Formation Of Molecular Complexes Research Articles

EFFECT OF THE H2O-EtOH AND H2O-DMSO SOLVENTS ON THE γ-CYCLODEXTRIN SOLVATION

Cyclodextrins are cyclic molecules that consist of D-glucopyranose units connected by α-1,4 glycoside bonds. Cyclodextrins are already used in the composition of drugs to increase the solubility of active substances and are ever more in demand in technologies for the development of new hybrid materials for various industrial processes. A structural feature of cyclodextrins is the presence of a hydrophobic cavity capable of including hydrophobic molecules with the formation of molecular complexes both in solution and in the solid phase. Thermodynamic parameters of cyclodextrin solvation are necessary for the scientific selection of the solvent and prediction of the reactivity of cyclodextrins for carrying out processes with the greatest efficiency. In this regard, in this work, distribution coefficients of γ-cyclodextrin were determined by the method of distribution of the substance between two immiscible phases with a water-dimethyl sulfoxide (water-ethanol) solvent of variable composition and n-hexane and the changes in the Gibbs energy of re-solvation were calculated. The distribution coefficient of γ-CD in mixed solvents is higher than in water. The change in the Gibbs energy during the transfer of γ-CD from water to its mixture with dimethyl sulfoxide and ethanol indicates a weakening of the macrocycle solvation. A comparative analysis of the effect of H2O-EtOH and H2O-DMSO solvents on changes in the solvated state of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, and γ-cyclodextrin was carried out. It was assumed that the changes in the solvated state of cyclodextrins have a major effect on the stability of molecular complexes of cyclodextrins with flavonoids rutin and quercetin in aqueous-ethanol media.

HYDROGEN BOND IN POTENTIALLY MESOGENIC MOLECULAR COMPLEXES OF 4-(PHENYLAZO)BENZOIC ACID AND 4-(PHENYLAZO)PHENOL WITH PYRIDINE DERIVATIVES

Using experimental and theoretical methods, it has been shown that hydrogen-bonded molecular complexes in two-component systems based on 4-pyridyl-4'-n-alkyloxybenzoates (n = 7, 12) with 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol (composition of 1:1) are formed. Quantum chemistry methods (DFT (B3LYP)/cc-pVTZ) were used to determine the conformational properties of 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol molecules. It has been shown that the introduction of 4-carboxy and 4-hydroxy groups into the azobenzene molecule has practically no effect on the energy characteristics of the trans-cis isomerization process. The energy, geometric, and electronic characteristics of intermolecular hydrogen bonds in the H-complexes have been estimated. The calculations showed that the H-complexes of 4-pyridyl-4-n-propyloxybenzoate with 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol differ significantly from each other in geometric structure: the complex with 4-(phenylazo)benzoic acid – rod-shaped, complex with 4-(phenylazo)phenol – angular. A comparison of the energy characteristics of H-complexes, as well as the characteristics of hydrogen bonds, showed that a stronger hydrogen bond is formed in the complex with 4-(phenylazo)benzoic acid than in the complex with 4-(phenylazo)phenol. The results of modeling dimers of molecules of 4-(phenylazo)benzoic acid, 4-(phenylazo)phenol, reproducing intermolecular interactions in crystals, and their hydrogen-bonded complexes allow to conclude that in the process of self-organization of systems with a composition of 1:1, associates of 4-(phenylazo)benzoic acid molecules, associates of 4-(phenylazo)phenol molecules will be broken and H-complexes with 4-pyridyl-4'-alkyloxybenzoates will be formed instead. Changes in the experimental IR spectra recorded for the initial components and for systems with a composition of 1:1 confirm the formation of molecular complexes. The structural units of the studied systems based on 4-pyridyl-4'-alkyloxybenzoates with 4-(phenylazo)benzoic acid and 4-(phenylazo)phenol with a composition of 1:1 can be considered supramolecules, formed by hydrogen bonding. The structure of supermolecules and the presence of their geometric anisotropy indicate their potential mesogenicity. The sample of H-complexes of 4-(phenylazo)phenol and 4-pyridyl-4'-n-dodecyloxybenzoate (composition of 1:1) was studied for the manifestation of mesomorphic properties using the method of polarization thermomicroscopy. The textures registered in a polarizing microscope allow to conclude that the H-complex has a smectic mesophase in the temperature range of 101.4–109.4 °C.

Single molecule mass photometry reveals the dynamic oligomerization of human and plant peroxiredoxins

SummaryProtein oligomerization is central to biological function and regulation, yet its experimental quantification and measurement of dynamic transitions in solution remain challenging. Here, we show that single molecule mass photometry quantifies affinity and polydispersity of heterogeneous protein complexes in solution. We demonstrate these capabilities by studying the functionally relevant oligomeric equilibria of 2-cysteine peroxiredoxins (2CPs). Comparison of the polydispersity of plant and human 2CPs as a function of concentration and redox state revealed features conserved among all 2CPs. In addition, we also find species-specific differences in oligomeric transitions, the occurrence of intermediates and the formation of high molecular weight complexes, which are associated with chaperone activity or act as a storage pool for more efficient dimers outlining the functional differentiation of human 2CPs. Our results point to a diversified functionality of oligomerization for 2CPs and illustrate the power of mass photometry for characterizing heterogeneous oligomeric protein distributions in near native conditions.

An Imaging Platform for Evaluating Complex Formation in Real Time Applied to Translation Initiation in Living Cells

Elucidating the formation of molecular complexes in living cells is key for understanding cellular homeostasis, but has not been amenable to quantitative microscopy. Here we established a platform for real-time quantification of molecular interactions to monitor the formation of complexes that results in a differential diffusion from their components. We have applied this to one of the most dynamic processes: the regulation of mRNA translation. We observe that diffusion of initiation factors (IFs) changes markedly upon their association with mRNA. Quantifying their binding dynamics revealed the sequence of IFs assembly and disassembly in cell lines and the clustering of translation in neurons. This methodology revealed translation regulation at unprecedented spatial and temporal resolution and can be applied to the formation of any endogenous complex that results in a measurable shift in diffusion.

Complexation of Cyclodextrins with Benzoic Acid in Water-Organic Solvents: A Solvation-Thermodynamic Approach.

The aim of this research is to obtain new data about the complexation between β-cyclodextrin (β-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. This research may help developing cyclodextrin-based pharmaceutical formulations through the choice of the appropriate solvent mixture that may be employed in the industrial application aiming to control the reactions/processes in liquid phase. In this paper, NMR results for the molecular complex formation between BA and β-CD ([BA⊂β-CD]) in D2O-DMSO-d6 and in D2O-EtOH have shown that the stability of the complex in the H2O-DMSO-d6 varies within the experimental error, while decreases in H2O-EtOH. Changes in the Gibbs energy of BA resolvation in water and water–dimethylsulfoxide mixtures have been obtained and have been used in the analysis of the reagent solvation contributions into the Gibbs energy changes of the [BA⊂β-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between β-CD and BA as well as the structure of the [BA⊂β-CD] complex and the energy of β-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA⊂β-CD] complex in H2O-EtOH and H2O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA⊂β-CD] molecular complexation as well as the reagent solvation contributions in H2O-EtOH and H2O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.

Design and Optimization of a Self-Assembling Complex Based on Microencapsulated Calcium Alginate and Glutathione (CAG) Using Response Surface Methodology.

The aim of this work was to characterize and optimize the formation of molecular complexes produced by the association of calcium alginate and reduced glutathione (GSH). The influence of varying concentrations of calcium and GSH on the production of microcapsules was analyzed using response surface methodology (RSM). The microcapsules were characterized by thermogravimetric analysis (TGA-DTG) and infrared spectroscopy (FTIR) in order to assess the hydration of the complexes, their thermal stability, and the presence of GSH within the complexes. The optimum conditions proposed by RSM to reach the maximum concentration of GSH within complexes were a 15% w/v of GSH and 1.25% w/v of CaCl2, with which a theorical concentration of 0.043 mg GSH per mg of CAG complex was reached.

STUDY OF THE MOLECULAR STRUCTURE OF VALINE BY QUANTUMCHEMICAL CALCULATIONS

In this paper, calculations were performed in an isolated system using ab initio and Density Functional Theory (DFT) approaches to investigate the mechanism of molecular complex formation in valine, an amino acid. Calculations have represented that the valine molecule has intramolecular hydrogen bonds and that intermolecular hydrogen bonds are used to generate dimer and trimer complexes. The Raman spectral line (?? (OH) = 3749 cm−1 ) corresponding to the O-H vibration of the valine molecule shifted to a lower frequency of 343.9 cm-1 at the O-H bond in the trimer complex and 1533.2 cm-1 at the O-H bond due to intermolecular hydrogen bonding

Abstract P-20: Sub 3 Resolution Cryo-EM Structure of Eukaryotic Small (40S) Ribosomal Subunit

Background: The ribosome is a molecular machine that translates mRNAs into proteins. In eukaryotes, ribosome consists of small (40S) and large (60S) subunits. Translation in eukaryotes is a complicated molecular process that involves the formation of various molecular complexes consisting of ribosomal subunits and protein factors. Cryo-EM approaches such as single particle analysis are widely used for structural analysis of components and intermediates of the translation machinery. However, the process of translation in plants is still poorly characterized at a structural level. Here, we present the structure of Triticum aestium small ribosomal subunit obtained at sub 3 resolution that can be used for further structural studies of the translation process in plants. Methods: The structures of the 40S subunits purified from wheat germ extract were obtained using high-resolution single particle cryo-EM. For cryo-EM sample preparation were used Quantifoil R 1.2/1.3 grids coated with an additional 2 nm amorphous carbon film were glow-discharged for 30 seconds at 15 mA using PELCO easiGlow (Ted Pella). 3 µL of the sample were applied onto the grids, blotted for 3 sec at 10°C and 100% humidity, and plunge-frozen in liquid ethane using Vitrobot Mark IV (Thermo Fisher). Cryo-EM data were collected using a Cs-corrected Titan Krios (Thermo Fisher) transmission electron microscope, equipped with a Falcon II direct electron detector. Data were acquired with defocus range of -0.6 to -2.0 at a nominal magnification of 75,000x, giving a calibrated pixel size of 0.86 Å/pixel. The micrographs were recorded as movie stacks. The exposure time for each stack was 1.6 s, corresponding to a total electron dose of ~84 e-/Å2 fractionated into 32 frames (~2.6 e-/Å2 per single frame). A total of 5521 movie stacks was collected. Raw cryo-EM data preprocessing was performed with Warp software (Tegunov et al., 2019). All further data processing steps were performed using the cryoSPARC v3.2.0 software (Punjani et al., 2017). Results: For final cryo-EM map refinement, 140,000 particles were used resulting in 2.7 Å resolution estimated using an FSC=0.143 gold-standard threshold. The obtained structural data clearly demonstrate the peculiarities of the spatial organization of the 40S ribosomal subunit, like the motility of the head relative to the body revealed by 3D variability analysis. Conclusion: The resulting structure was solved at a significantly higher resolution compared to the previously published structure of a plant ribosome (Armache et al., 2010) and will be used as a reference for further studies of translation initiation in plants.

Quantifying Frustrations for Molecular Complexes with Noncovalent Interactions.

Molecular systems bound together through noncovalent interactions are involved in a lot of life-essential processes such as molecular recognition, signal transduction, and allosteric regulation. While cooperation as an important effect discovered in these systems focuses on the behavior of system's entirety, we need also examine the behavior of individual parts. In this work, using the distortion energy as the descriptor, we quantify frustration as the energetic loss of individual parts due to the formation of nonadditive molecular complexes. The applicability of our approach has been illustrated by a few simple clusters. Our results show that the frustration effect is smaller than the cooperation effect, but same as cooperativity, it can be both positive and negative. The ultimate benefit of a system made of multiple parts is dictated by the balance between the cooperative behavior among parts and the sacrifice from its individuals. This conflicting yet complementary conceptual pair of cooperation and frustration provides us with a different perspective from the systems' viewpoint for molecular complexes. This new angle of appreciating molecular complexes can be applied in conformational changes, enzymatic catalysis, and many more.

Formation of Noncovalent Complexes between Complex Mixtures of Polycyclic Aromatic Hydrocarbons (Asphaltenes) and Substituted Aromatics Studied by Fluorescence Spectroscopy

Quantification of the formation of molecular complexes between simple organic aromatic molecules is straightforward for pure components of definite composition; however, it becomes challenging when...

