Application des mesures de couplages 15N?H à la détermination de configurations d'oximes

Several ¹⁵N enriched oximes of heterocyclic aldehydes have been prepared in syn and anti forms. The less stable form may be obtained by UV irradiation of the other one. The geminal ¹⁵N? H coupling in the R? CH?¹⁵N? OH fragment allows an immediate and unambiguous assignment of the configuration to be made, being 13 to 16 Hz and 2 to 3 Hz for the anti and syn forms, respectively. Whereas oximes 1 to 4 are preferentially in the anti form, the N-methylpyridinium aldoxime iodides (2-PAM, 3-PAM, 4-PAM) are found to be syn in the stable form and not anti as previously thought. This reassignment is of special interest, since 2-PAM ( 8 ), which is an excellent antidote against alkyl phosphate nerve poisoning, has been used to study the geometry of the acetylcholinesterase active site of the enzyme.     

A High‐Barrier Molecular Balance for Studying Face‐to‐Face Arene–Arene Interactions in the Solid State and in Solution

An atropisomeric molecular balance was developed to study face‐to‐face arene–arene interactions. The balance has a large central 1,4,5,8‐naphthalene diimide surface that forms intramolecular arene–arene interactions with two pendent arms. The balance adopts distinct syn and anti isomers with varying numbers of intramolecular interactions. Thus, the strength of the arene–arene interaction could be quantitatively measured by NMR spectroscopy from the anti/syn ratios. The size of the arene arms was easily varied, which allowed examination of the relationship between arene size and strength of the interaction. A nonlinear size dependence was observed in solution with larger arene arms having a disproportionately stronger arene–arene interaction. The intramolecular arene–arene interactions were also characterized in the solid state by X‐ray crystallography. These studies were facilitated by the kinetic stability of the syn and anti isomers at room temperature due to the high isomerization barrier (ΔG=27.0 kcal mol^?1). Thus, the anti isomer could be selectively isolated and crystallized in its folded conformation. The X‐ray structures confirmed that the anti isomers formed two strong intramolecular arene–arene interactions with face‐to‐face geometries. The solid‐state structure analysis also reveals that the rigid framework may contribute to the observed nonlinear size trend. The acetate linker is slightly too long, which selectively destabilizes the balances with smaller arene arms. The larger arene arms are able to compensate for the longer linker and form effective intramolecular arene–arene interactions.     

Factors that regulate the conformation of m-benziporphodimethene complexes: agostic metal-arene interaction, hydrogen bonding, and η2,π coordination

Group 12 and silver(I) tetramethyl‐m‐benziporphodimethene (TMBPDM) complexes with phenyl, methylbenzoate, or nitrophenyl groups as meso substituents were synthesized and fully characterized. The dimeric silver(I) complex displays an unusual η²,π coordination from the β‐pyrrolic C?C bond to the silver ion. All of the complexes displayed a close contact between the metal ion and the inner C(22)? H(22) on the m‐phenylene ring. The downfield chemical shifts of H(22) and large coupling constants between Cd^II and H(22) strongly support the presence of an agostic interaction between the metal ion and inner C(22)–H(22). Crystal structures revealed that the syn form is the predominant conformation for TMBPDM complexes. This is distinctively different from the exclusive anti conformation observed in m‐benziporphyrin and tetraphenyl‐m‐benziporphodimethene (TPBPDM) complexes. Evidently, intramolecular hydrogen‐bonding interactions between axial chloride and methyl groups stabilize syn conformations. Unlike the merely syn conformation observed in the solid‐state structures of TMBPDM complexes that contain an axial chloride, in solution these complexes display highly solvent‐ and temperature‐dependent syn/anti ratio changes. The observation of dynamic ¹H NMR spectroscopic scrambling between syn and anti conformations from the titration of chloride ion into the solution of the TMBPDM complex suggests that axial ligand exchange is a likely pathway for the conversion between syn and anti forms. Theoretical calculations revealed that intermolecular hydrogen‐bonding interactions between the axial chloride and CHCl₃ stabilizes the anti conformation, which explains the increased ratio for the anti form when dichloromethane or chloroform was used as the solvent.     

Dispersion Interaction Stabilizes Sterically Hindered Double Fullerenes

By state‐of‐the‐art quantum chemical methods, we show that for bulky functional groups like cyclohexane, [20]fullerene, dodecahedrane, and C₆₀, the attractive dispersion interaction can have a greater impact on stereochemistry than the repulsive steric effect, making the compact isomer the more stable one. In particular, for the double C₆₀ adduct of pentacene 1 , the syn isomer should be the main product instead of the anti one inferred in the original synthesis experiment (Y. Murata et al., J. Org. Chem.­ 1999 , 64, 3483). With and without dispersion interactions taken into account, the Gibbs energy difference ΔG(syn?anti) is ?6.36 and +1.15 kcal mol^?1, respectively. This study reminds us that dispersion interactions as well as electrostatic or hyperconjugation effects, etc. can lead to some unusual stereochemical phenomena.     

Biodetergent IV. Monolayers of corynomycolic acids at the air-water interface

The effects of alkyl chain length and of differences in the length of the two alkyl chains on the formation of a monolayer of chemically synthesized corynomycolic acid (2-alkyl-3-hydroxy fatty acid) at the air-water interface were examined. Hydrophobic interactions between the two alkyl chains are required for the formation of a condensed film, which is most stable when the total number of carbon atoms in the two alkyl chains is 25 or more and the difference in their lengths is one. Syn-isomers form condensed films but usually not anti-isomers. However, films may also be formed by the anti-isomer when the alkyl chain at the carboxy group (the 2-position) is longer than the alkyl chain at the hydroxy group (the 3-position). That is, the contribution of anti-isomers to condensed film formation depends on the polar carboxy group which has greater involvement in this formation. The extrapolated area for the condensed film of corynomycolic acid was 40 Ų per molecule, thus confirming that both the carboxy and hydroxy groups are present on the water surface when a bipolar monolayer is formed.     

Experimental and Theoretical Charge Density Study on Di‐2‐pyrazylamine (Hdpza) Molecule in Crystal

Electron density distribution of Di‐2‐pyrazylamine ( Hdpza ) is studied both by single‐crystal X‐ray diffraction method at 100K and theoretical calculation. Structural determination reveals that Hdpza molecules crystalize in a syn‐anti conformation with an intramolecular C? H?N hydrogen bond between two pyrazine rings and then gather together via two intermolecular N? H?N and C? H?N hydrogen interaction and π? π stacking interaction between pyrazine rings. Charge density analysis is made in terms of deformation density (Δπ), Laplacian distribution and topological analysis of total electron density based on multipole model and theoretical calculation. The agreement between experiment and theory is good. The topological properties at bond critical points of C? C and C? N bonds reveal a covalent bond character, and those of intermolecular interactions, such as hydrogen bonds and π? π stacking interactions, reveal a closed‐shell interaction. The potential energy curve of Hdpza molecule shows that the syn‐anti conformation is the most stable one (global minima) than the other two of syn‐syn and anti‐anti conformations.     

Conformational analysis of substituted polyacetylenes

A conformational analysis of isolated chains of polymethylacetylene (PMA), polypentylacetylene (PPA), and poly(t-butylacetylene) (PTA) was carried out taking into account interactions between nonbonded atoms and torsional potentials. It was found that the trans configuration of all three polymers is more stable than the cis configuration, the difference in potential energy between the trans and the cis isomers however being very small for PTA, leading to the possibility of observing a trans^→ cis isomerization in some solvents. The calculations show that the substituted polyacetylenes are not found in a planar conformation, the larger deviations from planarity being found with the bulkier substituents: PTA > PPA > PMA. A correlation could be established between the UV absorption limit of the samples and the minimum torsional angle of the potential-energy functions. This relation predicts that the absorption limit is shifted to long wavelengths on increasing the planarity of the molecule. Moreover, UV spectra could be calculated from the potential-energy functions, and it is shown that the potential-energy functions of other substituted polyacetylenes can be calculated from their experimental UV spectra.     

Carbon-13 magnetic resonance: γ-anti substituent effects

γ-anti Substituent effects of the first row elements (CH₃, NH₂, OH, F) and the higher-row halogens on ¹³C chemical shifts are shown to have separate linear relationships with element electronegativity. The halogens generally show an increasing upfield shift with increasing electronegativity, but the response of the effect of the first-row elements to changing electronegativity is dependent upon the substitution pattern of the atoms involved. In molecules with the substituent at a bridgehead, increasing electronegativity causes increasing downfield shift of the γ-anti carbon, whereas in other systems which have the substituent at a secondary carbon, increasing electronegativity causes an increasing upfield shift. Examples are cited to show that the γ-anti effect of a hydroxyl group is more shielding (by about 2 ppm) when a 1,3-diaxial interaction between an α and a γ hydrogen is present, than when this interaction is removed by replacement of either of the hydrogens. This correlation is taken as evidence of this hydrogen-hydrogen interaction as one pathway for the transmission of the γ-anti substituent effects of first-row elements.     

Oxovanadium(IV)-Komplexe mit mehrzähnigen Aminoalkoholen als Liganden: Beziehungen zwischen Struktur und magnetischen Eigenschaften der {VO(μ-OR)2VO}-Einheit

Oxovanadium(IV) Complexes with Multidentate Amine Alcohol Ligands: Magneto-Structural Correlations for the {VO(μ-OR)₂VO} Core The trivalent, pentadentate amine alcohol ligand 1,1-bis(2-hydroxyethyl)-4-(2-hydroxybenzyl)-1,4-diazabutane (H₃hebab) reacts with [VO(acac)₂] in methanol solution to yield the binuclear oxovanadium(IV) complex [{VO(Hhebab)}₂] with a {VO(μ-OR)₂VO}²⁺ core. The compound has been characterized by vibrational (IR, Raman), UV/Vis/NIR, and ESR spectroscopy and the measurement of the magnetic susceptibility in the temperature range of 2 to 280 K. A classification is given for the correlation of the configuration of the {VO(μ-OR)₂VO} core and the magnetic properties of the related oxovanadium(IV) complexes. Antiferromagnetic interactions are operative in the case of anti-and syn-orthogonal as well as syn-coplanar configurations. whereas in the case of anti-coplanar and twist configurations ferromagnetic interactions are observed. Based on the antiferromagnetic behavior of [{VO(Hhebab)}₂] with J = ?170 cm^?1 this classification allows together with the spectroscopic data and density functional calculations the unequivocal assignment of an anti-orthogonal configuration for its {VO(μ-OR)₂VO}²⁺ core. The structural and magnetic data of a series of oxovanadium(IV) complexes with anti- and syn-orthogonal {VO(μ-OR)₂VO} core are used to investigate the quantitative correlation between the V(IV) …? V(IV) distance and the corresponding isotropic interaction constant J.     

Silver(III)⋅⋅⋅Silver(III) Interactions that Stabilize the syn Form in a Porphyrin Dimer Upon Oxidation

The interaction between two Ag^II porphyrins, connected covalently through a highly flexible ethane bridge, in a metalloporphyrin dimer has been investigated upon stepwise oxidation. X-ray structure determination of one and two-electron oxidized complexes has clearly revealed only metal-centered oxidation that results in short Ag−N (porphyrin) distance with large distortion in the porphyrin macrocycle. The 2e-oxidized complex exhibits significant metallophilic interaction in the form of a close Ag^III⋅⋅⋅Ag^III contact that brings two porphyrin rings more cofacial with syn-conformation, which would otherwise stabilize in an anti-form. The interaction also leads to an intense emission peak at 546 nm at 77 K in the photoluminescence study.     

2‐Ethyl‐6‐methylpyridin‐3‐ol and its salt bis(2‐ethyl‐3‐hydroxy‐6‐methylpyridinium) succinate

The title compounds, C₈H₁₁NO, (I), and 2C₈H₁₂NO⁺·C₄H₄O₄²⁻, (II), both crystallize in the monoclinic space group P2₁/c. In the crystal structure of (I), intermolecular O—H...N hydrogen bonds combine the molecules into polymeric chains extending along the c axis. The chains are linked by C—H...π interactions between the methylene H atoms and the pyridine rings into polymeric layers parallel to the ac plane. In the crystal structure of (II), the succinate anion lies on an inversion centre. Its carboxylate groups interact with the 2‐ethyl‐3‐hydroxy‐6‐methylpyridinium cations via intermolecular N—H...O hydrogen bonds with the pyridine ring H atoms and O—H...O hydrogen bonds with the hydroxy H atoms to form polymeric chains, which extend along the [01] direction and comprise R₄⁴(18) hydrogen‐bonded ring motifs. These chains are linked to form a three‐dimensional network through nonclassical C—H...O hydrogen bonds between the pyridine ring H atoms and the hydroxy‐group O atoms of neighbouring cations. π–π interactions between the pyridine rings and C—H...π interactions between the methylene H atoms of the succinate anion and the pyridine rings are also present in this network.     

