The local coupled cluster method DLPNO-CCSD(T) allows calculations on systems containing hundreds of atoms to be performed while typically reproducing canonical CCSD(T) energies with chemical accuracy. In this work, we present a scheme for decomposing the DLPNO-CCSD(T) interaction energy between two molecules into physical meaningful contributions, providing a quantification of the most important components of the chemical interaction. The method, called Local Energy Decomposition (LED), is straightforward and requires negligible additional computing time. Both the Hartree-Fock and the correlation energy are decomposed into contributions from localized or pairs of localized occupied orbitals. Assigning these localized orbitals to fragments allows one to differentiate between intra- and intermolecular contributions to the interaction energy. Accordingly, the interaction energy can be decomposed into electronic promotion, electrostatic, exchange, dynamic charge polarization, and dispersion contributions. The LED scheme is applied to a number of test cases ranging from weakly, dispersively bound complexes to systems with strong ionic interactions. The dependence of the results on the one-particle basis set and various technical aspects, such as the localization scheme, are carefully studied in order to ensure that the results do not suffer from technical artifacts. A numerical comparison between the DLPNO-CCSD(T)/LED and the popular symmetry adapted perturbation theory (DFT-SAPT) is made, and the limitations of the proposed scheme are discussed.

We definitively show that the CO stretching response to metal coordination is driven exclusively by π polarization, which quantitatively correlates with π back-donation and changes in CO bond length and frequency.

IntroductionThe induction of tolerance is central to the maintenance of immune homeostasis. Not only are dendritic cells (DCs) key elements in the development of immunity, but they also participate in the generation and maintenance of immune tolerance. Many studies have demonstrated a pivotal role for the enzyme indoleamine 2,3-dioxygenase (IDO) in immune regulation during infection, pregnancy, autoimmunity, transplantation, and neoplasia. 1,2 IDO is widely expressed in a variety of human tissues as well as in macrophages and DCs and is induced in inflammatory states via type I or type II IFN signaling. Through localized tryptophan deficiency combined with the release of proapoptotic kynurenines, DCs exert an IDO-dependent homeostatic control over the proliferation and survival of peripheral T cells and promote antigen-specific tolerance. 3,4 Murine plasmacytoid DCs (pDCs), which produce and respond to type I IFNs, have been credited with a unique ability to express functional IDO, implying an important role for these cells in the maintenance of peripheral tolerance. 5 DCs are now being exploited to improve vaccine efficacy. 6 Pathogen-pulsed DCs act, indeed, as a potent fungal vaccine in experimental hematopoietic stem cell transplantation (HSCT). 7 Protection is associated with myeloid and T-cell recovery, the activation of CD4 ϩ T-helper type 1 (Th1) lymphocytes, and the concomitant production of IL-10. This cytokine is required for the induction of regulatory T (Treg) cells, which have important functions in immune homeostasis including the onset of transplantation tolerance, inhibition of inflammation, and prevention of graft-versus-host disease (GVHD) lethality and leukemia relapse. [8][9][10] As tolerance is also one major requirement of a successful immune response to fungi, 11-13 tolerogenic DCs, including pDCs, may be pivotal in the generation of some form of dominant regulation that ultimately controls inflammation, pathogen immunity, and tolerance in transplant recipients. 14 Thymosin ␣1 (T␣1) is a naturally occurring thymic peptide 15 that promotes activation and cytokine production in human and murine mature DCs by signaling through Toll-like receptors (TLRs), including TLR9. 16 By influencing the balance of IL-12-and IL-10-producing DCs, T␣1 acts as an immune regulator capable of inducing protective immunity to Aspergillus fumigatus. 16 TLR9 stimulation can also lead to IDO activation via mechanisms including autocrine type I IFN signaling 17,18 and can promote pDC-mediated generation of CD4 ϩ CD25 ϩ cells, 19 which are an essential component of the IDO-dependent protective immunity to fungi. [11][12][13] We hypothesized that T␣1 could affect the balance of immunity and tolerance by DCs and the generation of Treg cells. We assessed here the effects of T␣1 on deriving DCs from bone marrow (murine) or peripheral blood (human) L.R. and P.P. devised the study, critically evaluated the data at regular intervals, and drafted the paper. L.R. takes responsibility for integrity of the work as a whole. K.P....

The domain-based local pair natural orbital (PNO) coupled-cluster DLPNO-CCSD(T) method allows one to perform single point energy calculations for systems with hundreds of atoms while retaining essentially the accuracy of its canonical counterpart, with errors that are typically smaller than 1 kcal/mol for relative energies. Crucial to the accuracy and efficiency of the method is a proper definition of the virtual space in which the coupled-cluster equations are solved, which is spanned by a highly compact set of pair natural orbitals (PNOs) that are specific for each electron pair. The dimension of the PNO space is controlled by the T CutPNO threshold: only PNOs with an occupation number greater than T CutPNO are included in the correlation space of a given electron pair, whilst the remaining PNOs are discarded. To keep the error of the method small, a conservative T CutPNO value is used in standard DLPNO-CCSD(T) calculations. This often leads to unnecessarily large PNO spaces, which limits the efficiency of the method. Herein, we introduce a new computational strategy to approach the complete PNO space limit (for a given basis set) that consists in extrapolating the results obtained with different T CutPNO values. The method is validated on the GMTKN55 set using canonical CCSD(T) data as the reference. Our results demonstrate that a simple two-point extrapolation scheme can be used to significantly increase the efficiency and accuracy of DLPNO-CCSD(T) calculations, thus extending the range of applicability of the technique.

