Molecular modelling for coordination compounds: Cu(II)-amine complexes

The Ligand Field Molecular Mechanics (LFMM) method has been applied to 85 Cu(II)-amine complexes, eighteen of which were selected to form a training set. A single set of parameters yields Cu-N bond lengths for four-, five- and six-coordinate systems generally within 0.04 A of their X-ray crystallographic values. Larger deviations are indicative of counterion effects and/or crystallographic artefacts arising from Jahn-Teller averaging. The LFMM treatment is flexible and unbiased and for simple ligands, automatically gives planar CuN(4) and tetragonally elongated CuN(6) complexes. In agreement with experiment, square-pyramidal coordination is marginally favoured over trigonal bipyramidal coordination for CuN(5) species. However, if the ligand requirements dictate, the LFMM accommodates trigonal bipyramidal coordination for CuN(5) species, tetrahedral distortions of CuN(4) species and cis-elongated CuN(6) species.     

DommiMOE: an implementation of ligand field molecular mechanics in the molecular operating environment

The ligand field molecular mechanics (LFMM) model, which incorporates the ligand field stabilization energy (LFSE) directly into the potential energy expression of molecular mechanics (MM), has been implemented in the "chemically aware" molecular operating environment (MOE) software package. The new program, christened DommiMOE, is derived from our original in-house code that has been linked to MOE via its applications programming interface and a number of other routines written in MOE's native scientific vector language (SVL). DommiMOE automates the assignment of atom types and their associated parameters and popular force fields available in MOE such as MMFF94, AMBER, and CHARMM can be easily extended to provide a transition metal simulation capability. Some of the unique features of the LFMM are illustrated using MMFF94 and some simple [MCl)]2- and [Ni(NH3)n]2+ species. These studies also demonstrate how density functional theory calculations, especially on experimentally inaccessible systems, provide important data for designing improved LFMM parameters. DommiMOE treats Jahn-Teller distortions automatically, and can compute the relative energies of different spin states for Ni(II) complexes using a single set of LFMM parameters.     

Molecular modelling of Jahn-Teller distortions in Cu(II)N6 complexes: elongations, compressions and the pathways in between

Ligand Field Molecular Mechanics (LFMM) parameters have been optimised for six-coordinate Cu(II) complexes containing amine, pyridine, imidazole and pyrazine donors. As found in previous LFMM applications, the new parameters automatically generate distorted structures with the magnitudes of the Jahn-Teller elongations in good agreement with experiment. Here, we explore the rest of the potential energy surface. The introduction of axial strain drives the LFMM structures via rhombic geometries to the compressed structure, the latter corresponding to the saddle point between successive elongation axes. Calculated barrier heights between compressed and elongated geometries also agree well with available experimental data. In every case bar one, the LFMM predicts that the crystallographically observed elongation axis corresponds to the overall lowest energy well. The structural predictions are confirmed by independent density functional theory (DFT) optimisations. LFMM calculations on bis(2,5-pyrazolylpyridine)copper complexes display a smooth variation in structure as a function of pyrazolyl substituent from elongated for R = H through to fully compressed for R = (t)Bu. This behaviour is driven by the steric interactions with the ground state varying smoothly as a linear combination of {d(x2-y2)}1 and {d(z2)}1.     

Stability constants: a new twist in transition metal bispidine chemistry

Transition metal complexes with 2,4-substituted tetradentate, 2,3,4- and 2,4,7-substituted pentadentate, and 2,3,4,7-substituted hexadentate bispidine ligands (bispidine = 3,7-diazabicyclo[3.3.1]nonane) with two tertiary amine and two, three, or four pyridine donors are relatively stable (10 < log K(CuL) < 18). Interestingly, the two isomeric pentadentate ligands have very different stabilities with a variety of metal ions and, depending on the metal ion, one of the isomers leads to more stable complexes than the hexadentate and the other to less stable complexes than the tetradentate ligand. Another interesting observation is that the complex stabilities of all bispidine ligands reported here do not follow the Iriving-Williams series since the stability constants of the cobalt(II) complexes are up to 4 log units larger than those of the corresponding nickel(II) complexes. All these observations are analyzed on the basis of subtle distortions of the coordination geometries, and these have been related previously to Jahn-Teller-derived distortions for the copper(II) complexes. However, similar but less pronounced structural properties are observed with other metal centers, as shown, e.g., with the experimental structures of the two zinc(II) complexes with the isomeric pentadentate ligands reported here. The structural properties and the related stabilities are also discussed on the basis of force field calculations.     

