with d-galactose and d-mannose: 2-(d-galacto-pentahydroxypentyl)thiazolidine-4-carboxylic acid hydrate, Gal-Cys·H₂O (1), and 2-(d-manno-pentahydroxypentyl)thiazolidine-4-carboxylic acid hydrate, Man-Cys·H₂O (2). In 1 and 2 the compounds crystallize as zwitterions, with the carboxylic groups deprotonated and the thiazolidine N atoms protonated. The sugar moiety and carboxylate group are in a cis configuration relative to the thiazolidinium ring, which adopts different conformation: twisted (T) on C^β–S in 1, and S-puckered envelope (E) in 2. The carbon chain of the galactosyl/mannosyl moiety remains in an extended zig-zag conformation. The orientation of the sugar O2 atom with respect to the thiazolidinium S and N atoms is trans–gauche in 1 and gauche–gauche in 2. The molecular conformation is stabilized by the intramolecular N–H?O_Cys contacts in both 1 and 2 and by the additional N–H?O_Man interaction in 2. The crystal packing of orthorhombic 1 and monoclinic 2 is determined mainly by N/O/C–H?O hydrogen bonds forming ribbons linked to each other by direct and water-mediated O/C–H?O/S contacts.     

Synthesis, spectroscopy, computational evaluation and first X-ray structural characterization of a primary amine containing boronium ion

Stable (CF₃SO₂)₂N⁻, I⁻ and salts of the boronium ion [(tert-butylamine)(1-methylimidazole)BH₂]⁺ have been isolated and characterized. A single-crystal X-ray structure of the salt provides the first unambiguous proof for a boronium ion supported by a primary amine ligand.     

Reactions of [Os3(CO)10(MeCN)2] with ethynyl thiophenes: The formation of linked clusters

The reaction of 2 equiv. of [Os₃(CO)₁₀(MeCN)₂] with R-CC-L-CC-R (R = H, L = (C₄H₂S); R = SiMe₃, L = (C₄H₂S-C₄H₂S), (C₄H₂S-C₄H₂S-C₄H₂S), (C₄H₂S)-(C₁₄H₈)-(C₄H₂S)) affords the series of linked clusters [{Os₃(CO)₁₀}(HCC(C₄H₂S)CCH){Os₃(CO)₁₀}] (1), [{Os₃(CO)₁₀}(Me₃SiCC(C₄H₂S-C₄H₂S)CCSiMe₃){Os₃(CO)₁₀}] (2), [{Os₃(CO)₁₀}(Me₃SiCC(C₄H₂S-C₄H₂S-C₄H₂S)CCSiMe₃){Os₃(CO)₁₀}] (4) and [{Os₃(CO)₁₀}(Me₃SiCC(C₄H₂S)-(C₁₄H₈)-(C₄H₂S)CCSiMe₃){Os₃(CO)₁₀}] (6) as the major products. The complexes have been characterised by a range of spectroscopic methods and, in the case of 1 and 2 by single crystal X-ray crystallography. The alkyne groups cap the osmium triangles in the expected μ₃-η²-||-bonding mode and each triangle is coordinated by nine terminal and one μ₂-carbonyl group. Solution UV-Vis spectra of the complexes were similar to those observed for the free ligands consistent with there being little delocalisation between the cluster units and the thiophene groups.     

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds.