Pair Natural Orbital Coupled Cluster Research Articles

Structure prediction of physiological bis(amino acidato)copper(II) species in aqueous solution: The copper(II) compounds with l-glutamine and l-histidine

Neutral (l-histidinato)(l-glutaminato)copper(II) [Cu(His)(Gln)] has been established as the most abundant ternary copper(II) amino acid compound of the exchangeable copper(II) pool in blood plasma. The experimental studies of Cu(His)(Gln) and bis(glutaminato)copper(II) [Cu(Gln)2] in solutions did not specify their complete geometries. To determine the geometries, this paper investigates the conformers, energy landscapes, and a structure–magnetic parameters relation of Cu(Gln)2 and Cu(His)(Gln) by the density functional theory (DFT) calculations. We assume a glycine-like coordination of Gln (other coordination patterns are dismissed because of steric reasons), and three His in-plane copper(II) binding modes. The conformational analyses are performed in the gas phase and implicitly modeled aqueous solution. The reliability of the DFT relative electronic and Gibbs free energies of the Cu(His)(Gln) conformers is confirmed by benchmarking against the corresponding energies obtained by the domain-based local pair natural orbital coupled-cluster method with singles, doubles, and perturbative triples [DLPNO-CCSD(T)]. Several cis- and trans-Cu(His)(Gln) conformers with His in the histaminate-like and glycine-like modes have low Gibbs free energies, and the greatest estimated metal-binding affinities. The DFT-calculated magnetic parameters of the low-energy conformers reproduce best the experimental electron paramagnetic resonance parameters measured in aqueous solutions for trans- and cis-Cu(Gln)2 conformers having two oxygen atoms (either from Gln or water molecules) at the apical positions, and Cu(His)(Gln) conformers having His in the histaminate-like mode with an apically placed carboxylato oxygen atom. The predicted conformational flexibility of His‑copper(II)-amino acid compounds may be connected with their physiological abundance, and the role in copper(II) exchange reactions in blood plasma.

Phase equilibria modeling of cross-associating systems guided by a quantum chemical multi-conformational framework

Cross-association between molecules may result in several conformations of weakly bound molecular complexes with different association energies. However, the conventional combining rules used in equations of state account only for one conformation. Therefore, in the present work we introduce a framework that allows one to distinguish the cross-interactions between sites of different nature and to expand the number of captured conformations coexisting in the mixture. We incorporated the proposed approach into the Cubic-Plus-Association (CPA) equation of state and applied it to model the binary Vapor-Liquid Equilibrium (VLE) of aqueous mixtures with alcohols (methanol, ethanol, propan-2-ol, tert-butanol, and phenol), acetic acid, and CO2. For the mixtures with alcohols, we report the quantum chemical association energies calculated with the benchmark Domain-Based Local Pair Natural Orbital Coupled-Cluster Single, Double, and Perturbative Triple DLPNO-CCSD(T) approach and compare these values with association energies obtained by fitting to experimental data using a distinguishable interactions approach. Based on the updated results for the binary systems, we investigated how the new cross-association parameters will affect the predictions of the ternary Liquid-Liquid Equilibrium (LLE) of water–alcohol–hydrocarbon mixtures and VLE of water–acetic acid–CO2 mixtures.

Bond-Dissociation Energies to Probe Pyridine Electronic Effects on Organogold(III) Complexes: From Methodological Developments to Application in π-Backdonation Investigation and Catalysis.

