Energy Decomposition Analysis Research Articles

Computational study of core modified dipyriamethyrin for the competitive complexation of Am3+/Cm3+ from their trichlorides.

In the process of handling and storage of radioactive actinides it is essential to selectively sequester the minor actinides, such as Am and Cm, through a competitive complexation process. Herein we computationally designed two core modified ligands (L21- and L3) through systematic oxygen substitution at the NH sites of dipyriamethyrin (L1_2H), a hexadentate expanded porphyrin, and studied their competitive complexation towards trivalent actinides (An = Am/Cm) from their trichlorides using density functional theory (DFT). We observed shorter An-N bonds and longer An-O bonds in complexes based on core modified ligands (L21- and L3). The An-Cl bond length increases with increasing axial coordination number (i.e., from L12- to L3) to accommodate the ligands. All the bonds were identified to be electrostatic in nature. L12- exhibits shorter bonds and larger bond orders on complexing with Am than with Cm. On moving from complexes of L21- to L3, the An-N bond lengths are shortened, while An-O bond lengths become larger. Between the complexes of Am and Cm, there is marginal difference in their bond distances with L21- and L3. Charge analysis shows ligand to metal charge transfer during coordination, with back-donation from An to N/O and Cl. The calculated spin-density analysis indicates that An remains in its trivalent oxidation state on complexation, while orbital occupation analysis shows that the 5f and 6d orbitals are involved in bonding; this was confirmed by molecular orbital (MO) analysis that shows the complexes of L21- and L3 to exhibit higher degeneracy in their overlapping MOs. Further, the energy decomposition analysis (EDA) confirms that all ionic bonds are primarily due to electrostatic contributions, where the orbital contributions increase from L12- to L3 complexes and maximum covalency was observed in Cm complexes due to the energy matching between the 5f orbitals of Cm and the 2p orbitals of N and Cl, compared to Am. To confirm the competitiveness in the complexation of the ligand towards Am vs. Cm, the thermodynamic parameters were analysed for the ligand and metal substitution reactions. L12- shows more affinity towards Am than Cm, while L21- and L3 prefer Cm.

In silico modelling of chelate stabilized tetrylene derivatives.

The steric and electronic effects of specific ligands can play crucial roles in stabilizing unsaturated tetrylene species. In this work, hybrid density functional theory (DFT) methods, quantum theory of atoms in molecules (QTAIM) investigations and natural bond orbital (NBO) calculations are employed to evaluate the stabilization of low-valent E(ii) centers (E = Si, Ge, Sn, Pb) through the chelating effect generated by an electron-rich ligand containing the P[double bond, length as m-dash]C-P[double bond, length as m-dash]X moiety (X = O or S). Based on several types of analyses, such as the bond dissociation energy (BDE) or the interplay between attractive (i.e., charge-transfer) and repulsive (i.e., Pauli-exchange) effects, we highlight that the stabilization energy induced by chelation is up to ca. 70 kcal mol-1 for silylenes, yet slightly decreases within the heavier analogues. Moreover, it is emphasized that chelate-stabilized silylenes can form highly stable hybrid metal-metalloid complexes with transition metals (e.g., gold). Due to push-pull effects occurring in the X→Si(ii)→Au fragment, the Si(ii)→Au bonding is significantly stronger than the X→Au, P(sp2)→Au or π(C[double bond, length as m-dash]P)→Au donor-acceptor bonds, which are potentially formed by the electron-rich P[double bond, length as m-dash]C-P[double bond, length as m-dash]X unit with the AuCl fragment. These findings are supported by energy decomposition analysis (EDA) calculations.

Exploring the mechanism of action of spirooxindoles as a class of CDK2 inhibitors: a structure-based computational approach.

Cyclin-dependent kinase 2 (CDK2) regulates cell cycle checkpoints in the synthesis and mitosis phases and plays a pivotal role in cancerous cell proliferation. The activation of CDK2, influenced by various protein signaling pathways, initiates the phosphorylation process. Due to its crucial role in carcinogenesis, CDK2 is a druggable hotspot target to suppress cancer cell proliferation. In this context, several studies have identified spirooxindoles as an effective class of CDK2 inhibitors. In the present study, three spirooxindoles (SOI1, SOI2, and SOI3) were studied to understand their inhibitory mechanism against CDK2 through a structure-based approach. Molecular docking and molecular dynamics (MD) simulations were performed to explore their interactions with CDK2 at the molecular level. The calculated binding free energy for the spirooxindole-based CDK2 inhibitors aligned well with experimental results regarding CDK2 inhibition. Energy decomposition (ED) analysis identified key binding residues, including I10, G11, T14, R36, F82, K89, L134, P155, T158, Y159, and T160, in the CDK2 active site and T-loop phosphorylation. Molecular mechanics (MM) energy was identified as the primary contributor to stabilizing inhibitor binding in the CDK2 protein structure. Furthermore, the analysis of binding affinity revealed that the inhibitor SOI1 binds more strongly to CDK2 compared to the other inhibitors under investigation. It demonstrated a robust interaction with the crucial residue T160 in the T-loop phosphorylation site, responsible for kinase activation. These insights into the inhibitory mechanism are anticipated to contribute to the development of potential CDK2 inhibitors using the spirooxindole scaffold.