Mechanism and structural aspects of thermal Curtius rearrangement. Quantum chemical study

The electronic and geometric structures of formyl, acetyl, and benzoyl azides were studied and fragments of the potential surfaces for the thermal Curtius rearrangement of these azides into the corresponding isocyanates were calculated by density functional theory at the PBE/TZ2P level. Acyl azides adopt two stable, conformations syn and anti, with respect to the C-N bond. The syn conformers are more stable than their anti analogs. The activation energies of the syn-anti isomerization in the series under study are 9.4, 7.0, and 9.2 kcal mol⁻¹, respectively, and the activation energies of the reverse reaction are 8.5, 6.1, and 2.5 kcal mol⁻¹. The rearrangement of syn-acyl azides is a one-step process, in which elimination of N₂ occurs synchronously with the rearrangement of atoms and bonds to form isocyanates. The activation energies of the rearrangements of syn-HC(O)N₃, syn-MeC(O)N₃, and syn-PhC(O)N₃ are 28.0, 32.9, and 34.5 kcal mol⁻¹, respectively. The rearrangement of the anti conformers of the above-mentioned azides involves the formation of singlet acylnitrene. The activation energies of the latter process are 34.6, 32.9, and 32.3 kcal mol⁻¹, respectively. The activation energies of the rearrangement of acylnitrenes into isocyanates are 20.9, 18.9, and 13.6 kcal mol⁻¹, respectively. The energy characteristics of the process and the structural data for the starting compounds, final products, and transition states provide evidence that the thermal Curtius rearrangement occurs predominantly by a concerted mechanism. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2200–2209, October, 2005.     

The search for formal electrostatic effects on molecular conformation and crystal packing: crystal structure of 2,2′′‐disubstituted (H versus PPh2) 1,1′‐(1,2‐phenylene)bis(3‐methyl‐1H‐imidazol‐3‐ium) bis(trifluoromethanesulfonate)

Electrostatic interactions between localized integral charges make the stability and structure of highly charged small and rigid organics intriguing. Can σ/π‐electron delocalization compensate reduced conformational freedom by lowering the repulsion between identical charges? The crystal structure of the title salt, C₁₄H₁₆N₄²⁺·2CF₃SO₃⁻, (2), is described and compared with that of the 2,2′′‐bis(diphenylphosphanyl) derivative, (4). The conformations of the dications and their interactions with neighbouring trifluoromethanesulfonate anions are first analyzed from the standpoint of formal electrostatic effects. Neither cation exhibits any geometrical strain induced by the intrinsic repulsion between the positive charges. In contrast, the relative orientation of the imidazolium rings [i.e. anti for (2) and syn for (4)] is controlled by different configurations of the interactions with the closest trifluoromethanesulfonate anions. The long‐range arrangement is also found to be specific: beyond the formal electrostatic packing, C—H…O and C—H…F contacts have no definite `hydrogen‐bond' character but allow the delineation of layers, which are either pleated or flat in the packing of (2) or (4), respectively.     

Interference of Copper(II) ions with Non-covalent Interactions in Uridine or Uridine 5′-Monophosphate Systems with Adenosine,Cytidine, Thymidine and their Monophosphates in Aqueous Solution

Coordination reactions of copper(II) ions and their effect on non-covalent interactions in uridine (Urd) or uridine 5′-monophosphate (UMP) systems with nucleosides (Ado, Cyd, Thd) and nucleotides (AMP and CMP) in aqueous solutions have been studied. At high pH the effective coordination centers are deprotonated N(3) atoms from Urd and Thd, whereas at low pH, the N(3) atoms of pyrimidine nucleosides are blocked for coordination and the metallation sites are endocyclic nitrogen atoms from Ado, Cyd, AMP and CMP. Moreover, at low pH, the main reaction center in nucleotide solutions is the phosphate group. The NMR study has proven the occurrence of non-covalent ion-dipole interactions and stacking interactions in the systems considered. Introduction of a copper ion in the majority of systems causes the disappearance of weak interactions between ligands. The structures of the complexes in solution have been inferred from the equilibrium study: an analysis of the pH range of their occurrence with respect to the pH range of deprotonation of particular groups in the compounds studied, using Vis, EPR and ¹³C as well as ³¹P NMR spectral analysis.     