In this work, we report on the synthesis of several organogold(III) complexes based on 4,4'-diterbutylbiphenyl (C^C) and 2,6-bis(4-terbutylphenyl)pyridine (C^N^C) ligands and bond with variously substituted pyridine ligands (pyrR). Altogether, 33 complexes have been prepared and studied with mass spectrometry using higher-energy collision dissociation (HCD) in an Orbitrap mass spectrometer. A complete methodology including the kinetic modeling of the dissociation process based on the Rice-Ramsperger-Kassel-Marcus (RRKM) statistical method is proposed to obtain critical energies E0 of the pyrR loss for all complexes. The capacity of these E0 values to describe the pyridine ligand effect is further explored, at the same time as more classical descriptors such as 1H pyridinic NMR shift variation upon coordination and Au-NpyrR bond length measured by X-ray diffraction. An extensive theoretical work, including density functional theory (DFT) and domain-based local pair natural orbital coupled-cluster theory (DLPNO-CCSD(T)) methods, is also carried out to provide bond-dissociation energies, which are compared to experimental results. Results show that dissociation energy outperforms other descriptors, in particular to describe ligand effects over a large electronic effect range as seen by confronting the results to the pyrR pKa values. Further insights into the Au-NpyrR bond are obtained through an energy decomposition analysis (EDA) study, which confirms the isolobal character of Au+ with H+. Finally, the correlation between the lability of the pyridine ligands toward the catalytic efficiency of the complexes could be demonstrated in an intramolecular hydroarylation reaction of alkyne. The results were rationalized considering both pre-catalyst activation and catalyst reactivity. This study establishes the possibility of correlating dissociation energy, which is a gas-phase descriptor, with condensed-phase parameters such as catalysis efficiency. It therefore holds great potential for inorganic and organometallic chemistry by opening a convenient and easy way to evaluate the electronic influence of a ligand toward a metallic center.

Accurate Evaluation of Dispersion Energies at Coupled Cluster Level to Understand the Substituent Effects in Am(III) and Eu(III) Complexes.

The effect of cyclic and aromatic substituents on the complexation behavior of phosphine oxide ligands with Am(III) and Eu(III) was investigated at density functional theory (DFT) and domain-based local pair natural orbital coupled-cluster (DLPNO-CC) levels. Combining DFT with accurate coupled cluster methods, we have evaluated the dispersion energy contributions to the complexation energies for trivalent Am and Eu complexes for the first time. Irrespective of the nature of substituents on the P atom, the electronic structure of the P═O group remains identical in all of the ligands. The study reveals the importance of dispersion interactions during complexation and is estimated to be more significant for Am(III) than for Eu(III) complexes.

Exploring the Accuracy Limits of PNO-Based Local Coupled-Cluster Calculations for Transition-Metal Complexes.

While the domain-based local pair natural orbital coupled-cluster method with singles, doubles, and perturbative triples (DLPNO-CCSD(T)) has proven instrumental for computing energies and properties of large and complex systems accurately, calculations on first-row transition metals with a complex electronic structure remain challenging. In this work, we identify and address the two main error sources that influence the DLPNO-CCSD(T) accuracy in this context, namely, (i) correlation effects from the 3s and 3p semicore orbitals and (ii) dynamic correlation-induced orbital relaxation (DCIOR) effects that are not described by the local MP2 guess. We present a computational strategy that allows us to completely eliminate the DLPNO error associated with semicore correlation effects, while increasing, at the same time, the efficiency of the method. As regards the DCIOR effects, we introduce a diagnostic for estimating the deviation between DLPNO-CCSD(T) and canonical CCSD(T) for systems with significant orbital relaxation.

Orbital pair selection for relative energies in the domain-based local pair natural orbital coupled-cluster method

For the accurate computation of relative energies, domain-based local pair natural orbital coupled-cluster [DLPNO-CCSD(T0)] has become increasingly popular. Even though DLPNO-CCSD(T0) shows a formally linear scaling of the computational effort with the system size, accurate predictions of relative energies remain costly. Therefore, multi-level approaches are attractive that focus the available computational resources on a minor part of the molecular system, e.g., a reaction center, where changes in the correlation energy are expected to be the largest. We present a pair-selected multi-level DLPNO-CCSD(T0) ansatz that automatically partitions the orbital pairs according to their contribution to the overall correlation energy change in a chemical reaction. To this end, the localized orbitals are mapped between structures in the reaction; all pair energies are approximated through computationally efficient semi-canonical second-order Møller-Plesser perturbation theory, and the orbital pairs for which the pair energies change significantly are identified. This multi-level approach is significantly more robust than our previously suggested, orbital selection-based multi-level DLPNO-CCSD(T0) ansatz [M. Bensberg and J. Neugebauer, J. Chem. Phys. 155, 224102 (2021)] for reactions showing only small changes in the occupied orbitals. At the same time, it is even more efficient without added input complexity or accuracy loss compared to the full DLPNO-CCSD(T0) calculation. We demonstrate the accuracy of the multi-level approach for a total of 128 chemical reactions and potential energy curves of weakly interacting complexes from the S66x8 benchmark set.

