Valerio Bertolasi

Predicting Hydrogen-Bond Strengths from Acid−Base Molecular Properties. The pKa Slide Rule: Toward the Solution of a Long-Lasting Problem

Unlike normal chemical bonds, hydrogen bonds (H-bonds) characteristically feature binding energies and contact distances that do not simply depend on the donor (D) and acceptor (:A) nature. Instead, their chemical context can lead to large variations even for a same donor-acceptor couple. As a striking example, the weak HO-H...OH(2) bond in neutral water changes, in acidic or basic medium, to the 6-fold stronger and 15% shorter [H(2)O...H...OH(2)](+) or [HO...H...OH](-) bonds. This surprising behavior, sometimes called the H-bond puzzle, practically prevents prediction of H-bond strengths from the properties of the interacting molecules. Explaining this puzzle has been the main research interest of our laboratory in the last 20 years. Our first contribution was the proposal of RAHB (resonance-assisted H-bond), a new type of strong H-bond where donor and acceptor are linked by a short pi-conjugated fragment. The RAHB discovery prompted new studies on strong H-bonds, finally leading to a general H-bond classification in six classes, called the six chemical leitmotifs, four of which include all known types of strong bonds. These studies attested to the covalent nature of the strong H-bond showing, by a formal valence-bond treatment, that weak H-bonds are basically electrostatic while stronger ones are mixtures of electrostatic and covalent contributions. The covalent component gradually increases as the difference of donor-acceptor proton affinities, DeltaPA, or acidic constants, DeltapK(a), approaches zero. At this limit, the strong and symmetrical D...H...A bonds formed can be viewed as true three-center-four-electron covalent bonds. These results emphasize the role PA/pK(a) equalization plays in strengthening the H-bond, a hypothesis often invoked in the past but never fully verified. In this Account, this hypothesis is reconsidered by using a new instrument, the pK(a) slide rule, a bar chart that reports in separate scales the pK(a)s of the D-H proton donors and :A proton acceptors most frequently involved in D-H...:A bond formation. Allowing the two scales to shift so to bring selected donor and acceptor molecules into coincidence, the ruler permits graphical evaluation of DeltapK(a) and then empirical appreciation of the D-H...:A bond strength according to the pK(a) equalization principle. Reliability of pK(a) slide rule predictions has been verified by extensive comparison with two classical sources of H-bond strengths: (i) the gas-phase dissociation enthalpies of charged [X...H...X](-) and [X...H...X](+) bonds derived from the thermodynamic NIST Database and (ii) the geometries of more than 9500 H-bonds retrieved from the Cambridge Structural Database. The results attest that the pK(a) slide rule provides a reliable solution for the long-standing problem of H-bond-strength prediction and represents an efficient and practical tool for making such predictions directly accessible to all scientists.

Self-assembly of an azido-bridged [NiII6] cluster featuring four fused defective cubanes.

The cluster [Ni6(H2L)2(HL1)2(N3)8].2C2H5OH.2H2O [1.2C2H5OH.2H2O], featuring four fused defective cubanes, has been obtained via azido-bridge-driven dimerization of two phenolate-centered trinuclear Ni3 fragments.

Resonance-assisted hydrogen bonding. III: Formation of intermolecular hydrogen-bonded chains in crystals of β-diketone enols and its relevance to molecular association

The β-diketone enol (or enolone) HO-C=C-C=O fragment produced by enolization of β-diketones is known to form strong intramolecular O-H...O hydrogen bonds where the decrease of the O...O contact distance (up to 2.40 A) is correlated with the increased π-delocalization of the O-C=C-C=O heteroconjugated system; the phenomenon has been interpreted by the resonance-assisted hydrogen-bonding (RAHB) model [Gilli, Bellucci, Ferretti & Bertolasi (1989). J. Am. Chem. Soc. 111, 1023-1028; Bertolasi, Gilli, Ferretti & Gilli (1991). J. Am. Chem. Soc. 113, 4917-1925]

Interplay between steric and electronic factors in determining the strength of intramolecular resonance-assisted NH···O hydrogen bond in a series of β-ketoarylhydrazones

The crystal structures of six β-ketoarylhydrazones are reported: 1,(Z)-2-(2-bromophenylhydrazono)-3-oxobutanenitrile; 2, (Z)-2-(2-methylphenylhydrazono)-3-oxobutanenitrile; 3, (E)-methyl-2-(2-methoxyphenylhydrazono)-3-oxobutanoate; 4, E, methyl-2-(2-cyanophenylhydrazono)-3-oxobutanoate; 5, (Z)-methyl-2-(4-cyanophenylhydrazono)-3-oxobutanoate; 6, pentane-2,3,4-trione-3-(2-carboxyphenylhydrazone). All of them form intramolecular hydrogen bonds assisted by resonance (RAHB), with N···O distances in the range 2.541(5)–2.615(3) A. These hydrogen bonds are differently affected by the substituents at the heterodienic fragment, being strengthened by electronwithdrawing substituents in position 2 (more by 2-COMe than 2-CN substitution), and weakened in β-esterhydrazones and when the N–H forms a bifurcated hydrogen bond. The role played by the different steric and electronic properties of the substituents in strengthening the H-bond is investigated, besides X-ray crystallography, by IR and 1H NMR characterization of the NH proton, and quantum mechanical DFT calculations at the B3LYP/6-31+G(d,p) level of theory on test molecules.