Intramolecular Pnicogen Interactions in PHF?(CH2)n?PHF (n=2–6) Systems

A computational study of the intramolecular pnicogen bond in PHF? (CH₂)_n? PHF (n=2–6) systems was carried out. For each compound, two different conformations, (R,R) and (R,S), were considered on the basis of the chirality of the phosphine groups. The characteristics of the closed conformers, in which the pnicogen interaction occurs, were compared with those of the extended conformer. In several cases, the closed conformations are more stable than the extended conformations. The calculated interaction energies of the pnicogen contact, by means of isodesmic reactions, provide values between ?3.4 and ?26.0 kJ mol^?1. Atoms in molecules and electron localization function analysis of the electron density showed that the systems in the closed conformations with short P ??? P distances have a partial covalent character in this interaction. The calculated absolute chemical shieldings of the P atoms showed an exponential relationship with the P ??? P distance. In addition, a search in the Cambridge crystallographic database was carried out to detect those compounds with a potential intramolecular pnicogen bond in the solid phase.     

Single‐Point Remote Control of Flapping Motion in Clothespin‐Shaped Bimetallic Palladium Complexes Based on the N(sp2)–N(sp3) Interconversion in Amide Functionalities

The synthesis, structure, and flapping motion of clothespin‐shaped binuclear trans‐bis(salicylaldiminato)palladium(II) complexes (anti‐ 1 ) with 4‐azaheptamethylene linkers bearing amide ( a – g ), urethane ( h ), or urea ( i ) functionalities are described in this report. Various 2D ¹H NMR experiments and XRD analyses indicate that the amide‐ and urethane‐linked anti‐ 1 a , b , d – h complexes exist as equilibrated mixtures of major and minor conformers I and II in CDCl₃, whereas the complexes anti‐ 1 c and i were observed as a single species. The mapping of NOESY cross‐peaks between conformers I and II revealed that the equilibration of the major and minor conformers of anti‐ 1 a , b , d – h proceeds by two pathways, namely a nonrotatory flapping motion of the coordinated blades and a nonflapping rotation of C?N bonds, whereas the equilibration of anti‐ 1 c proceeds by simultaneous flapping and rotation motions. Kinetic studies carried out by means of ¹H–¹H EXSY experiments revealed that 1) the ΔG^≠_298K values for the flapping motion are controlled remotely by the steric and electronic effects of the RCON functionalities and 2) the activation parameters for the nonrotatory flapping process are identical to those for the nonflapping peptide rotation in the complexes anti‐ 1 a,b,d – h , which indicates that the present multistep conformational transformation induced by the flapping motion is controlled by the rate‐determining pyramidalization/depyramidalization (i.e., sp²/sp³ interconversion) of the nitrogen atoms of the functionalities. The static and controllable molecular mobility of anti‐ 1 bearing peptide linkers has been discussed by comparison with the dynamic behavior of its analogues anti‐ 2 – 4 with flexible polymethylene linkers.     

Conformational Stability of Propenoyl Bromide from Temperature-Dependent Infrared Spectra of Krypton Solutions,Ab Initio Calculations,and r 0 Structural Parameters of the Propenoyl Halides (F,Cl, Br)

Variable temperature (–100 to –150°C) studies of the infrared spectra (3500–400 cm^–1) of propenoyl bromide, CH₂=CHCBrO, dissolved in liquid krypton, have been carried out. Utilizing six different conformer pairs, an enthalpy difference of 204 ± 20 cm^–1 (2.44 ± 0.24 kJ/mol) was obtained, with the anti conformer (carbonyl bond trans to C=C bond) the more stable form. At ambient temperature, there is approximately 28 ± 2% of the syn conformer present. The anti conformer also remains in the infrared and Raman spectra of the polycrystalline solid. The optimal geometries, conformational stabilities, harmonic force fields, infrared intensities, Raman activities, depolarization ratios, and vibrational frequencies, are reported for both conformers from MP2/6-31G(d) ab initio calculations. The potential function governing the conformational interchange has been obtained from the MP2/6-31G(d) ab initio calculations. The conformational stabilities were calculated from a variety of basis sets and at the highest level of calculations, MP2/6-311 + (2df,2pd), the anti conformer is predicted to be more stable by 178 cm^–1, which is in excellent agreement with the experimental results. The r ₀ adjusted structural parameters have been obtained for propenoyl fluoride and chloride from a combination of the previously reported microwave rotational constants and ab initio predicted parameters. Several of the parameters for the chloride are significantly different than those proposed from an electron diffraction investigation. The results of these spectroscopic, structural, and theoretical studies are discussed and compared to the corresponding results for some similar molecules.     