Linear Multiselenium Interactions in Dicationic Oligomers of 1,5-(Diselena)canes: Behavior of Semc σ(mc c-ne e) (6≤mc ≤16) Elucidated with QTAIM Dual Functional Analysis.

The intrinsic dynamic and static nature m c center‐n e electron interactions of the σ‐type σ(m cc‐n ee) were elucidated for the Se‐Se interactions in dicationic oligomers of Se(CH2CH2CH2)2Se (1 (Se, Se)) [n 2+ (Se, Se): n=1–8], especially for m c≥6, where n 2+ (Se, Se: n=1–8) are abbreviated by n 2+ (n=1–8), respectively. QTAIM dual functional analysis (QTAIM‐DFA) was applied to the interactions. Perturbed structures generated using coordinates derived from the compliance constants (Cii) were employed for QTAIM‐DFA. Each Se‐*‐Se in 1 2+ and 2 2+ has the nature of CT‐TBP (trigonal bipyramidal adduct formation through CT) and Cov‐w (weak covalent), respectively, which supply the starting points of the investigations. The asterisk emphasizes the existence of a bond critical point on the interaction. All Se‐*‐Se in 3 2+ are classified by the regular closed shell (r‐CS) interactions and characterized as CT‐MC (molecular complex formation through CT), which are denoted as r‐CS/CT‐MC, except for the central interaction, of which nature is r‐CS/CT‐TBP. Most interactions in 4 2+–8 2+ are r‐CS/t‐HBwc (typical‐HB with covalency) but some are pure‐CS/t‐HBnc (t‐HB with no covalency). The linear Se2n 2+ interactions in 2 2+–8 2+ seem close to those without any limitations, since the nature of Se‐*‐Se inside and outside of (CH2CH2CH2)2 are very similar with each other. The linear Se2n 2+ interactions in 3 2+–8 2+ are shown to be analyzed as σ(mcc‐nee: 6≤mc≤16), not by the accumulated σ(3c–4e).

Modification of polysulfide electrolyte by applying various amines, thiourea and urea as efficient additives to improve photovoltaic performance of quantum dot-sensitized solar cells

In this study, for the first time we reported a low-cost and straightforward method to modify the polysulfide electrolyte using amine additives including aromatic amines (1,8-naphthalenediamine, 1,5-naphthalenediamine), linear amines (ethylenediamine, diethylamine, ethylamine, tert-butylamine, and butylamine), thiourea, and urea in the polysulfide electrolyte system to improve the CdS/CdSe QDSSCs performance. The photovoltaic data showed that the highest power conversion efficiencies (PCEs) were obtained for 1,5-naphthalenediamine amongst aromatic amine groups, diethylamine amidst linear amine groups and thiourea. The best-measured PCE was 3.42% (JSC = 18.98 mA·cm−2, VOC = 0.50 V, FF = 0.36) at AM1.5, which was due to presence of thiourea additive in the polysulfide electrolyte. The results of data revealed that the interaction between thiourea additive, TiO2, and redox couple in the electrolyte solution caused to a molecular complex formation, increase the electron lifetime (τ), JSC and, ultimately, improve the PCE value compared to other additives under investigation in this study.

Preparation and characterization of native starch-ibuprofen molecular inclusion complexes

Starch is a biodegradable and biocompatible polymer recognized as a versatile starting material for developing innovative drug delivery systems. In this way, the present research work investigates the ability of bamboo and corn starches to carrier ibuprofen via the formation of molecular inclusion complexes by the Acidification of an Alkaline Solution and the Heating-Sealing methods. The water ratio and the reaction time used in each procedure influence the yield and efficiency of complexation; thus, the yield varies between 16.3% and 89.6% for the bamboo starch and between 30.3% and 74.5% for the corn starch. The complexing efficiencies reach values up to 10.30% ± 0.02% when bamboo starch was used and up to 22.35% ± 0.04% for corn starch. The thermal characteristics and the pH-dependent drug release pattern exhibited by the obtained complexes keep a closer relationship with their semicrystalline structures. On this basis, starch complexes arise as promising alternatives to deliver active molecules at the intestinal level and offer attractive possibilities for generating added value to native starch sources like bamboo.

