Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

Density Functional Theory in the Age of Chemical Intelligence

Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Computational and Theoretical Chemistry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 22413

Share This Special Issue

Special Issue Editors

Dr. Mihai V. Putz

E-Mail Website
Guest Editor

1. Laboratory of Structural and Computational Physical-Chemistry for Nanosciences and QSAR, Biology-Chemistry Department, West University of Timisoara, Str. Pestalozzi 16, 300115 Timisoara, Romania
2. Laboratory of Renewable Energies-Photovoltaics, R&D National Institute for Electrochemistry and Condensed Matter–INCEMC–Timisoara, Str. Dr. Aurel Podeanu 144, 300569 Timișoara, Romania
Interests: quantum physical chemistry; nanochemistry; reactivity indices and principles; electronegativity; density functional theory; path integrals; enzyme kinetics; QSAR; epistemology and philosophy of science
Special Issues, Collections and Topics in MDPI journals

Dr. Ottorino Ori

E-Mail Website
Guest Editor

1. Actinium Chemical Research Institute, Via Casilina 1626/A, 00133 Rome, Italy
2. Laboratory of Renewable Energies-Photovoltaics, R&D National Institute for Electrochemistry and Condensed Matter, Dr. A. Paunescu Podeanu Str. No. 144, RO-300569 Timisoara, Romania
Interests: nanostructures; topology; topological modeling
Special Issues, Collections and Topics in MDPI journals

Dr. Savas Kaya

E-Mail Website
Guest Editor

Faculty of Science, Department of Chemistry, Cumhuriyet University, Sivas, Turkey
Interests: computational and theoretical chemistry; CDFT and its applications; electronic structure principles; chemical reactivity; solid state chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Density functional theory (DFT), as recognized by the Nobel Prize in Chemistry in 1998, is approaching new horizons of multi-, trans-, and nano-chemistry in 2021. Since its inception and follow-up innovative developments, it has succeeded in describing, the otherwise truly complex/complicated realm of many electrons evolving in many charge potential fields—including themselves, almost the entire chemistry of single and pair electronic interactions through appropriate rearrangements of potential/forces in many-electronic samples to properly represent the entire system’s structure and reactivity. However, beyond the (perhaps unique) way of representing N-interactions by 1- and 2- electronic interactions (+ the required corrections of representation, viz. exchange, correlation, gradient/perturbative terms, multiple-configurations, etc.) it was recognized, relatively recently, that such an approach opens the gate to chemical-based artificial intelligence by employing mono- and paired- bits/qubits of information in a complex information sample. Therefore, DFT is at the edge of reinventing itself either in fundamental or applicative parts: from the asymmetric Hubbard dimer to self-assembly of carbon-based supramolecular complexes, from dynamical chemical bonding/covalent bonding description to deep learning (molecular) machines/algorithms, from mean-field density matrix decompositions to time-dependent description of two-dimensional semiconductors, from conceptual DFT explaining chemical reactivity to drug-likeness, bioactive scores and anticancer peptides, and so on. All of these developments open new horizons of DFT as a theory, a versatile computational framework, and an adaptive paradigm to a plethora of phenomena in which the molecule unite with cells’ constituents and ultimately with intelligence (as an autonomous network entity of dynamical information): i.e., the molecular artificial in Cerebro and in silico models, simulations and intelligence to be next synthesized by in-vitro and in-vivo protocols during 2021. I thus kindly invite you to contribute a visionary project from your particular viewpoint, projected or sustained or aided by DFT.