Solvent effect on the syn/anti conformational stability: A comparison between conformational bias Monte Carlo and molecular dynamics methods

The solvent effect on the syn/anti population ratio of the mesityl oxide (MOx) was investigated using a new implementation of conformational bias Monte Carlo (CBMC) and molecular dynamics (MD) methods. It was observed by a previous theoretical work (Theor. Chem. Acc. (2012) 131:1214) that in gas-phase the MOx exists dominantly in syn-form and in aqueous solution in anti-form. The syn/anti free energy difference in the gas phase was used in the intramolecular parametrization and a rotational barrier of approximately 10 kcal mol⁻¹ was found. Molecular systems with barriers of this order of magnitude have been studied by experimental techniques. However, they have not been discussed yet comparing CBMC and MD simulations. In this work, we show that the intramolecular geometrical information such as bond lengths, angles and torsional angles sampled with CBMC and MD methods are equivalent. Nonetheless, only the CBMC simulations sample appropriately the syn/anti population ratio. With the CBMC configurations in gas phase, it was obtained 95% in syn-form and 5% in anti-form regardless the initial conformation. An inversion of the population was found in water, 25% in syn-form and 75% in anti-form. Comparing the gas phase and in-water CBMC sampling, it was observed that the MOx spends typically approximately 110 successive MC cycles in anti-form and approximately 2300 in syn-form in gas phase. While it was much larger with explicit water, approximately 400 times more for anti-form and approximately 6 times more for syn-form. We argue that this strong stabilization of the anti-form in aqueous solution, does not come from the MOx-water hydrogen bonds interactions, because they are the same for both conformations. Instead, the stabilization comes from the dipole-dipole interaction caused by a larger dipole moment of the MOx in the anti-form, 7.2 D, than in the syn-form, 5.2 D. With the MD sampled configurations in both conditions, we observe that the syn/anti conformational change is a very rare event due to the rotational barrier, which is approximately 17 times larger than the thermal energy. Therefore, the MD sampling of the MOx is not appropriated because it is strongly dependent on the initial conformation even for large simulations with 150 ns up to 400 ns for the isolated solute and for solute–solvent systems.     

Increasing the Bioavailability of RuIII Anticancer Complexes through Hydrophobic Albumin Interactions

A series of pyridine‐based derivatives of the clinically successful Ru^III‐based complexes indazolium [trans‐RuCl₄(1 H‐indazole)₂] (KP1019) and sodium [trans‐RuCl₄(1 H‐indazole)₂] (KP1339) have been synthesized to probe the effect of hydrophobic interactions with human serum albumin (hsA) on anticancer activity. The solution behavior and protein interactions of the new compounds were characterized by using electron paramagnetic resonance (EPR) and UV/Vis spectroscopy. These studies have revealed that incorporation of hydrophobic substituents at the 4′‐position of the axial pyridine ligand stabilizes non‐coordinate interactions with hsA. As a consequence, direct coordination to the protein is inhibited, which is expected to increase the bioavailability of the complexes, thus potentially leading to improved anticancer activity. By using this approach, the lifetimes of hydrophobic protein interactions were extended from 2 h for the unsubstituted pyridine complex, to more than 24 h for several derivatives. Free complexes were tested for their anticancer activity against the SW480 human colon carcinoma cell line, exhibiting low cytotoxicity. Pre‐treatment with hsA improved the solubility of every compound and led to some changes in activity. Particularly notable was the difference in activity between the methyl‐ and dibenzyl‐functionalized complexes. The former shows reduced activity after incubation with hsA, indicating reduced bioavailability due to protein coordination. The latter exhibits little activity on its own but, following treatment with hsA, exhibited significant cytotoxicity, which is consistent with its ability to form non‐coordinate interactions with the protein. Overall, our studies demonstrate that non‐coordinate interactions with hsA are a viable target for enhancing the activity of Ru^III‐based complexes in vivo.     

CH–π and CF–π Interactions Lead to Structural Changes of N‐Heterocyclic Carbene Palladium Complexes

The role of CH–π and CF–π interactions in determining the structure of N‐heterocyclic carbene (NHC) palladium complexes were studied using ¹H NMR spectroscopy, X‐ray crystallography, and DFT calculations. The CH–π interactions led to the formation of the cis‐anti isomers in 1‐aryl‐3‐isopropylimidazol‐2‐ylidene‐based [(NHC)₂PdX₂] complexes, while CF–π interactions led to the exclusive formation of the cis‐syn isomer of diiodobis(3‐isopropyl‐1‐pentafluorophenylimidazol‐2‐ylidene) palladium(II).