Structure, stability, reactivity and bonding in noble gas compounds.

Noble gases (Ngs) are recognized as the least reactive elements due to their fully filled valence electronic configuration. Their reluctance to engage in chemical bond formation necessitates extreme conditions such as low temperatures, high pressures, and reagents with high reactivity. In this Perspective, we discuss our endeavours in the theoretical prediction of viable Ng complexes, emphasizing the pursuit of synthesizing them under nearly ambient conditions. Our research encompasses various bonding categories of Ng complexes and our primary aim is to comprehend the bonding mechanisms within these complexes, utilizing state-of-the-art theoretical tools such as natural bond orbital, energy decomposition, and electron density analyses. These complex types manifest distinct bonding scenarios. In the non-insertion type, the donor-acceptor interaction strength hinges on the polarizing ability of the binding atom, drawing the electron density of the Ng towards itself. In certain instances, especially with heavier Ng elements, this interaction reaches a magnitude where it can be considered a covalent bond. Conversely, in most insertion cases, the Ng prefers to share electrons to form a covalent bond on one side while interacting electrostatically on the other side. In rare cases, both bonds may be portrayed as electron-shared covalent bonds. Furthermore, a host cage serves as an excellent platform to explore the limits of achieving Ng-Ng bonds (even for helium), under high pressure.

Boiling, critical, and freezing temperatures in light of molecular descriptors: correlation and causation.

In the pursuit of tracking some physicochemical properties of fluids down to the molecular level, ab initio molecular surface analyses were performed on 169 molecules. This included electrostatic potential (EP), average local ionization energy (ALIE), and electron localization function (ELF) mapped onto an electron density isosurface value of 0.001 au. Using stepwise linear regression (SLR) analysis, it was found that besides the well-studied EP, ALIE and ELF played important roles in determining the normal boiling and freezing points and critical temperatures of fluids. Apparently, the ALIE and ELF were relevant to the attractive polarization forces and repulsive Pauli forces, respectively, between molecules. To further demonstrate and rationalize this assumption, a localized molecular orbital energy decomposition analysis (LMO-EDA) was carried out. In the LMO-EDA analysis, the complexes of the helium atom, He, and ClCl, ClBr, ClI, OCO, OCS, OCSe, and CO/OC molecules were investigated, where the helium atom faced different molecular sites in each molecule. Fortunately, the results showed that lower the ALIE value on a molecular site, the stronger (i.e., more attractive) the polarization interaction energy. The results also indicated that higher the ELF value on a molecular site, the stronger (i.e., more repulsive) the Pauli interaction. The work is aimed to present novel molecular-based rationales to physical chemists, chemical engineers, and materials scientists.

Planar tetracoordinate beryllium compounds with a partially covalent Be-Ng bond.

An analysis of the thermodynamic and kinetic stability and the nature of the chemical bond in hypercoordinated compounds with the formula BeH3Ng+ (Ng = He-Rn) through high-level calculations is presented in this work. Thermochemical calculations show that, for the heavier noble gases (Ar-Rn), these systems are thermodynamically stable at room temperature; however, this stability decreases due to a weakening of the Be-H2 interaction, while the Be-Ng bond strengthens going down the periodic table. These results are complemented by Born Oppenheimer molecular dynamics simulations, in which the increasing tendency to dissociate the Be-H2 bond is evidenced. The nature of the chemical bonding depends on the analysis performed. On the one hand, the interacting quantum atoms method indicates that the covalent contribution is around 25 to 30%. On the other hand, the electron density topology indicates a covalent nature for compounds with Kr-Rn, while Hirshfeld population analysis in conjunction with Mayer's bond order establishes polar covalent behavior. The geometrical parameters and natural energy decomposition analysis (NEDA) indicate a covalent nature, allowing us to consider that the Be-Ng bond has a partially covalent character.