Trifluoromethyl-stabilized 2D nitrogen clusters: a theoretical study

The stability of 2D all nitrogen clusters containing from 6 to 96 nitrogen atoms, terminated with CF3 groups, has been explored using two computational models: dispersion corrected B3LYP functional and scaled opposite spin Møller-Plesset perturbation theory (SOS-MP2). Single point domain-based local pair natural orbital coupled-cluster theory calculations (DLPNO-CCSD(T)) was used for further energy refinement. All systems were found to be minima, and their stability increases with CF3/N ratio. Larger clusters and anion radicals were not dynamically stable, while some of the cation radicals were found to be minima on potential energy surface. The mechanism of cluster stabilization by CF3 groups is related with interaction of orbitals holding lone electron pairs and antibonding sigma orbitals.

Dualism of 1,2,4-oxadiazole ring in noncovalent interactions with carboxylic group

A number of cyclohexane and cyclohexene carboxylic acids bearing 1,2,4-oxadiazole substituent were prepared via condensation of amidoximes with anhydrides of corresponding dicarboxylic acids. All prepared compounds were studied via HRMS, 1H and 13C NMR. In addition, for five acids crystalline structures were obtained via X-ray diffraction analysis. Inspection of these X-ray structures revealed two type previously undescribed noncovalent interactions between oxadiazole ring and carboxylic group: O(carboxyl)···C(oxadiazole) and O(oxadiazole)···C(carboxyl).Computational investigation by a number of theoretical approaches (the quantum theory of atoms in molecules, the independent gradient model, natural bond orbital, molecular electrostatic potential, and Kohn-Sham energy decomposition analyses, as well as the domain based local pair-natural orbital coupled-cluster and atomic-dipole-moment-corrected Hirshfeld methods) demonstrated that these interactions are caused by the packing effect and have an electrostatic and dispersive nature.

Ionization Energies and Redox Potentials of Hydrated Transition Metal Ions: Evaluation of Domain-Based Local Pair Natural Orbital Coupled Cluster Approaches.

Hydrated transition metal ions are prototypical systems that can be used to model properties of transition metals in complex chemical environments. These seemingly simple systems present challenges for computational chemistry and are thus crucial in evaluations of quantum chemical methods for spin-state and redox energetics. In this work, we explore the applicability of the domain-based pair natural orbital implementation of coupled cluster (DLPNO-CC) theory to the calculation of ionization energies and redox potentials for hydrated ions of all first transition row (3d) metals in the 2+/3+ oxidation states, in connection with various solvation approaches. In terms of model definition, we investigate the construction of a minimally explicitly hydrated quantum cluster with a first and second hydration layer. We report on the convergence with respect to the coupled cluster expansion and the PNO space, as well as on the role of perturbative triple excitations. A recent implementation of the conductor-like polarizable continuum model (CPCM) for the DLPNO-CC approach is employed to determine self-consistent redox potentials at the coupled cluster level. Our results establish conditions for the convergence of DLPNO-CCSD(T) energetics and stress the absolute necessity to explicitly consider the second solvation sphere even when CPCM is used. The achievable accuracy for redox potentials of a practical DLPNO-based approach is, on average, 0.13 V. Furthermore, multilayer approaches that combine a higher-level DLPNO-CCSD(T) description of the first solvation sphere with a lower-level description of the second solvation layer are investigated. The present work establishes optimal and transferable methodological choices for employing DLPNO-based coupled cluster theory, the associated CPCM implementation, and cost-efficient multilayer derivatives of the approach for open-shell transition metal systems in complex environments.

Open-Shell Variant of the London Dispersion-Corrected Hartree-Fock Method (HFLD) for the Quantification and Analysis of Noncovalent Interaction Energies.