The development of post-Hartree−Fock (post-HF) energy decomposition schemes that are able to decompose the HF and correlation components of the interaction energy into chemically meaningful contributions is a very active field of research. One of the challenges is to provide a clear-cut quantification to the elusive London dispersion component of the intermolecular interaction. London dispersion is well-known to be a pure correlation effect, and as such it is not properly described by mean field theories. In this context, we have recently developed the local energy decomposition (LED) analysis, which provides a chemically meaningful decomposition of the interaction energy between two or more fragments computed at the domain-based local pair natural orbitals coupled cluster (DLPNO-CCSD(T)) level of theory. In this work, this scheme is used in conjunction with other interpretation tools to study a series of molecular adducts held together by intermolecular interactions of different natures. The HF and correlation components of the interaction energy are thus decomposed into a series of chemically meaningful contributions. Emphasis is placed on discussing the physical effects associated with the inclusion of electron correlation. It is found that four distinct physical effects can contribute to the magnitude of the correlation part of intermolecular binding energies (ΔE int C ): (i) London dispersion, (ii) the correlation correction to the reference induction energy, (iii) the correlation correction to the electron sharing process, and (iv) the correlation correction to the permanent electrostatics. As expected, the largest contribution to the correlation binding energy of neutral, apolar molecules is London dispersion, as in the argon dimer case. In contrast, the correction for the HF induction energy dominates ΔE int C in systems in which an apolar molecule interacts with charged or strongly polar species, as in Ar−Li + . This effect has its origin in the systematic underestimation of polarizabilities at the HF level of theory. For similar reasons, electron sharing largely contributes to the correlation binding energy of covalently bound molecules, as in the beryllium dimer case. Finally, the correction for HF permanent electrostatics significantly contributes to ΔE int C in molecules with strong dipoles, such as water and hydrogen fluoride dimers. This effect originates from the characteristic overestimation of dipole moments at the HF level of theory, leading in some cases to positive ΔE int C values. Our results are apparently in contrast to the widely accepted view that ΔE int C is typically dominated by London dispersion, at least, in the strongly interacting region. Clearly, post-HF energy decomposition schemes are very powerful tools to analyze, categorize, and understand the various contributions to the intermolecular interaction energy. Hopefully, this will eventually lead to insights that are helpful in designing systems with tailored properties. All analysis tools presented in this work will be availabl...

Local energy decomposition (LED) analysis decomposes the interaction energy between two fragments calculated at the domain-based local pair natural orbital CCSD(T) (DLPNO-CCSD(T)) level of theory into a series of chemically meaningful contributions and has found widespread applications in the study of noncovalent interactions. Herein, an extension of this scheme that allows for the analysis of interaction energies of open-shell molecular systems calculated at the UHF-DLPNO-CCSD(T) level is presented. The new scheme is illustrated through applications to the CH 2 ···X (X = He, Ne, Ar, Kr, and water) and heme···CO interactions in the low-lying singlet and triplet spin states. The results are used to discuss the mechanism that governs the change in the singlet–triplet energy gap of methylene and heme upon adduct formation.

The interaction of Lewis acids and bases in both classical Lewis adducts and frustrated Lewis pairs (FLPs) is investigated to elucidate the role that London dispersion plays in different situations. The analysis comprises 14 different adducts between tris(pentafluorophenyl)borane and a series of phosphines, carbenes, and amines with various substituents, differing in both steric and electronic properties. The domain-based local pair natural orbital coupled-cluster (DLPNO-CCSD(T)) method is used in conjunction with the recently introduced local energy decomposition (LED) analysis to obtain state-of-the-art dissociation energies and, at the same time, a clear-cut definition of the London dispersion component of the interaction, with the ultimate goal of aiding in the development of designing principles for acid/base pairs with well-defined bonding features and reactivity. In agreement with previous DFT investigations, it is found that the London dispersion dominates the interaction energy in FLPs, and is also remarkably strong in Lewis adducts. In these latter systems, its magnitude can be easily modulated by modifying the polarizability of the substituents on the basic center, which is consistent with the recently introduced concept of dispersion energy donors. By counteracting the destabilizing energy contribution associated with the deformation of the monomers, the London dispersion drives the stability of many Lewis adducts.

We recently devised a simple scheme for analyzing on quantitative grounds the Dewar-Chatt-Duncanson donation and back-donation in symmetric coordination complexes. Our approach is based on a symmetry decomposition of the so called Charge-Displacement (CD) function quantifying the charge flow, upon formation of a metal (M)-substrate (S) bond, along the M-S interaction axis and provides clear-cut measures of donation and back-donation charges in correlation with experimental observables [G. Bistoni et al., Angew. Chem., Int. Ed. 52, 11599 (2013)]. The symmetry constraints exclude of course from the analysis most systems of interest in coordination chemistry. In this paper, we show how to entirely overcome this limitation by taking advantage of the properties of the natural orbitals for chemical valence [M. Mitoraj and A. Michalak, J. Mol. Model. 13, 347 (2007)]. A general scheme for disentangling donation and back-donation in the CD function of both symmetric and non-symmetric systems is presented and illustrated through applications to M-ethyne (M = Au, Ni and W) coordination bonds, including an explicative study on substrate activation in a model reaction mechanism.