Comprehensive molecular mechanics model for oxidized type I copper proteins: active site structures, strain energies, and entatic bulging

The ligand field molecular mechanics (LFMM) model has been applied to the oxidized Type 1 copper center. In conjunction with the AMBER94 force field implemented in DommiMOE, the ligand field extension of the molecular operating environment (MOE), LFMM parameters for Cu-N(imidazole), Cu-S(thiolate), Cu-S(thioether), and Cu-O(carbonyl) interactions were developed on the basis of experimental and theoretical data for homoleptic model systems. Subsequent LFMM optimizations of the active site model complex [Cu(imidazole)2(SMe)(SMe2]+ agree with high level quantum results both structurally and energetically. Stable trigonal and tetragonal structures are located with the latter about 1.5 kcal mol-1 lower in energy. Fully optimized unconstrained structures were computed for 24 complete proteins containing T1 centers spanning four-coordinate, plastocyanin-like CuN2SS' and stellacyanin-like CuN2SO sites, plus the five-coordinate CuN2SS'O sites of the azurins. The initial structures were based on PDB coordinates augmented by a 10 A layer of water molecules. Agreement between theory and experiment is well within the experimental uncertainties. Moreover, the LFMM results for plastocyanin (Pc), cucumber basic protein (CBP) and azurin (Az) are at least as good as previously reported QM/MM structures and are achieved several orders of magnitude faster. The LFMM calculations suggest the protein provides an entatic strain of about 10 kcal mol-1. However, when combined with the intrinsic 'plasticity' of d9 Cu(II), different starting protein/solvent configurations can have a significant effect on the final optimized structure. This 'entatic bulging' results in relatively large fluctuations in the calculated metal-ligand bond lengths. For example, simply on the basis of 25 different starting configurations of the solvent molecules, the optimized Cu-S(thiolate) bond lengths in Pc vary by 0.04 A while the Cu-S(thioether) distance spans over 0.3 A. These variations are the same order of magnitude as the differences often quoted to correlate the spectroscopic properties from a set of proteins. Isolated optimizations starting from PDB coordinates (or indeed, the PDB structures themselves) may only accidentally correlate with spectroscopic measurements. The present calculations support the work of Warshel who contends that adequate configurational averaging is necessary to make proper contact with experimental properties measured in solution. The LFMM is both sufficiently accurate and fast to make this practical.     

Copper-bispidine coordination chemistry: syntheses,structures, solution properties,and oxygenation reactivity

Copper(I) and copper(II) complexes of two mononucleating and four dinucleating tetradentate ligands with a bispidine backbone (2,4-substituted (2-pyridyl or 4-methyl-2-pyridyl) 3,7-diazabicyclo[3.3.1]nonanone) have been prepared and analyzed structurally, spectroscopically, and electrochemically. The structures of the copper chromophores are square pyramidal, except for two copper(I) compounds which are four-coordinate with one noncoordinated pyridine. The other copper(I) structures have the two pyridine donors, the co-ligand (NCCH(3)), and one of the tertiary amines (N3) in-plane with the copper center and the other amine (N7) coordinated axially (Cu-N3 > Cu-N7, approximately 2.25 A vs 2.20 A). The copper(II) compounds with pyridine donors have a similar structure, but the axial amine has a weaker bond to the copper(II) center (Cu-N3 < Cu-N7, approximately 2.03 A vs 2.30 A). The structures with methylated pyridine donors are also square pyramidal with the co-ligands (Cl(-) or NCCH(3)) in-plane. With NCCH(3) the same structural type as for the other copper(II) complexes is observed, and with the bulkier Cl(-) the co-ligand is trans to N7, leading to a square pyramidal structure with the pyridine donors rotated out of the basal plane and only a small difference between axial and in-plane amines (2.15, 2.12 A). These structural differences, enforced by the rigid bispidine backbone, lead to large variations in spectroscopic and electrochemical properties and reactivities. Oxygenation of the copper(I) complexes with pyridine-substituted bispidine ligands leads to relatively stable mu-peroxo-dicopper(II) complexes; with a preorganization of the dicopper chromophores, by linking the two donor sets, these peroxo compounds are stable at room temperature for up to 1 h. The stabilization of the peroxo complexes is to a large extent attributed to the square pyramidal coordination geometry with the substrate bound in the basal plane, a structural motif enforced by the rigid bispidine backbone. The stabilities and structural properties are also seen to correlate with the spectroscopic (UV-vis and Raman) and electrochemical properties.     