The London dispersion (LD)-corrected Hartree–Fock (HF) method (HFLD) is an ab initio approach for the quantification and analysis of noncovalent interactions (NCIs) in large systems that is based on the domain-based local pair natural orbital coupled-cluster (DLPNO-CC) theory. In the original HFLD paper, we discussed the implementation, accuracy, and efficiency of its closed-shell variant. Herein, an extension of this method to open-shell molecular systems is presented. Its accuracy is tested on challenging benchmark sets for NCIs, using CCSD(T) energies at the estimated complete basis set limit as reference. The HFLD scheme was found to be as accurate as the best-performing dispersion-corrected exchange-correlation functionals, while being nonempirical and equally efficient. In addition, it can be combined with the well-established local energy decomposition (LED) for the analysis of NCIs, thus yielding additional physical insights.

Chromone-methanol clusters in the electronic ground and lowest triplet state: a delicate interplay of non-covalent interactions.

Chromone offers two energetically almost equivalent docking sites for alcohol molecules, in which the hydroxyl group is hydrogen bonded to one of the free electron pairs of the carbonyl O atom. Here, the delicate balance between these two competing arrangements is studied by combining IR/R2PI and UV/IR/UV spectroscopy in a molecular beam supported by quantum-chemical calculations. Most interestingly, chromone undergoes an efficient intersystem crossing into the triplet manifold upon electronic excitation, so that the studies on aromatic molecule-solvent complexes are for the first time extended to such a cluster in a triplet state. As the lowest triplet state (T1) is of ground state character, powerful energy decomposition approaches such as symmetry-adapted perturbation theory (SAPT) and local energy decomposition using the domain-based local pair natural orbital coupled-cluster method (DLPNO-CCSD(T)/LED) are applied. From the theoretical analysis we infer for the T1 state a loss of planarity (puckering) of the 4-pyrone ring of the chromone unit, which considerably affects the interplay between different types of non-covalent interactions at the two possible binding sites.

Direct orbital selection within the domain-based local pair natural orbital coupled-cluster method.

Domain-based local pair natural orbital coupled cluster (DLPNO-CC) has become increasingly popular to calculate relative energies (e.g., reaction energies and reaction barriers). It can be applied within a multi-level DLPNO-CC-in-DLPNO-CC ansatz to reduce the computational cost and focus the available computational resources on a specific subset of the occupied orbitals. We demonstrate how this multi-level DLPNO-CC ansatz can be combined with our direct orbital selection (DOS) approach [M. Bensberg and J. Neugebauer, J. Chem. Phys. 150, 214106 (2019)] to automatically select orbital sets for any multi-level calculation. We find that the parameters for the DOS procedure can be chosen conservatively such that they are transferable between reactions. The resulting automatic multi-level DLPNO-CC method requires no user input and is extremely robust and accurate. The computational cost is easily reduced by a factor of 3 without sacrificing accuracy. We demonstrate the accuracy of the method for a total of 61 reactions containing up to 174 atoms and use it to predict the relative stability of conformers of a Ru-based catalyst.

Computational Protocol to Calculate the Phosphorescence Energy of Pt(II) Complexes: Is the Lowest Triplet Excited State Always Involved in Emission? A Comprehensive Benchmark Study.

The reliable calculation of phosphorescence energies of phosphor materials is at the core of designing efficient phosphorescent organic light-emitting diodes (PhOLEDs). Therefore, it is of paramount importance to have a robust computational protocol to perform those calculations in a black-box manner. In this work, we use Domain-Based Local Pair Natural Orbital Coupled Cluster theory with single, double, and perturbative triple excitation (DLPNO-CCSD(T)) calculations to attain the phosphorescence energies of a large pool of Pt(II) complexes. Several approaches to incorporate relativistic effects in our calculations were tested. In addition, we have used the DLPNO-CCSD(T) values (i.e., our best theoretical values) to assess the performance of different flavors of density functional theory including pure, hybrid, meta-hybrid, and range-separated functionals. Among the tested functionals, the M06HF functional provides the best values compared with the DLPNO-CCSD(T) ones, with a mean absolute deviation (MAD) value of 0.14 eV. In its turn, and thanks to the increased accuracy achieved in the calculation of phosphorescence energies, we also demonstrate that not all of the investigated complexes emit from their lowest-lying triplet state (T1). The outlier complexes include different complex photophysical scenarios and both Kasha and anti-Kasha types of complexes. Finally, we provide a general computational protocol to pre-screen whether T1 is actually the emissive state and to accurately calculate the phosphorescence energies of Pt(II) complexes.

