A computational study of isomeric [2.2]cyclophanes, namely [2.2]paracyclophane 1, [2.2]metacyclophane 2, and [2.2]metaparacyclophane 3, has been carried out. For 1, geometry optimizations performed by various methods at different basis sets showed that MP2/6-31+G(d,p) and B3PW91/6-31+G(d,p) provide the best results in comparison to the X-ray data. Compound 1 has D(2) symmetry with distorted bridges. A conformational search was performed for [2.2]cyclophanes 2 and 3. Each cyclophane exists in two conformations which have different energies in the case of 3 but are degenerate in the case of 2. Relative energies and strain energies at the bridges follow the same order, indicating that the relief of bridge tension and repulsion between pi clouds are determining factors for the stability of [2.2]cyclophanes. Through a decomposition of strain energy, it can be concluded that both the rings or the bridges can absorb strain, but it depends on the conformer of butane that is considered in the calculation of SE(br). Changes in aromaticity of these compounds were evaluated by NICS and HOMA and were compared with benzene and xylenes dimers as models. Despite distortions from planarity and shortening and lengthening of the C-C bonds relative to the mean, the phenyl rings are aromatic. NICS suggests a concentration of electronic density between the rings as a result of bridging process. Computed MK, NPA, and GAPT charges were compared for the isomeric cyclophanes. The GIAO chemical shifts were calculated and indicate that 1 has a larger diamagnetic anisotropy than the other isomers.

An analysis of the electron density, obtained by B3PW91/6-31+G(d,p), B3LYP/6-31+G(d,p), and MP2/6-31+G(d,p) for [2,2]cyclophanes isomers, [2.2]paracyclophane, anti-[2.2]metacyclophane, syn-[2.2]metacyclophane, and [2.2]metaparacyclophane, was made through natural bond orbitals (NBO), natural steric analysis (NSA), and atoms in molecules (AIM) methods and through analysis of frontier molecular orbitals (MOs). NBO indicates that all compounds present through-bond interactions, but only the conformers of [2.2]metacyclophane present significant through-space interactions. The last interactions are observed in AIM analysis and by the plots of MOs. AIM indicates that these through-space interactions are closed-shell ones, and they stabilize the conformers. In contrast, all isomers present through-bond and through-space repulsive interactions. In addition, the atomic properties, computed over the atomic basins, showed that the position of the bridges and the relative displacement of the rings can affect the atomic charges, the first atomic moments, and the atomic volumes.

The physical nature of the noncovalent interactions involved in anion recognition was investigated in the context of metalated calix[4]arene hosts, employing Kohn−Sham molecular orbital (KS-MO) theory, in conjunction with a canonical energy decomposition analysis, at the dispersion-corrected DFT level of theory. Computed data evidence that the most stable host−guest bonding occurs in ruthenium complexed hosts, followed by technetium and molybdenum metalated macrocyclic receptors. Furthermore, the guest's steric fit in the host scaffold is a selective and crucial criterion to the anion recognition. Our analyses reveal that coordinated charged metals provide a larger electrostatic stabilization to anion recognition, shifting the calixarenes cavity toward an electron deficient acidic character. This study contributes to the design and development of new organometallic macrocyclic hosts with increased anion recognition specificity.

chemical bonds · electrostatic interactions · hydrogen-bonded complexes · hydrogen bonds · quantum-chemical calculationsIn a recent publication by Weinhold and Klein [1] (WK) the authors report about bonding analyses of doubly charged complexes [A-HB] 2AE using the natural bond orbital (NBO) [2] method. It is claimed that the interactions between the equally charged fragments A AE ···HB AE are a manifestation of so-called "anti-electrostatic" hydrogen-bond (AEHB) complexes, where the "short-range donor-acceptor covalency forces overcome the powerful long-range electrostatic opposition to be expected between ions of like charge". WK suggest that "full recognition of the AEHB phenomenon should therefore prompt critical re-examination and reform of many aspects of current pedagogy [3] of H-bonding". They further write that "AEHB complexes may finally put to rest the superficial quasi-classical conceptions of H-bonding and other resonance-type phenomena that have too long held sway in the molecular and supramolecular sciences".We critically re-examined the claimed resonance phenomena and the electrostatic forces in one example given by WK using a more precise quantum theoretical approach for estimating the dominant interactions in the "AEHB" complexes. The chosen example is the dianion [F···HCO 3 ] 2À which exhibits a shallow minimum on the potential energy surface that is 50 kcal mol À1 higher in energy than the separated fragments F À + HCO 3 À . We took the optimized geometries at B3LYP/aug-cc-pVTZ of the equilibrium structure and the transition state for the dissociation from the work by WK. The structures are shown in Figure 1. The "AEHB" complex [F···HCO 3 ] 2À has a F-H "bond" length of 1.814 while the transition state has a slightly longer distance of 2.100 .It takes much chutzpah to use an energy-minimum structure with a well depth of 0.05(!) kcal mol À1 at B3LYP/ aug-cc-pVTZ (0.08 kcal mol À1 at MP2/aug-cc-pVTZ) [1] as object for a bonding analysis with the NBO method. But it takes a still higher degree of flippancy when the electrostatic interactions between the fragments are estimated with a formula that was proven already in 1927 [4] not to be suitable for calculating Coulombic forces between atoms at shorter region. WK write: "… for typical R A-B separations of maingroup H-bonded complexes…the Coloumbic e 2 /R potential barrier might be expected to range up to 100 kcal mol À1 or Figure 1. Calculated structures of [F···HCO 3 ] 2À at B3LYP/aug-cc-pVTZ. a) Transition state for formation of the "AEHB" complex. b) Equilibrium structure. c) Optimized structure with fixed distance R F-H = 1.50 . The coordinates for the structures shown in (a) and (b) were taken from WK.[1] Distances in ngstrçm, angles in degree. [*] Prof.