Structural variation in transition-metal bispidine compounds

The experimentally determined molecular structures of 40 transition metal complexes with the tetradentate bispyridine-substituted bispidone ligand, 2,4-bis(2-pyridine)-3,7-diazabicyclo[3.3.1]nonane-9-one [M(bisp)XYZ]n+; M = CrIII, MnII, FeII, CoII, CuII, CuI, ZnII; X, Y, Z = mono- or bidentate co-ligands; penta-, hexa- or heptacoordinate complexes) are characterized in detail, supported by force-field and DFT calculations. While the bispidine ligand is very rigid (N3...N7 distance = 2.933 +/- 0.025 A), it tolerates a large range of metal-donor bond lengths (2.07 A < sigma(M-N)/4 < 2.35 A). Of particular interest is the ratio of the bond lengths between the metal center and the two tertiary amine donors (0.84 A < M-N3/M-N7 < 1.05 A) and the fact that, in terms of this ratio there seem to be two clusters with M-N3 < M-N7 and M-N3 > or = M-N7. Calculations indicate that the two structural types are close to degenerate, and the structural form therefore depends on the metal ion, the number and type of co-ligands, as well as structural variations of the bispidine ligand backbone. Tuning of the structures is of importance since the structurally differing complexes have very different stabilities and reactivities.     

Bispidine Platform Grants Full Control over Magnetic State of Ferrous Chelates in Water

A bicyclic ligand platform for iron(II), which allows total control over the complex’s magnetic properties in aqueous solution simply by varying one of the six coordination sites of the bispidine ligand, is reported. To achieve this, an efficient synthetic route to an N5 bispidine framework (ligand L4) that features an unsubstituted N‐7 site is established. Then, by choosing appropriate N‐7‐coordinating substituents, the spin state of choice can be imposed on the corresponding ferrous complexes under environmentally relevant conditions in water and near‐room temperature. Importantly, the first low‐spin and diamagnetic iron(II) chelates in the bispidine series, both in the solid state and in aqueous solution, are reported. The eradication of head‐on steric clashes between pendent coordinating arms is at the origin of this success. A new pair of constitutionally similar ferrous coordination compounds of a multidentate ligand system is obtained, which exhibits a distinctly binary (off–on) magnetic relationship. The new synthetic intermediate L4 may be substituted in just one step by any desired pendent arm, thus allowing access to complexes with finely tuned magnetic properties.     

Electronic structure of bispidine iron(IV) oxo complexes

The electronic structure, based on DFT calculations, of a range of FeIV=O complexes with two tetra- (L1 and L2) and two isomeric pentadentate bispidine ligands (L3 and L4) is discussed with special emphasis on the relative stability of the two possible spin states (S = 1, triplet, intermediate-spin, and S = 2, quintet, high-spin; bispidines are very rigid diazaadamantane-derived 3,7-diazabicyclo[3.3.1]nonane ligands with two tertiary amine and two or three pyridine donors, leading to cis-octahedral [(X)(L)FeIV=O]2+ complexes, where X = NCCH3, OH2, OH-, and pyridine, and where X = pyridine is tethered to the bispidine backbone in L3, L4). The two main structural effects are a strong trans influence, exerted by the oxo group in both the triplet and the quintet spin states, and a Jahn-Teller-type distortion in the plane perpendicular to the oxo group in the quintet state. Due to the ligand architecture the two sites for substrate coordination in complexes with the tetradentate ligands L1 and L2 are electronically very different, and with the pentadentate ligands L3 and L4, a single isomer is enforced in each case. Because of the rigidity of the bispidine ligands and the orientation of the "Jahn-Teller axis", which is controlled by the sixth donor X, the Jahn-Teller-type distortion in the high-spin state of the two isomers is quite different. It is shown how this can be used as a design principle to tune the relative stability of the two spin states.     