New μ4-Oxido-Bridged Copper Benzoate Quasi-Tetrahedron and Bis-μ3-Hydroxido-Bridged Copper Azide and Copper Thiocyanate Stepped Cubanes: Core Conversion, Structural Diversity, and Magnetic Properties

[Cu(2)(mu(4)-O)Cu(2)] and [Cu(2)(mu(3)-OH)(2)Cu(2)] geometrical arrangements are found in a new family of tetranuclear complexes: [Cu(4)(mu(4)-O)(mu-bip)(2)(mu-O(2)CPh)(4)].0.5CH(2)Cl(2) (1.0.5CH(2)Cl(2)), [Cu(4)(mu(3)-OH)(2)(mu-bip)(2)(N(3))(4)] (2), and [Cu(4)(mu(3)-OH)(2)(mu-bip)(2)(NCS)(4)(DMF)(2)] (3.2DMF) [Hbip = 2,6-bis(benzyliminomethyl)-4-methylphenol; DMF = dimethylformamide]. These complexes have been characterized by X-ray crystallography, and their magnetic properties have been studied. Complex 1 reacts with azide and thiocyanate anions, leading to 2 and 3 with a change of the [Cu(4)(mu(4)-O)] core into [Cu(4)(mu(3)-OH)(2)] units. These compounds are new examples of [Cu(4)] complexes where Cu(II) ions are connected by two types of water-derived ligands: oxide and hydroxide. Formation of these [Cu(4)] complexes can be controlled by changing the bridging ligands, which allows an effective tuning of the self-assembly. The study of the magnetic properties reveals that these complexes exhibit strong intramolecular antiferromagnetic interactions to yield a S(T) = 0 ground state. For the three complexes, the temperature dependence of the magnetic susceptibility was fitted using a model with two isolated S = 1/2 dimers based on the H = -2J{S(Cu,1).S(Cu,2)} spin Hamiltonian with J/k(B) = -289 K for 1; J/k(B) = -464 and -405 K for 2 and 3, respectively (where J is the exchange constant through the oxido-phenoxido or hydroxido-phenoxido bridges, respectively).

Associations of squaric acid and its anions as multiform building blocks of hydrogen-bonded molecular crystals

Squaric acid, H(2)C(4)O(4) (H(2)SQ), is a completely flat diprotic acid that can crystallize as such, as well as in three different anionic forms, i.e. H(2)SQ.HSQ(-), HSQ(-) and SQ(2-). Its interest for crystal engineering studies arises from three notable factors: (i) its ability of donating and accepting hydrogen bonds strictly confined to the molecular plane; (ii) the remarkable strength of the O-H...O bonds it may form with itself which are either of resonance-assisted (RAHB) or negative-charge-assisted [(-)CAHB] types; (iii) the ease with which it may donate a proton to an aromatic base which, in turn, back-links to the anion by strong low-barrier N-H+...O(1/2-) charge-assisted hydrogen bonds. Analysis of all the structures so far known shows that, while H(2)SQ can only crystallize in an extended RAHB-linked planar arrangement and SQ(2-) tends to behave much as a monomeric dianion, the monoanion HSQ(-) displays a number of different supramolecular patterns that are classifiable as beta-chains, alpha-chains, alpha-dimers and alpha-tetramers. Partial protonation of these motifs leads to H(2)SQ.HSQ(-) anions whose supramolecular patterns include ribbons of dimerized beta-chains and chains of emiprotonated alpha-dimers. The topological similarities between the three-dimensional crystal chemistry of orthosilicic acid, H(4)SiO(4), and the two-dimensional one of squaric acid, H(2)C(4)O(4), are finally stressed.

The Pivotal Role of Symmetry in the Ruthenium-Catalyzed Ring-Closing Metathesis of Olefins

The synthesis of Ru-based precatalysts with N-heterocyclic carbene (NHC) ligands bearing syn- and anti-methyl groups on the NHC backbone and aryl N-substituents with differing steric bulk was carried out. The catalytic behavior of the monophospine Ru precatalysts (7a, 7b, 8a, and 8b) was compared to the corresponding family of phosphine-free catalysts (9a, 9b, 10a and 10b) in the ring-closing metathesis (RCM) of olefins. These catalysts showed high efficiency in RCM reactions and the syn-isomers 7a and 9a, in particular, proved to be among the most active catalysts in the formation of tetrasubstituted olefins through RCM. DFT studies on the entire RCM catalytic cycle of hindered olefins were performed to rationalize the different behaviors of catalysts with syn- and anti-methyl groups on the NHC backbone. Theoretical results not only disclosed how NHC symmetry influences the overall activity of the catalyst, but also gave relevant and more general indications on the crucial steps of the RCM of olefins.