Interactions of phosphate, phosphine oxide and phosphoramide ligands with Th(IV)

The complexation behavior of phosphate, phosphine oxide, and phosphoramide ligands with Th(IV) is investigated at the Density Functional Theory (DFT) level. Employing Energy Decomposition Analysis (EDA), the study reveals significant contributions of geometric strain and dispersion interactions in determining the stability of these complexes. It is observed that the orbital interaction in the various Th(IV) complexes increases in the order phosphate < phosphine oxide < phosphoramide.

Theoretical investigation of tautomerism of 2- and 4-pyridones: origin, substituent and solvent effects.

Computational investigation at the BHandHLYP/6-311+G(d,p) level of theory of the gas-phase tautomerism of 2- and 4-pyridones confirmed the slight prevalence of lactim in the case of the former, but its dominance in the case of the latter, as shown previously. Examination of aromaticity by using HOMA, EDDB, NBOdel, NICS and AICD led to the conclusion that tautomerization of 4-pyridone results in greater aromaticity gain. It is also driven by the Pauli repulsion relief, which was revealed by the tautomerization energy decomposition analysis. By contrast, in the case of 2-pyridone, lactim is favoured by orbital and electrostatic interactions and disfavoured by the Pauli repulsion. Aromaticity gain in this case is smaller. The position of the tautomeric equilibrium can be modulated by substituent inductive effects (Cl and F), inductive and resonance effects (NH2 and NO2), hydrogen bonding (NO2), and medium polarity, the increase of which increases lactam population.

Interactions and reactivity in crystalline intermediates of mechanochemical cyclorhodation reactions.

There is experimental evidence that solid mixtures of the rhodium dimer [Cp*RhCl2]2 and benzo[h] quinoline (BHQ) produce two different polymorphic molecular cocrystals called 4α and 4β under ball milling conditions. The addition of NaOAc to the mixture leads to the formation of the rhodacycle [Cp*Rh-(BHQ)Cl], where the central Rh atom retains its tetracoordinate character. Isolate 4β reacts with NaOAc leading to the same rhodacycle while isolate 4α does not under the same conditions. We show that the puzzling difference in reactivity between the two cocrystals can be traced back to fundamental aspects of the intermolecular interactions between the BHQ and [Cp*RhCl2]2 fragments in the crystalline environment. To support this view, we report a number of descriptors of the nature and strength of chemical bonds and intermolecular interactions in the extended solids and in a cluster model. We calculate formal quantum mechanical descriptors based on electronic structure, electron density, and binding and interaction energies including an energy decomposition analysis. Without exception, all descriptors point to 4β being a transient structure higher in energy than 4α with larger local and global electrophilic and nucleophilic powers, a more favorable spatial and energetic distribution of the frontier orbitals, and a more fragile crystal structure.

Exploring the electronic and steric effects on the dimerization of intramolecular frustrated Lewis pairs: a comparison between aminoboranes and aminoalanes.

The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory. We systematically varied the substituents to gradually increase their bulkiness, including H, CH3, t-Bu, Ph, and Mes groups. Starting from the most stable conformer of the monomers, a frustrated Lewis pair or classic Lewis adduct, we studied the dimerization process for all systems, revealing significant variations in the Gibbs free energy. Dimerization was favored in four aminoboranes and six aminoalanes, depending on the specific combinations of substituents. Applying an energy decomposition analysis, we found that the preparation energy of the monomers and the non-orbital interactions between them are the primary contributors to the observed energetic differences, showing a clear linear relationship. Additionally, we analyzed the electronic effects by increasing the acidity of the Lewis acid, observing a shift toward endergonic and exergonic directions in aminoboranes and aminoalanes, respectively. This shift was attributed to the stabilization of a classic Lewis adduct. This study underscores three crucial factors influencing dimer formation: (i) substituent size, (ii) stabilization of the classic Lewis adduct conformation, and (iii) covalent radii of the Lewis centers. Understanding these factors is essential for designing FLPs and preventing unwanted dimerization that could affect their catalytic performance in H2 activation processes.

Enhancement of energy decomposition analysis in fragment molecular orbital calculations.

Energy decomposition analysis is one of the most attractive features of fragment molecular orbital (FMO) calculations from the point of view of practical applications. Here we report some enhancements for PIEDA in the ABINIT-MP program. One is a separation of the dispersion-type stabilization from the electron correlation energy, traditionally referred to as the "dispersion interaction" (DI). Another is an alternative evaluation of the electrostatic (ES) interaction using the restrained electrostatic potential (RESP) charges. The GA:CT stacked base pair and the Trp-Cage miniprotein were used as illustrative examples.