An enhanced understanding about the interactions between nanomaterials and cell membranes may have important implications for biomedical applications. In this work, coarse-grained molecular dynamics simulations of gold nanoparticles interacting with lipid bilayers were performed to evaluate the effect of hydrophobicity, charge density and ligand length on lipid bilayers. The simulations accomplished indicate that hydrophobic and anionic nanoparticles do not exhibit significant interactions and different charge densities may induce pore formation or nanoparticle wrapping, resembling first stages of endocytosis. The suggested interplay between charge density and ligand length has important implications when designing nanoparticles for drug and gene delivery applications. Moreover, control of charge densities may induce internalization of nanoparticles into cells through different mechanisms such as passive translocation, for nanoparticles with low charge density, or endocytosis for higher charge densities, highlighting the role of surface chemistry in nanoparticle-cell interactions.

The ability to create ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The administration of exogenous target-specific triggers offers the potential for traceless release of active drugs on tumor sites from antibody−drug conjugates (ADCs) and caged prodrugs. We have developed a metal-mediated bond-cleavage reaction that uses platinum complexes [K 2 PtCl 4 or Cisplatin (CisPt)] for drug activation. Key to the success of the reaction is a water-promoted activation process that triggers the reactivity of the platinum complexes. Under these conditions, the decaging of pentynoyl tertiary amides and N-propargyls occurs rapidly in aqueous systems. In cells, the protected analogues of cytotoxic drugs 5fluorouracil (5-FU) and monomethyl auristatin E (MMAE) are partially activated by nontoxic amounts of platinum salts. Additionally, a noninternalizing ADC built with a pentynoyl traceless linker that features a tertiary amide protected MMAE was also decaged in the presence of platinum salts for extracellular drug release in cancer cells. Finally, CisPt-mediated prodrug activation of a propargyl derivative of 5-FU was shown in a colorectal zebrafish xenograft model that led to significant reductions in tumor size. Overall, our results reveal a new metal-based cleavable reaction that expands the application of platinum complexes beyond those in catalysis and cancer therapy.

Quantum chemical calculations at the DFT level have been carried out for trans-[Ru II (NH 3 ) 4 (L)NO] q and trans-[Ru II (NH 3 ) 4 (L)NO] q-1 complexes, where L ) NH 3 , Cl -, and H 2 O. The equilibrium geometries and the vibrational frequencies are reported not only for the ground state (GS) but also for light-induced metastable states MS1 and MS2. The nature of the Ru-NO + and Ru-NO o bonds has been investigated by means of the energy decomposition analysis (EDA). The nature of the Ru-NO bond has been analyzed for the three states GS, MS1, and MS2, considering two different situations: before and after oneelectron reduction. The results suggest that not only the orbital term but also the ∆E Pauli term is responsible for weakening of the Ru II -NO o bond, the ∆E Pauli term increasing in comparison with the Ru II -NO + bonds, thus making the NO o ligand more susceptible to dissociation in comparison with NO + . Calculations of the Ru III -NO o species show that in this case the bonds are mainly covalent, but the electrostatic stabilization also plays an important role. Among the orbital interactions, the π-back-donation is the most important term.

2012The nature of Ru-NO bonds in ruthenium tetraazamacrocycle nitrosyl complexes-a computational study DALTON TRANSACTIONS, CAMBRIDGE, v. 41, n. 24, Ruthenium complexes including nitrosyl or nitrite complexes are particularly interesting because they can not only scavenge but also release nitric oxide in a controlled manner, regulating the NO-level in vivo.The judicious choice of ligands attached to the [RuNO] core has been shown to be a suitable strategy to modulate NO reactivity in these complexes. In order to understand the influence of different equatorial ligands on the electronic structure of the Ru-NO chemical bonding, and thus on the reactivity of the coordinated NO, we propose an investigation of the nature of the Ru-NO chemical bond by means of energy decomposition analysis (EDA), considering tetraamine and tetraazamacrocycles as equatorial ligands, prior to and after the reduction of the {RuNO} 6 moiety by one electron. This investigation provides a deep insight into the Ru-NO bonding situation, which is fundamental in designing new ruthenium nitrosyl complexes with potential biological applications.