The role of the non-participating groups in substitution reactions at cationic Pt(II) complexes containing tridentate chelating nitrogen donors. Crystal structure of {Pt[bis(2-pyridylmethyl)amine](py)}(CF3SO3)2

Abstract Kinetic measurements on the displacement of chloride with the nucleophiles Br−, I− and N (N=a number of isosteric pyridines and morpholine) from the substrates [Pt(NNN)Cl]+ [NNN=bis(2-pyridylmethyl)amine (bpma); 2,6-bis(aminomethyl)pyridine (dap); diethylenetriamine (dien)] have been carried out in methanol at 25°C. The results, compared with those previously obtained on the complex [Pt(terpy)Cl]+ (terpy=2,2′:6′,2′′-terpyridine), are discussed in terms of reactivity and discrimination ability of the reaction centre. The significant differences in kinetic behaviour along the series are particularly related to the presence of pyridine rings in the non-participating chelate ligand and steric effects. The study of the reverse process, i.e. the displacement of N with a chloride ion from the complexes [Pt(NNN)(N)]2+, allows the determination of the equilibrium constants from the ratio of the rate constants. The crystal structure of [Pt(bpma)(py)](CF3SO3)2 has been determined by the X-ray diffraction technique. It consists of essentially SP (square-planar) [Pt(bpma)(py)]2+ cations. The plane through the pyridine ring makes an angle of 86.1(3)° with that of Pt and the three nitrogen atoms of bpma. The packing is characterised by a hydrogen bond between the NH of the ligand and one oxygen of a triflate anion.

Au(I)- and Pt(II)-N-heterocyclic carbene complexes with picoline functionalized benzimidazolin-2-ylidene ligands; synthesis, structures, electrochemistry and cytotoxicity studies

Novel Au(I)-N-heterocyclic carbene complexes, 1-methyl-3-(2-pyridylmethyl)-benzimidazolylidenegold(I)-chloride, 1; 1-benzyl-3-(2-pyridylmethyl)-benzimidazolylidenegold(I)chloride, 2; and Pt(II)-N-heterocyclic carbene complexes 1-methyl-3-(2-pyridylmethyl) benzimidazolylidene platinum(II)chloride, 3; and 1-benzyl-3-(2-pyridylmethyl) benzimidazolylidene platinum-(II)chloride, 4, have been synthesized, based on CN-donor proligands 1-alkyl-3-(2-pyridylmeth-yl)-benzimidazoliumchloride L1 and L2 [alkyl, R = –CH3 = L1; R = –CH2Ph = L2]. All the compounds have been synthesized and characterized by different spectroscopic methods. The Au(I) complexes 1 and 2 have been synthesized by a silver carbene transfer method. The solid-state structures of 1 and 3 have been determined by single crystal X-ray diffraction studies. The square planar Pt(II) complexes 3 and 4 show a reversible Pt(II)/Pt(IV) couple at 0.69 eV and 0.67 eV respectively. Among the complexes 1–4, complexes 1 and 3 have been used for cytotoxicity studies on the cell lines B16F10 (mouse melanoma), HepG2 (human hepatocarcinoma) and HeLa (human cervical carcinoma). IC50 values are compared with cisplatin, among 1 and 3, the Au(I) complex 1 is more effective than Pt(II) complex 3.

New Phenoxido-Bridged Quasi-Tetrahedral and Rhomboidal [Cu4] Compounds Bearing μ4-Oxido or μ1,1-Azido Ligands: Synthesis, Chemical Reactivity, and Magnetic Studies

[Cu(2)(μ(4)-O)Cu(2)] and [Cu(2)(μ(1,1)-N(3))(4)Cu(2)] geometrical arrangements are found in a new family of tetranuclear copper(II) complexes: [Cu(4)(μ(4)-O)(μ-cip)(2)Cl(4)] (1), [Cu(4)(μ(4)-O)(μ-cip)(2)(μ(1,3)-O(2)CPh)(4)]·2CH(3)OH (2·2CH(3)OH), and [Cu(4)(μ(1,1)-N(3))(4)(μ-cip)(2)(N(3))(2)]·DMF (3·DMF) [Hcip = 2,6-bis(cyclohexyliminomethylene)-4-methylphenol; CH(3)OH = methanol; DMF = dimethylformamide]. These complexes have been characterized by X-ray crystallography, and their magnetic properties have been studied. 1 and 2 form quasi-tetrahedral [Cu(4)(μ(4)-O)] complexes, and 3 is the first example of a rhomboidal [Cu(4)(μ(1,1)-N(3))] compound. Formation of the [Cu(4)] compounds is achieved via ligand-exchange reactions. The relative binding strength of the three ancillary ligands as N(3)(-) > PhCO(2)(-) > Cl(-) has been demonstrated from the core-conversion and peripheral ligand-exchange reactions. For the three complexes, the magnetic susceptibility measurements in the range of 1.8-300 K have been performed and modeled using two isolated S = (1)/(2) dimers based on the spin Hamiltonian H = -2J{S(Cu,1)·S(Cu,2)} with J/k(B) = -513, -340, and -315 K for 1-3, respectively (where J is the exchange constant through the oxido-phenoxido and azido-phenoxido bridges, respectively).