Unveiling the Anomaly of Reduction of Carborane-bis-silylene-Stabilised Silylone/Germylone Leading to Unusual Oxidation of Si0 /Ge0 to SiI /GeI with EDA-NOCV Analyses.

Researchers have successfully isolated Si0 /Ge0 species, termed silylone and germylone, with two lone pairs of electrons on them. These elusive compounds have been stabilised in singlet ground states by using different donor base ligands. Driess et al. in particular have made strides in this area, isolating carborane-bis-silylene-stabilised silylone/germylone and their N+ /Pb analogues. Carborane (C2 B10 H10 ) plays a pivotal role as a redox-active ligand, converting from closo-carborane to nido-carborane with the addition of two electrons. Notably, anomalous oxidation of Si0 /Ge0 centres in carborane-bis-silylene-stabilised species to SiI /GeI has been reported, resulting in the formation of dimeric SiI -SiI /GeI -GeI di-cationic units. The energy decomposition analysis coupled with natural orbital for chemical valence (EDA-NOCV) study focuses on the carborane-bis-silylene ligand in the free state, and its three other species, including silylone/germylone species. Interestingly, it reveals that the carborane unit in an anionic doublet state tends to form one electron-sharing bond and one dative bond with the counter fragment in its cationic doublet state. This helps us to rationalise why the carborane unit undergoes intramolecular electronic rearrangements leading to the formation of a di-anionic carborane unit with a significantly elongated C-C bond (2.38-2.68 Å) and undergoes unusual oxidation of Si0 /Ge0 to SiI /GeI .

Balance between Physical Interpretability and Energetic Predictability in Widely Used Dispersion-Corrected Density Functionals.

We assess the performance of different dispersion models for several popular density functionals across a diverse set of noncovalent systems, ranging from the benzene dimer to molecular crystals. By analyzing the interaction energies and their individual components, we demonstrate that there exists variability across different systems for empirical dispersion models, which are calibrated for reproducing the interaction energies of specific systems. Thus, parameter fitting may undermine the underlying physics, as dispersion models rely on error compensation among the different components of the interaction energy. Energy decomposition analyses reveal that, the accuracy of revPBE-D3 for some aqueous systems originates from significant compensation between dispersion and charge transfer energies. However, revPBE-D3 is less accurate in describing systems where error compensation is incomplete, such as the benzene dimer. Such cases highlight the propensity for unpredictable behavior in various dispersion-corrected density functionals across a wide range of molecular systems, akin to the behavior of force fields. On the other hand, we find that SCAN-rVV10, a targeted-dispersion approach, affords significant reductions in errors associated with the lattice energies of molecular crystals, while it has limited accuracy in reproducing structural properties. Given the ubiquitous nature of noncovalent interactions and the key role of density functional theory in computational sciences, the future development of dispersion models should prioritize the faithful description of the dispersion energy, a shift that promises greater accuracy in capturing the underlying physics across diverse molecular and extended systems.

Small molecule activation by sila/germa boryne species.

The inability of p-block elements to participate in π-backbonding restricts them from activating small molecules like CO, H2 , and so forth. However, the development of the main group metallomimetics became a new pathway, where the main-group elements like boron can bind and activate small molecules like CO and H2 . The concept of the frustrated Lewis pair, Boron-Boron multiple bonds, and borylene are previously illustrated. Some of these reported classes of boron species can mimic the jobs of the metal complexes. Hence, we have theoretically studied the binding of CO/N2 molecules at B-center of elusive species like sila/germa boryne stabilized by donor base ligands (cAAC)BE(Me)(L), where E  Si, L  cAACMe , NHCMe , PMe3 , E  Ge, L  cAACMe and (NHCMe )BE(Me)(cAACMe )). The substitutional analogues of (cAACR )BSiR1 (cAAC) and E  P, L  cAACMe ) have been studied by density functional theory (DFT), natural bond orbital, QTAIM calculations and energy decomposition analysis (EDA) coupled with natural orbital for chemical valence (NOCV) analyses. The computed bond dissociation energy and inner stability analyses by the EDA-NOCV method showed that the CO molecule can bind at the B-center of the above-mentioned species due to stronger σ-donor ability while binding of N2 has been theoretically predicted to be weak. The energy barrier for the CO binding is estimated to be 13-14 kcal/mol by transition state calculation. The change of partial triple bond character to single bond nature of the BSi bond and the bending of CBSi bond angle of sila-boryne species are the reason for the activation energy. Our study reveals the ability of such species to bind and activate the CO molecule to mimic the transition metal-containing complexes. We have additionally shown that binding of Fe(CO)4 and Ni(CO)3 is feasible at Si-center after binding of CO at the B-center.