A DLPNO-CCSD(T) benchmarking study of intermolecular interactions of ionic liquids.

The accuracy of correlation energy recovered by coupled cluster single-, double-, and perturbative triple-excitations, CCSD(T), has led to the method being considered the gold standard of computational chemistry. The application of CCSD(T) has been limited to medium-sized molecular systems due to its steep scaling with molecular size. The recent development of alternative domain-based local pair natural orbital coupled-cluster method, DLPNO-CCSD(T), has significantly broadened the range of chemical systems to which CCSD(T) level calculations can be applied. Condensed systems such as ionic liquids (ILs) have a large contribution from London dispersion forces of up to 150 kJ mol-1 in large-scale clusters. Ionic liquids show appreciable charge transfer effects that result in the increased valence orbital delocalization over the entire ionic network, raising the question whether the application of methods based on localized orbitals is reliable for these semi-Coulombic materials. Here the performance of DLPNO-CCSD(T) is validated for the prediction of correlation interaction energies of two data sets incorporating single-ion pairs of protic and aprotic ILs. DLPNO-CCSD(T) produced results within chemical accuracy with tight parameter settings and a non-iterative treatment of triple excitations. To achieve spectroscopic accuracy of 1 kJ mol-1 , especially for hydrogen-bonded ILs and those containing halides, the DLPNO settings had to be increased by two orders of magnitude and include the iterative treatment of triple excitations, resulting in a 2.5-fold increase in computational cost. Two new sets of parameters are put forward to produce the performance of DLPNO-CCSD(T) within chemical and spectroscopic accuracy.

The Role of Spike Protein Mutations in the Infectious Power of SARS-COV-2 Variants: A Molecular Interaction Perspective.

Specific S477N, N501Y, K417N, K417T, E484K mutations in the receptor binding domain (RBD) of the spike protein in the wild type SARS‐COV‐2 virus have resulted, among others, in the following variants: B.1.160 (20A or EU2, first reported in continental Europe), B1.1.7 (α or 20I501Y.V1, first reported in the United Kingdom), B.1.351 (β or 20H/501Y.V2, first reported in South Africa), B.1.1.28.1 (γ or P.1 or 20J/501Y.V3, first reported in Brazil), and B.1.1.28.2 (ζ, or P.2 or 20B/S484K, also first reported in Brazil). From the analysis of a set of bonding descriptors firmly rooted in the formalism of quantum mechanics, including Natural Bond Orbitals (NBO), Quantum Theory of Atoms In Molecules (QTAIM) and highly correlated energies within the Domain Based Local Pair Natural Orbital Coupled Cluster Method (DLPNO‐CCSD(T)), and from a set of computed electronic spectral patterns with environmental effects, we show that the new variants improve their ability to recognize available sites to either hydrogen bond or to form salt bridges with residues in the ACE2 receptor of the host cells. This results in significantly improved initial virus⋅⋅⋅cell molecular recognition and attachment at the microscopic level, which trigger the infectious cycle.

Mechanistic Insights into the Oxygen Atom Transfer Reactions by Nonheme Manganese Complex: A Computational Case Study on the Comparative Oxidative Ability of Manganese-Hydroperoxo vs High-Valent MnIV═O and MnIV–OH Intermediates