Factors affecting d-block metal-ligand bond lengths: toward an automated library of molecular geometry for metal complexes

Metal-ligand (M-L) bond lengths for a range of ligands (carboxylates, chlorides, pyridines, water, tertiary phosphines, and alkenes) and a variety of metals have been retrieved from the Cambridge Structural Database, CSD. Analysis of the factors which affect M-L bond lengths (for example, ligand coordination mode, oxidation state, metal coordination number and geometry, spin and Jahn-Teller effects, and ligand trans to M-L bond) shows that it is generally possible to subdivide the M-L data sets systematically to obtain better defined, unimodal, bond length distributions with means and sample standard deviations (SSDs) which reflect the nature of the bond in question. Typically, the SSDs for the M-L data sets can be reduced to 0.04-0.05 A by these methods. This work is an extension to tables of bond lengths in organometallic compounds and coordination complexes published in 1989. The importance of the factors which affect M-L bond lengths for particular metal-ligand groups are discussed. From the case studies reported, an algorithm is proposed by which compilation of a library of molecular geometry for metal complexes may be automated. The points that need to be considered to produce such a molecular library from the data stored in the CSD are discussed. The development of such a library would allow users to retrieve chemically well-defined geometric data rapidly and accurately. This should be of use, for example, to crystallographers and molecular modelers.     

Extending ligand field molecular mechanics to modelling organometallic π-bonded systems: applications to ruthenium-arenes

The ligand field molecular mechanics method has been extended to treat η(6)-arene ligands coordinated to a ruthenium(II) centre by employing a dummy atom located at the centroid of the arene ring and distributing the forces on the dummy to the arene carbon atoms. Angular overlap model parameters based on orbital energies derived from Kohn-Sham density functional theory (KS-DFT) calculations show that, relative to the Ru-dummy vector, the arene behaves as a very strong π donor and weak σ donor. Based on KS-DFT geometries, partial atomic charges and potential energy scans for a series of homoleptic and half sandwich complexes spanning arene, am(m)ine, imine, pyridyl, hydride and chloride ligands, a new LFMM force field has been developed which accurately reproduces the KS-DFT data. This FF was validated against 47 half-sandwich complexes obtained from the Cambridge Structural Database which, after minor corrections to account for the systematic errors between our chosen functional (BP86) and the experimental structures, yields a 'structurally tuned' FF where 93% of the Ru-L contacts are reproduced to 0.05 ? or better and all bar two bond lengths are within 0.1 ? of experiment. Over half the systems have non-hydrogen-atom rmsds of less than 0.5 ?. Larger differences are usually due to rotation of the arene moiety which is shown by ligand field molecular dynamics (LFMD) simulations to be an inherently low-energy process. Comparisons between LFMD and Car-Parrinello MD for [Ru(p-cymene)(ethylenediamine)Cl](+)show that LFMD is equally accurate but much faster enabling modelling of dynamic properties which occur on a timescale beyond the scope of CPMD.     

The mechanism of the (bispidine)copper(II)-catalyzed aziridination of styrene: a combined experimental and theoretical study

Experimental and DFT-based computational results on the aziridination mechanism and the catalytic activity of (bispidine)copper(I) and -copper(II) complexes are reported and discussed (bispidine=tetra- or pentadentate 3,7-diazabicyclo[3.1.1]nonane derivative with two or three aromatic N donors in addition to the two tertiary amines). There is a correlation between the redox potential of the copper(II/I) couple and the activity of the catalyst. The most active catalyst studied, which has the most positive redox potential among all (bispidine)copper(II) complexes, performs 180 turnovers in 30 min. A detailed hybrid density functional theory (DFT) study provides insight into the structure, spin state, and stability of reactive intermediates and transition states, the oxidation state of the copper center, and the denticity of the nitrene source. Among the possible pathways for the formation of the aziridine product, the stepwise formation of the two N-C bonds is shown to be preferred, which also follows from experimental results. Although the triplet state of the catalytically active copper nitrene is lowest in energy, the two possible spin states of the radical intermediate are practically degenerate, and there is a spin crossover at this stage because the triplet energy barrier to the singlet product is exceedingly high.     