Temperature response behavior of poly(1-vinyl-3-methylimidazole dimethyl phosphate-co-N-isopropylacrylamide) in aqueous and ester solutions driven by hydrogen bonding

A series of poly(1-vinyl-3-methylimidazole dimethyl phosphate-co-N-isopropylacrylamide) oligomers was synthesized by reversible addition-fragmentation chain transfer polymerization. The co-oligomers exhibited a pH-tunable lower critical solution temperature (LCST) phase transition in aqueous solutions. By changing the pH of the aqueous solution (HCI), the hydrogen bonding between the internal molecules of the co-oligomers and water molecules was weakened, which effectively reduced the cloud-point temperature. Poly(1-vinyl-3-methylimidazole dimethyl phosphate-co-N-isopropylacrylamide) oligomers exhibit an upper critical solution temperature (UCST) type of phase transition in an ester solution, which is associated with the formation and breaking of hydrogen bonds within the co-oligomers molecules. FT-IR analysis revealed the effect of temperature on hydrogen bonding between the functional groups. Energy decomposition, Electrostatic Potential (ESP), Atoms-in-Molecules (AIM), and Interaction region indicator (IRI) analyses demonstrated the presence of hydrogen bond donors N–H and imidazole ring C–H, and hydrogen bond acceptors C = O and P = O in the co-oligomers. The sites of hydrogen bonding between the co-oligomers and the solvent molecules as well as intermolecular forces were found to be the main factors contributing to the LCST/UCST-type phase transition.

Unraveling Reactivity Pathways: Dihydrogen Activation and Hydrogenation of Multiple Bonds by Pyramidalized Boron-Based Frustrated Lewis Pairs.

The activation of H2 by pyramidalized boron-based frustrated Lewis Pairs (FLPs) (B/E-FLP systems where "E" refers to N, P, As, Sb, and Bi) have been explored using density functional theory (DFT) based computational study. The activation pathway for the entire process is accurately characterized through the utilization of the activation strain model (ASM) of reactivity, shedding light on the underlying physical factors governing the process. The study also explores the hydrogenation process of multiple bonds with the help of B/N-FLP. The research findings demonstrate that the liberation of activated dihydrogen occurs in a synchronized, albeit noticeably asynchronous, fashion. The transformation is extensively elucidated using the activation strain model and the energy decomposition analysis. This approach suggests a co-operative double hydrogen-transfer mechanism, where the B-H hydride triggers a nucleophilic attack on the carbon atom of the multiple bonds, succeeded by the migration of the protic N-H.

Insight into the adsorption properties of CO2 and H2 gas on the B12Y12 (Y[dbnd]N, P, As, Sb) nanocages from host-guest interaction perspective

Owing to the huge increase in population and industrial activity over the past century, the natural air environment is becoming increasingly polluted. Therefore, it is essential to monitor and regulate pollution levels. Numerous research efforts have been conducted to create acceptable gas-sensitive materials for continuing monitoring and sounding alarms when dangerous chemical vapors are present at higher than intended levels. In the theoretical analysis of the adsorption properties, density functional theory calculations were utilized for B12Y12 (YN, P, As, Sb) nanocages as gas sensor towards common air pollutants, CO2 and H2 molecules. In this study, the geometrical and electronic properties, highest occupied molecular orbital (HOMO) – lowest unoccupied molecular orbital (LUMO) energy gap, frontier molecular orbital (FMO) analysis were investigated. The shortest H2 and CO2 distances after the adsorption process were for B12N12 with distances less than 2.8 Å and 2.2 Å, respectively, and the adsorption energy when CO2 was adsorbed on the B12N12 surface was less than −26 kJ/mol, indicating that adsorption occurred physically and exorthemically. The Eg of B12N12 is 5.9 eV; therefore, compared to others, this nanocage is the most stable for H2 and CO2 adsorption. In addition, a positive ∇2ρ value and negative H value from the QTAIM analysis indicated the formation of moderate interaction between B12N12 and CO2. Density of states (DOS) and natural bond orbital (NBO) studies were performed to better understand the nanocage adsorption properties, which revealed the presence of physical interactions. Energy decomposition analysis was performed to investigate the stability of gas adsorption onto a nanocage surface. The results showed that ΔEDISP and ΔEELEC were significant factors in determining the adsorption process stability, and the adsorption type was physisorption based on ΔEPOL value for all nanocages. Molecular dynamics (AIMD simulation) analysis revealed changes in the bond lengths and angles during adsorption. This work provides the first theoretical framework for the carbon monoxide and hydrogen adsorption performance of B12Sb12 and B12As12.