Understanding the comparative oxidative abilities of high-valent metal-oxo/hydroxo/hydroperoxo species holds the key to robust biomimic catalysts that perform desired organic transformations with very high selectivity and efficiency. The comparative oxidative abilities of popular high-valent iron-oxo and manganese-oxo species are often counterintuitive, for example, oxygen atom transfer (OAT) reaction by [(Me2EBC)MnIV-OOH]3+, [(Me2EBC)MnIV-OH]3+, and [(Me2EBC)MnIV═O]2+ (Me2EBC = 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) shows extremely high reactivity for MnIV-OOH species and no reactivity for MnIV-OH and MnIV═O species toward alkyl/aromatic sulfides. Using a combination of density functional theory (DFT) and ab initio domain-based local pair natural orbital coupled-cluster with single, double, and perturbative triples excitation (DLPNO-CCSD(T)) and complete-active space self-consistent field/N-electron valence perturbation theory second order (CASSCF/NEVPT2) calculations, here, we have explored the electronic structures and sulfoxidation mechanism of these species. Our calculations unveil that MnIV-OOH reacts through distal oxygen atom with the substrate via electron transfer (ET) mechanism with a very small kinetic barrier (16.5 kJ/mol), placing this species at the top among the best-known catalysts for such transformations. The MnIV-OH and MnIV═O species have a much larger barrier. The mechanism has also been found to switch from ET in the former to concerted in the latter, rendering both unreactive under the tested experimental conditions. Intrinsic differences in the electronic structures, such as the presence and absence of the multiconfigurational character coupled with the steric effects, are responsible for such variations observed. This comparative oxidative ability that runs contrary to the popular iron-oxo/hydroperoxo reactivity will have larger mechanistic implications in understanding the reactivity of biomimic catalysts and the underlying mechanisms in PSII.

Influence of halogens on organometallic open pentadienyl lanthanum complexes XLa(C5H7)2 (X = H, F–I)

The electron and structural understanding of metal-coordinated pentadienyl ligands is essential for their subsequent use in different areas of chemistry, especially in the area of organometallic chemistry. Thus, in this work we have analyzed in gas-phase the influence of group 17 elements in complexes formed with the lanthanum atom and the open pentadienyl ligand, XLa(C5H7)2, where X = H, F, Cl, Br, and I. The results, using density functional theory (PBE0/def2-TZVP) and NBO analysis, suggest that all carbon atoms of both ligands are η5 coordinated to the lanthanum atom, and X atoms play a very important role in affecting the electron transfer from the ligands to the central atom due to their electronegativity. In addition, the NBO analysis and the geometry of each structure suggest that the atoms that contribute the most as charge donors to the lanthanum atom are those at the center of the pentadienyl ligand. Energies were computed with the domain based local pair-natural orbital coupled-cluster (DLPNO-CCSD(T)) method.

Accurate Computation of the Absorption Spectrum of Chlorophyll a with Pair Natural Orbital Coupled Cluster Methods.

The ability to accurately compute low-energy excited states of chlorophylls is critically important for understanding the vital roles they play in light harvesting, energy transfer, and photosynthetic charge separation. The challenge for quantum chemical methods arises both from the intrinsic complexity of the electronic structure problem and, in the case of biological models, from the need to account for protein–pigment interactions. In this work, we report electronic structure calculations of unprecedented accuracy for the low-energy excited states in the Q and B bands of chlorophyll a. This is achieved by using the newly developed domain-based local pair natural orbital (DLPNO) implementation of the similarity transformed equation of motion coupled cluster theory with single and double excitations (STEOM-CCSD) in combination with sufficiently large and flexible basis sets. The results of our DLPNO–STEOM-CCSD calculations are compared with more approximate approaches. The results demonstrate that, in contrast to time-dependent density functional theory, the DLPNO–STEOM-CCSD method provides a balanced performance for both absorption bands. In addition to vertical excitation energies, we have calculated the vibronic spectrum for the Q and B bands through a combination of DLPNO–STEOM-CCSD and ground-state density functional theory frequency calculations. These results serve as a basis for comparison with gas-phase experiments.

Assessing the validity of DLPNO-CCSD(T) in the calculation of activation and reaction energies of ubiquitous enzymatic reactions.