Bispidine copper(II) compounds: effects of the rigid ligand backbone

Approximative density-functional theory calculations indicate that the tetradentate ligand L (L = 2,4-bis-(2-pyridyl)-3,7-diaza-[3.3.1]-bicyclononane) enforces an unusual and strong binding of a co-ligand (substrate) to a copper(II) center. The co-ligand in [Cu(L)(Cl)](+) completes a square-pyramidal coordination around copper(II) and binds in the equatorial plane rather than on the apical position. This configuration is a stable geometric isomer for the model complex [Cu(NH3)2(imine)2(Cl)](+), but it is disfavored by approximately 10 kJ mol(-1) and not commonly observed for CuN4 chromophores with a monodentate co-ligand. The equatorial coordination increases the bond energy of the copper(II)-chloride bond by approximately 80 kJ mol(-1), and similar results are expected for other copper(II)-L-substrate complexes, some of which show strong catalytic activity or unusual stability. Despite the enforced configuration, L does not impose significant steric strain on the copper(II) center but is well preorganized for the Jahn-Teller labile ion in this unusual geometry. The preorganization extends to the orientation of the pyridine donors (torsion angle around the copper-pyridine bond), and this seems to be of importance in the reactivity of the copper-L complexes and their derivatives.     

A combined experimental and computational study on the sulfoxidation by high-valent iron bispidine complexes

Iron-bispidine complexes are efficient catalysts for the oxidation of thioanisole to phenylmethylsulfoxide with iodosylbenzene as oxidant. With the tetradentate bispidine ligand L(1) (L(1) = 2,4-pyridyl-3,7-diazabicyclo[3.3.1]nonane)) the catalytic efficiency is smaller than with the pentadentate bispidine ligand L(2) (L(2) = 2,4-pyridyl-7-(pyridine-2-ylmethyl)-3,7-diazabicyclo[3.3.1]nonane)). Based on the redox potentials (iron complexes with L(1) are stronger oxidants than with L(2)) and known efficiencies in catalytic olefin oxidation and C-H activation reactions, the expectations were different. A DFT-based analysis is used to explain the apparent contradiction, and this is based on differences in the electronic ground states of the ferryl complexes as well as in the oxygen transfer transition states.     

A density functional theory study of the reaction of the biomimetic iron(II) complex of a tetradentate bispidine ligand with H2O2

Three pathways for the reaction of bispidine-iron(II) complexes (where bispidine is a rigid tetradentate amine/pyridine ligand) with H2O2 have been studied by DFT calculations. For all oxidation states the high-spin and low-spin (intermediate-spin) forms have been optimized, and the computed data have been compared with the readily available experimental results. It is concluded that there is a direct conversion of the bispidine-iron(II)-hydrogen peroxide complex to the corresponding iron(IV)-dihydroxo compound, which is a novel possible oxidant for the dihydroxylation of olefins.     

Combined ligand field and density functional theory analysis of the magnetic anisotropy in oligonuclear complexes based on Fe(III)-CN-M(II) exchange-coupled pairs

Magnetic anisotropy in cyanide-bridged single-molecule magnets (SMMs) with Fe(III)-CN-M(II) (M = Cu, Ni) exchange-coupled pairs was analyzed using a density functional theory (DFT)-based ligand field model. A pronounced magnetic anisotropy due to exchange was found for linear Fe(III)-CN-M(II) units with fourfold symmetry. This results from spin-orbit coupling of the [Fe(III)(CN)6](3-) unit and was found to be enhanced by a tetragonal field, leading to a (2)E g ground state for Fe(III). In contrast, a trigonal field (e.g., due to tau 2g Jahn-Teller angular distortions) led to a reduction of the magnetic anisotropy. A large enhancement of the anisotropy was found for the Fe(III)-CN-Ni(II) exchange pair if anisotropic exchange combined with a negative zero-field splitting energy of the S = 1 ground state of Ni(II) in tetragonally compressed octahedra, while cancellation of the two anisotropic contributions was predicted for tetragonal elongations. A recently developed DFT approach to Jahn-Teller activity in low-spin hexacyanometalates was used to address the influence of dynamic Jahn-Teller coupling on the magnetic anisotropy. Spin Hamiltonian parameters derived for linear Fe-M subunits were combined using a vector-coupling scheme to yield the spin Hamiltonian for the entire spin cluster. The magnetic properties of published oligonuclear transition-metal complexes with ferromagnetic ground states are discussed qualitatively, and predictive concepts for a systematic search of cyanide-based SMM materials are presented.     