Binding selectivity analysis of AURKs inhibitors through molecular dynamics simulation studies.

Aurora kinases (AURKs) have been identified as promising biological targets for the treatment of cancer. In this study, molecular dynamics simulations were employed to investigate the binding selectivity of three inhibitors (HPM, MPY, and VX6) towards AURKA and AURKB by predicting their binding free energies. The results show that the inhibitors HPM, MPY, and VX6 have more favorable interactions with AURKB as compared to AURKA. The binding energy decomposition analysis revealed that four common residue pairs (L139, L83), (V147, V91), (L210, L154), and (L263, L207) showed significant binding energies with HPM, MPY, and VX6, hence responsible for the binding selectivity of AURKA and AURKB to the inhibitors. The MD trajectory analysis also revealed that the inhibitors affect the dynamic flexibility of protein structure, which is also responsible for the partial selectivity of HPM, MPY, and VX6 towards AURKA and AURKB. As expected, this study provides useful insights for the design of potential inhibitors with high selectivity for AURKA and AURKB.

Revealing the Role of Noncovalent Interactions on the Conformation of the Methyl Group in Tricyclic Orthoamide.

Tricyclic orthoamides are valuable molecules with wide-ranging applications, including organic synthesis and molecular recognition. Their structural properties make them intriguing, particularly the eclipsed all-trans conformer, which is typically less stable than the alternated conformation and is a rare phenomenon in organic chemistry. However, it gains stability in crystalline and hydrated settings, challenging the existing theoretical explanations. This study investigates which factors make eclipsed conformers more stable using experimentally reported anhydrous (ATO) and hydrated (HTO) crystal structures. Employing the quantum theory of atoms in molecules, noncovalent interaction index, and pairwise energy decomposition analysis, we delve into the noncovalent interaction environment surrounding the molecule of interest. In ATO, dispersive interactions dominate, whereas in HTO, both dispersive and electrostatic contributions are observed due to the presence of water molecules. Anchored to the lone pairs of the nitrogen atom in the orthoamide tricycle, water molecules prompt the methyl group's eclipsing through intermolecular and intramolecular interactions. This work resolves the long-standing conflict behind why tricyclic orthoamide has an eclipsed conformation by establishing the stabilization factors. These insights have implications for crystal engineering and design, enhancing our understanding of structural behavior in both crystalline and hydrated environments.

Uncovering the mechanism of selective stabilization of high-energy diastereoisomers via inclusion

Supramolecular systems may be used to stabilize otherwise unstable isomers to find alternative synthetic pathways. It has been reported that cucurbit[8]uril can stabilize trans-I and trans-II CuII\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{{\ extrm{II}}}$$\\end{document} cyclam, whereas trans-III is the only non-substituted trans CuII\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{{\ extrm{II}}}$$\\end{document} cyclam diastereoisomer found outside of the host molecule experimentally. Quantum chemistry methods can provide valuable insight into the intermolecular interactions involved in these inclusion complexes. All five possible trans diastereoisomers of CuII\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{{\ extrm{II}}}$$\\end{document} cyclam were studied within the host molecule to calculate the interaction energy and free energy of association for each complex. The relative free energies of the five free cyclams confirm that trans-I and trans-II are the most energetically accessible diastereoisomers from the initial trans-III starting point. Energy decomposition analysis was used to identify the attractive and repulsive interactions between cyclam and cucurbit[8]uril and showed that trans-II encounters repulsive forces almost three times greater than trans-I, which may explain the 7:3 ratio of trans-I to trans-II within cucurbit[8]uril that occurs experimentally. Optimized complex geometries with trans-III, IV, and V show that the cyclams protrude out of cucurbit[8]uril, whereas trans-I and trans-II become more encapsulated and elongate the host, suggesting that the position of the cyclam is extremely important when forming non-covalent interactions. Our results agree with the experimental findings and provide greater insight into why the most stable isolated cyclam diastereoisomer, trans-III, does not form a complex.