The domain-based local pair natural orbital coupled-cluster with single, double, and perturbative triples excitation (DLPNO-CCSD(T)) method was employed to portray the activation and reaction energies of four ubiquitous enzymatic reactions, and its performance was confronted to CCSD(T)/complete basis set (CBS) to assess its accuracy and robustness in this specific field. The DLPNO-CCSD(T) results were also confronted to those of a set of density functionals (DFs) to understand the benefit of implementing this technique in enzymatic quantum mechanics/molecular mechanics (QM/MM) calculations as a second QM component, which is often treated with DF theory (DFT). On average, the DLPNO-CCSD(T)/aug-cc-pVTZ results were 0.51 kcal·mol-1 apart from the canonic CCSD(T)/CBS, without noticeable biases toward any of the reactions under study. All DFs fell short to the DLPNO-CCSD(T), both in terms of accuracy and robustness, which suggests that this method is advantageous to characterize enzymatic reactions and that its use in QM/MM calculations, either alone or in conjugation with DFT, in a two-region QM layer (DLPNO-CCSD(T):DFT), should enhance the quality and faithfulness of the results.

Divergence of Many-Body Perturbation Theory for Noncovalent Interactions of Large Molecules.

Prompted by recent reports of large errors in noncovalent interaction (NI) energies obtained from many-body perturbation theory (MBPT), we compare the performance of second-order Mo̷ller-Plesset MBPT (MP2), spin-scaled MP2, dispersion-corrected semilocal density functional approximations (DFAs), and post-Kohn-Sham random phase approximation (RPA) for predicting binding energies of supramolecular complexes contained in the S66, L7, and S30L benchmarks. All binding energies are extrapolated to the basis set limit, corrected for basis set superposition errors, and compared to reference results of the domain-based local pair-natural orbital coupled-cluster (DLPNO-CCSD(T)) or better quality. Our results confirm that MP2 severely overestimates binding energies of large complexes, producing relative errors of over 100% for several benchmark compounds. RPA relative errors consistently range between 5 and 10%, significantly less than reported previously using smaller basis sets, whereas spin-scaled MP2 methods show limitations similar to MP2, albeit less pronounced, and empirically dispersion-corrected DFAs perform almost as well as RPA. Regression analysis reveals a systematic increase of relative MP2 binding energy errors with the system size at a rate of approximately 0.1% per valence electron, whereas the RPA and dispersion-corrected DFA relative errors are virtually independent of the system size. These observations are corroborated by a comparison of computed rotational constants of organic molecules to gas-phase spectroscopy data contained in the ROT34 benchmark. To analyze these results, an asymptotic adiabatic connection symmetry-adapted perturbation theory (AC-SAPT) is developed, which uses monomers at full coupling, whose ground-state density is constrained to the ground-state density of the complex. Using the fluctuation-dissipation theorem, we obtain a nonperturbative "screened second-order" expression for the dispersion energy in terms of monomer quantities, which is exact for non-overlapping subsystems and free of induction terms; a first-order RPA-like approximation to the Hartree, exchange, and correlation kernel recovers the macroscopic Lifshitz limit. The AC-SAPT expansion of the interaction energy is obtained from Taylor expansion of the coupling strength integrand. Explicit expressions for the convergence radius of the AC-SAPT series are derived within RPA and MBPT and numerically evaluated. While the AC-SAPT expansion is always convergent for nondegenerate monomers when RPA is used, it is found to spuriously diverge for second-order MBPT, except for the smallest and least polarizable monomers. The divergence of the AC-SAPT series for MBPT is numerically confirmed within RPA; prior numerical results on the convergence of the SAPT expansion for MBPT methods are revisited and support this conclusion once sufficiently high orders are included. The cause of the failure of MBPT methods for NIs of large systems is missing or incomplete "electrodynamic" screening of the Coulomb interaction due to induced particle-hole pairs between electrons in different monomers, leaving the effective interaction too strong for AC-SAPT to converge. Hence, MBPT cannot be considered reliable for quantitative predictions of NIs, even in moderately polarizable molecules with a few tens of atoms. The failure to accurately account for electrodynamic polarization makes MBPT qualitatively unsuitable for applications such as NIs of nanostructures, macromolecules, and soft materials; more robust nonperturbative approaches such as RPA or coupled cluster methods should be used instead whenever possible.