Structure, bonding, and catecholase mechanism of copper bispidine complexes

Oxygen activation by copper(I) complexes with tetra- or pentadentate mono- or dinucleating bispidine ligands is known to lead to unusually stable end-on-[{(bispidine)Cu}(2)(O(2))](2+) complexes (bispidines are methyl-2,4-bis(2-pyridin-yl)-3,7-diazabicyclo-[3.3.1]-nonane-9-diol-1,5-dicarboxylates); catecholase activity of these dinuclear Cu(II/I) systems has been demonstrated experimentally, and the mechanism has been thoroughly analyzed. The present density functional theory (DFT) based study provides an analysis of the electronic structure and catalytic activity of [{(bispidine)Cu}(2)(O(2))](2+). As a result of the unique square pyramidal coordination geometry, the d(x(2)-y(2)) ground state leads to an unusual σ/π bonding pattern, responsible for the stability of the peroxo complex and the observed catecholase activity with a unique mechanistic pathway. The oxidation of catechol to ortho-quinone (one molecule per catalytic cycle and concomitant formation of one equivalent of H(2)O(2)) is shown to occur via an associative, stepwise pathway. The unusual stability of the end-on-peroxo-dicopper(II) complex and isomerization to copper(II) complexes with chelating catecholate ligands, which inhibit the catalytic cycle, are shown to be responsible for an only moderate catalytic activity.     

Structural origin of two paramagnetic species in six-coordinated nitrosoiron(II) porphyrins revealed by density functional theory analysis of the g tensors

Potential energy and electron paramagnetic resonance (EPR) g tensor surfaces of model five- and six-coordinated porphyrins were examined. For both types of complexes, the NO ligand is preferably coordinated end-on, with a Fe-N-O bond angle of approximately 140 degrees. In the free five-coordinated structure, NO undergoes free rotation around the axial Fe-N(NO) bond. This motion is strongly coupled to the saddle-type distortion of the porphyrin ligand. Coordination by the second axial ligand (imidazole) raises the calculated barrier for NO rotation to about 1 kcal/mol, which is further increased by displacements of imidazole from the ideal axial position. The potential energy surface for the dissociation of the weakly coordinated imidazole ligand is exceptionally flat, with variation of the Fe-N(Im) bond length between 2.1 and 2.5 A changing the energy by less than 1 kcal/mol. Experimental orientations of both axial ligands, as well as the Fe-N(Im) bond length, are therefore likely to be determined by the environment of the complex. In contrast to the total energy, calculated EPR g-tensors are sensitive to the orientation of the NO ligand and to the Fe-N(Im) bond length. Contrary to a common assumption, the g tensor component closest to the free-electron value does not coincide with the direction of the Fe-N(NO) bond. From comparison of the calculated and experimental g-tensor components for a range of structures, the rhombic ("type I") EPR signal is assigned to a static structure with NO oriented toward the meso-C atom of the prophyrin ring, and RFe-N(Im) approximately 2.1 A (calcd g1 = 1.95, g2 = 2.00, g3 = 2.04; exptl g1 = 1.96-1.98, g2 = 2.00, g3 = 2.06-2.08). The axial ("type II") EPR signal cannot correspond to any of the static structures studied presently. It is tentatively assigned to a partially dissociated six-coordinated complex (RFe-N(Im) > 2.5 A), with a freely rotating NO ligand (calcd g parallel = 2.00, g perpendicular = 2.03; exptl g parallel = 1.99-2.00, g perpendicular = 2.02-2.03).