Until recently, computational tools were mainly used to explain chemical reactions after experimental results were obtained. With the rapid development of software and hardware technologies to make computational modeling tools more reliable, they can now provide valuable insights and even become predictive. In this review, we highlighted several studies involving computational predictions of unexpected reactivities or providing mechanistic insights for organic and organometallic reactions that led to improved experimental results. Key to these successful applications is an integration between theory and experiment that allows for incorporation of empirical knowledge with precise computed values. Computer modeling of chemical reactions is already a standard tool that is being embraced by an ever increasing group of researchers, and it is clear that its utility in predictive reaction design will increase further in the near future. 3.3.4.

The geometric and electronic structures of the aqua, chloro, acetato, hydroxo and carbonato complexes of U, Np and Pu in both their (VI) and (V) oxidation states, and in an aqueous environment, have been studied using density functional theory methods. We have obtained micro-solvated structures derived from molecular dynamics simulations and included the bulk solvent using a continuum model. We find that two different hydrogen bonding patterns involving the axial actinyl oxygen atoms are sometimes possible, and may give rise to different An-O bond lengths and vibrational frequencies. These alternative structures are reflected in the experimental An-O bond lengths of the aqua and carbonato complexes. The variation of the redox potential of the uranyl complexes with the different ligands has been studied using both BP86 and B3LYP functionals. The relative values for the four uranium complexes having anionic ligands are in surprisingly good agreement with experiment, although the absolute values are in error by approximately 1 eV. The absolute error for the aqua species is much less, leading to an incorrect order of the redox potentials of the aqua and chloro species.

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding.

Supramolecular host-guest interactions of oxazine-1 dye with β- and γ-cyclodextrins (βCD and γCD, respectively) have been investigated in neutral aqueous solution (pH ∼ 7) at ambient temperature (∼25 °C) following absorption, fluorescence, and circular dichroism measurements. The dye forms inclusion complexes with both CDs, causing significant changes in its photophysical properties. Whereas fluorescence titration data for lower dye concentrations fit well with 1:1 stoichiometric complexes, the time-resolved fluorescence results indicate formation of a small extent of 1:2 (dye-host) complexes as well, especially at higher CD concentrations. The moderate range of the binding constant values for the present systems indicates the weaker hydrophobic interaction as responsible for the inclusion complex formation in these systems. It has also been observed that γCD facilitates dimerization of the dye, prominently indicated at the higher dye concentrations. On the contrary, βCD always assists deaggregation of the dye, even at very high dye concentrations. Time-resolved fluorescence anisotropy results qualitatively support the inclusion complex formation in the present systems. Results from quantum chemical calculations also nicely corroborate with the inferences drawn from photophysical studies. Observed results demonstrate that the size compatibility of the guest and the host cavity mainly determines the host-guest interaction in the present systems, much similar to the substrate-catalyst binding in many biological systems.

The mechanism of the reduction of the hydrated uranyl cation, [UO2](2+), by the cytochromes G. sulfurreducens and D. acetoxidans has been studied using density functional theory calculations. We propose that the initial electron transfer step from the heme is to a cation-cation complex in the case of D. acetoxidans, but for G. sulfurreducens, it is to a single uranyl cation, which then forms a U(V)-U(VI) complex with a second uranyl cation. For both enzymes, the subsequent catalytic pathways are very similar. A U(V)-U(V) complex is formed, which then undergoes disproportionation via two successive protonation steps of one uranyl group, to give a U(VI)-U(IV) complex which dissociates to individual U(VI) and U(IV) species, the former being bound at the enzyme active site. Intermediate structures along the catalytic pathway are consistent with EXAFS data.

This article presents the process and mechanism of supramolecular pKa shift in two bichromophoric coumarin laser dyes, namely, coumarin 7 (C7), (ΔpK(a) = 4.6) and coumarin 30 (C30), (ΔpK(a) = 3.0), achieved by introducing a synthetic macrocyclic receptor, cucurbit[7]uril (CB7), in aqueous media. The intramolecular charge transfer, from the diethylamino coumarin moiety toward the benzimidazolyl moiety and its protonation, even at pH ∼8, is facilitated by the interaction of the cucurbituril host in a 2:1 (CB7/dye) stoichiometric ratio. The CB7 macrocycle interacts with C7/C30 dyes in a stepwise manner with binding constants of the order of K(1) ≅10(5) M(-1), K2 ≅10(4) M(-1) for both C7 and C30 dyes. This study underlines a structure-property relationship to explain the host induced changes in the stereoelectronic distributions in the guest dyes supporting the supramolecular pK(a) shifts and is appropriately established by both experimental and theoretical considerations. On the other hand, the increased solubility (>250 times) and enhancement in fluorescence intensity (>13-fold) of the coumarin dyes in the presence of CB7 also find applications for developing aqueous dye laser systems where this supramolecular strategy will largely suppress the disadvantages of low solubility, aggregation, lower emission, or low stability of the dye in aqueous medium.

A newly developed multireference (MR) ab initio method for the calculation of magnetic circular dichroism (MCD) spectra was calibrated through the calculation of the ground- and excited state properties of seven high-spin (S = 3/2) Co(II) complexes. The MCD spectra were computed by the explicit treatment of spin-orbit coupled (SOC) and spin-spin coupled (SSC) N-electron states. For the complexes studied in this work, we found that the SOC is more important than the SSC for determining the ground state zero field splitting (ZFS). Our computed ZFS parameter D for the [Co(PPh(3))(2)Cl(2)] model complex is -17.6 cm(-1), which is reasonably close to the experimental value of -14.8 cm(-1). Generally, the computed absorption and MCD spectra are in fair agreement with experiment for all investigated complexes. Thus, reliable electronic structure and spectroscopic predictions for medium sized transition metal complexes are feasible on the basis of this methodology. This characterizes the presented method as a promising tool for MCD spectra interpretations of transition metal complexes in a variety of areas of chemistry and biology.

The binding of NO to reduced myoglobin in solution results in the formation of two paramagnetic nitrosyl myoglobin (MbNO) complexes: one with a rhombic g-factor and the other with an axial one, referred to as the R- and A-forms. In spite of past extensive studies of MbNO by crystallography, spectroscopy and quantum chemical calculations it is still not clear what factors determine the appearance of the two forms. In this work we applied a combination of state of the art quantum chemical calculations and high field pulsed EPR spectroscopy (W-band, 3.4 T/95 GHz) to further characterize the two forms. Specifically, we have used (1)H and (2)H electron-nuclear double resonance (ENDOR) spectroscopy to identify and characterize the H-bond to the NO, and hyperfine sub-level correlation (HYSCORE) spectroscopy to determine the hyperfine and quadrupole interactions of the Fe(ii) coordinated (14)N of the proximal histidine (14)N(His93). The calculations employed quantum mechanics (QM), particularly density functional theory (DFT) methods in combination with molecular mechanics (MM) force-field to model the protein environment. Through QM/MM calculations of the EPR parameters we have explored their dependence on several geometrical factors of the Fe-NO bond and found those that reproduce the best experimental results. The spread of the W-band EPR spectrum of MbNO due to the g-anisotropy is large and there is a significant part of the spectrum where the R-form is the sole contributor. This allowed us to resolve some new characteristics of the R-form: (i) a NO-H hydrogen bond has been detected and characterized and through QM/MM calculations has been unambiguously assigned to (epsilon2)H(His64). (ii) The complete hyperfine and quadrupole interactions of (14)N(His93) have been determined and correlated with structural parameters again using QM/MM calculations. The agreement between the experimental results and calculations varied between excellent and good, depending on the EPR parameter in question. As for the more elusive A-form, the results only suggest that it does have a (14)N(His93) ligand with a hyperfine comparable to that of the R-form and it has less hydrogen bonding interaction with His(64). The calculations also established the orientation of the principal g-values, finding that they are closely related to the orientation of the NO bond. This information is essential for deriving structural information from the experimental orientation selective HYSCORE and ENDOR data.