Comparison of non-covalent binding interactions between three whey proteins and chlorogenic acid: Spectroscopic analysis and molecular docking

Non-covalent binding interactions between three whey proteins β-lactoglobulin (β-Lg), α-lactalbumin (α-La) and bovine serum albumin (BSA) with chlorogenic acid (CA) were investigated using spectroscopic analysis and molecular docking. Fluorescence study showed that CA quenched the fluorescence of three whey proteins through static mode. The binding number was equal to 1 for three proteins and binding affinity in declined order was: α-La > β-Lg > BSA. Thermodynamic parameters revealed contribution of hydrophobic force in three systems. Fluorescence resonance energy transfer (FRET) measurements indicated that energy transfer occurs between three proteins and CA in probability of α-La > BSA > β-Lg. Variation in surface charge indicated the involvement of electrostatic interaction. Surface hydrophobicity (H0) were declined with decrease degree of α-La > β-Lg > BSA. α-La and β-Lg were unfolded with more flexible structure while BSA skeleton was more compact after interacting with CA. Modeling study revealed that the most likely binding sites for the three proteins were outer surface, cleft and subdomain I for β-Lg, α-La and BSA respectively. Docking results also suggested the contribution of hydrophobic interaction and hydrogen bond (β-Lg, α-La) for formation of molecular nano complexes between whey proteins and CA.

Structural chemistry of host – guest molecular architectures based on mercury-containing macrocycles

Metallomacrocycles that include several metal ions with the Lewis acid properties are peculiar antipodes of crown ethers (referred to as ‘anticrowns’ in the literature). Recently these architectures have been extensively investigated when searching for efficient and selective anion receptors. In this review, we analyze the data on the molecular and crystal structures of supramolecular complexes of mercury-containing macrocycles (hosts) with anions or neutral nucleophiles (guests). The emphasis is on the identification and systematization of the structure types of complexes in dependence of the guest molecule nature, as well as the macrocycle composition and structure. The factors affecting the selectivity of coordination and competitive ability of various electron donor moieties of guest molecules to binding to the macrocycle are considered. The data in the literature on the nonvalent host – guest and host – host interactions, which are responsible for the formation of molecular complexes and their supramolecular association in crystals, are analyzed. The formulated structural regularities of these coordination compounds with an unusual type of molecular architecture open ways to design directly promising molecular materials on their basis.The bibliography includes 161 references.

Quantitative single-protein imaging reveals molecular complex formation of integrin, talin, and kindlin during cell adhesion

Single-molecule localization microscopy (SMLM) enabling the investigation of individual proteins on molecular scales has revolutionized how biological processes are analysed in cells. However, a major limitation of imaging techniques reaching single-protein resolution is the incomplete and often unknown labeling and detection efficiency of the utilized molecular probes. As a result, fundamental processes such as complex formation of distinct molecular species cannot be reliably quantified. Here, we establish a super-resolution microscopy framework, called quantitative single-molecule colocalization analysis (qSMCL), which permits the identification of absolute molecular quantities and thus the investigation of molecular-scale processes inside cells. The method combines multiplexed single-protein resolution imaging, automated cluster detection, in silico data simulation procedures, and widely applicable experimental controls to determine absolute fractions and spatial coordinates of interacting species on a true molecular level, even in highly crowded subcellular structures. The first application of this framework allowed the identification of a long-sought ternary adhesion complex—consisting of talin, kindlin and active β1-integrin—that specifically forms in cell-matrix adhesion sites. Together, the experiments demonstrate that qSMCL allows an absolute quantification of multiplexed SMLM data and thus should be useful for investigating molecular mechanisms underlying numerous processes in cells.

Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1

Tripartite motif (TRIM)7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1 (GN1), the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis and, thus, represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal TRIM and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C terminus. To contribute to the understanding of the mechanism of action of TRIM7, we solved the X-ray crystal structure of its B30.2 domain (TRIM7B30.2) in two crystal forms at resolutions of 1.6 Å and 1.8 Å. TRIM7B30.2 exhibits the typical B30.2 domain fold, consisting of two antiparallel β-sheets of seven and six strands, arranged as a distorted β-sandwich. Furthermore, two long loops partially cover the concave face of the β-sandwich defined by the β-sheet of six strands, thus forming a positively charged cavity. We used sequence conservation and mutational analyses to provide evidence of a putative binding interface for GN1. These studies showed that Leu423, Ser499, and Cys501 of TRIM7B30.2 and the C-terminal 33 amino acids of GN1 are critical for this binding interaction. Molecular dynamics simulations also revealed that hydrogen bond and hydrophobic interactions play a major role in the stability of a modeled TRIM7B30.2-GN1 C-terminal peptide complex. These data provide useful information that could be used to target this interaction for the development of potential therapeutic agents.

Exploring chemical reactions in a quantum degenerate gas of polar molecules via complex formation

A recent experiment reported for the first time the preparation of a Fermi degenerate gas of polar molecules and observed a suppression of their chemical reaction rate compared to the one expected from a purely classical treatment. While it was hypothesized that the suppression in the ultracold regime had its roots in the Fermi statistics of the molecules, this argument is inconsistent with the fact that the Fermi pressure should set a lower bound for the chemical reaction rate. Therefore it can not be explained from standard two-body $p$-wave inelastic collisions. Here we develop a simple model of chemical reactions that occur via the formation and decay of molecular complexes. We indeed find that pure two-body molecule losses are unable to explain the observed suppression. Instead we extend our description beyond two-body physics by including effective complex-molecule interactions possible emerging from many-body and effective medium effects at finite densities and in the presence of trapping light. %Under this framework we observe that additional complex-molecule collisions, which manifest as a net three-body molecular interaction could give rise to the additional suppression. Although our effective model is able to quantitatively reproduce recent experimental observations, a detailed understanding of the actual physical mechanism responsible for these higher-order interaction processes is still pending.

HIV-2 Vif and foamy virus Bet antagonize APOBEC3B by different mechanisms

The family of human APOBEC3 (A3) restriction factors is formed by seven different proteins, A3A–D and A3F–H. Among these A3s, A3B harbors strong restriction activity against several retroviruses, such as SIV, and MLV. How lentiviruses and other retroviruses, prevalent in many primate species, counteract A3B is poorly understood.In this study, we found that A3B strongly inhibited SIVmac and HIV-2 infectivity, which was antagonized by their Vif proteins. Both SIVmac and HIV-2 Vifs diminished the protein level of A3B in viral producer cells, and hindered A3B incorporation into viral particles. We observed that HIV-2 Vif binds A3B and induces its degradation by assembly of an A3-Vif-CUL5-ElonginB/C E3-ligase complex. A3B and HIV-2 Vif localize and interact in the nucleus.In addition, we also found that the accessory protein Bet of prototype foamy virus (PFV) significantly antagonized the anti-SIVmac activity of A3B. Like Vif, Bet prevented the incorporation of A3B into viral particles. However, in contrast to Vif Bet did not induce the degradation of A3B. Rather, Bet binds A3B to block formation of high molecular weight A3B complexes and induces A3B cytoplasmic trapping.In summary, these findings indicate that A3B is recognized by diverse retroviruses and counteracted by virus-specific pathways that could be targeted to inhibit A3B mutating activity in cancers.

Density functional modeling of Am3+/Eu3+ selectivity with diethylenetriaminepentaacetic acid and its bisamide chelates.

ABSTRACT Density-functional theory calculations were applied to molecular structure and complex formation reaction modelings of metal ion complexes with diethylenetriaminepentaacetic acid (DTPA) and its bisamide (DTPABA) chelates to understand the metal ion selectivity between Am3+ and Eu3+. The calculated complexes with DTPA and DTPABA chelates reproduced the coordination geometries of experimental crystal structures. Calculated Gibbs free energies of the complex formation reactions indicated that Am3+ ion forms higher stable complexes with both chelates than Eu3+ ion, being consistent with the experimental results. The higher Am3+ selectivity over Eu3+ was suggested to originate in the larger bond overlap between Am3+ 5 f-orbital and N 2s, 2p-orbital. This means that the covalent contribution between the metal ion and donor atoms differentiates the complex formation stabilities, leading to the Am3+/Eu3+ selectivity. We expect that this study contributes to systematize the origin of metal ion selectivity and to accelerate novel ligand exploration.