Prof. Dr. Mihai V. Putz
Dr. Ottorino Ori
Dr. Savas Kaya
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

quantum chemistry and quantum computation
chemical computation and network analysis
inorganic/organic nano compounds and systems
supramolecular chemistry
chemical bond, structure, and reactivity
QSPR, QSAR, and bio-specific interactions
learning molecular machines
artificial/quantum intelligence

Related Special Issue

Density Functional Theory in the Age of Chemical Intelligence II in Molecules (1 article)

Published Papers (9 papers)

Download All Papers

Research

Jump to: Review

12 pages, 2064 KiB

Open AccessArticle

Talarolide A and Talaropeptides A–D: Potential Marine-Derived Therapeutic Peptides with Interesting Chemistry and Biological Activity Studied through Density Functional Theory (DFT) and Conceptual DFT

by Norma Flores-Holguín, Joan S. Salas-Leiva and Daniel Glossman-Mitnik

Molecules 2023, 28(18), 6708; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28186708 - 20 Sep 2023

Viewed by 738

Abstract

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A–D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A–D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The molecular geometry optimizations and frequency calculations were conducted using the Density Functional Tight Binding (DFTBA) method. This was followed by a subsequent round of geometry optimization, frequency analysis, and computation of electronic properties and chemical reactivity descriptors. We employed the MN12SX/Def2TZVP/H2O model chemistry, utilizing the Gaussian 16 program and the SMD solvation model. The analysis of the global reactivity descriptors arising from CDFT was achieved as well as the graphical comparison of the dual descriptor DD revealing the areas of the molecules with more propensity to suffer a nucleophilic or electrophilic attack. Additionally, Molinspiration and SwissTargetPrediction were considered for the calculation of molecular characteristics and predicted biological targets. These include enzymes, nuclear receptors, kinase inhibitors, GPCR ligands, and ion channel modulators. The graphical results show that Talarolide A and the Talaropeptides A–D are likely to behave as protease inhibitors. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Graphical abstract

20 pages, 9570 KiB

Open AccessArticle

Density Functional Theory Calculations and Molecular Docking Analyses of Flavonoids for Their Possible Application against the Acetylcholinesterase and Triose-Phosphate Isomerase Proteins of Rhipicephalus microplus

by Nosheen Malak, Bader S. Alotaibi, Afshan Khan, Adil Khan, Shakir Ullah, Nasreen Nasreen, Sadaf Niaz and Chien-Chin Chen

Molecules 2023, 28(8), 3606; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28083606 - 20 Apr 2023

Viewed by 1761

Abstract

Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids’ inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-β-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-β-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-β-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

17 pages, 14774 KiB

Open AccessArticle

Structural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics Simulations

by Sepideh Soltani, Shahin Sowlati-Hashjin, Conrard Giresse Tetsassi Feugmo and Mikko Karttunen

Molecules 2022, 27(23), 8417; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27238417 - 01 Dec 2022

Viewed by 1632

Abstract

Eumelanin is an important pigment, for example, in skin, hair, eyes, and the inner ear. It is a highly heterogeneous polymer with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) building blocks, of which DHICA is reported as the more abundant in natural eumelanin. The DHICA-eumelanin protomolecule consists of three building blocks, indole-2-carboxylic acid-5,6-quinone (ICAQ), DHICA and pyrrole-2,3,5-tricarboxylic acid (PTCA). Here, we focus on the self-assembly of DHICA-eumelanin using multi-microsecond molecular dynamics (MD) simulations at various concentrations in aqueous solutions. The molecule was first parameterized using density functional theory (DFT) calculations. Three types of systems were studied: (1) uncharged DHICA-eumelanin, (2) charged DHICA-eumelanin corresponding to physiological pH, and (3) a binary mixture of both of the above protomolecules. In the case of uncharged DHICA-eumelanin, spontaneous aggregation occurred and water molecules were present inside the aggregates. In the systems corresponding to physiological pH, all the carboxyl groups are negatively charged and the DHICA-eumelanin model has a net charge of

- 4

. The effect of K

^{+}

ions as counterions was investigated. The results show high probability of binding to the deprotonated oxygens of the carboxylate anions in the PTCA moiety. Furthermore, the K

^{+}

counterions increased the solubility of DHICA-eumelanin in its charged form. A possible explanation is that the charged protomolecules favor binding to the K

^{+}

ions rather than aggregating and binding to other protomolecules. The binary mixtures show aggregation of uncharged DHICA-eumelanins; unlike the charged systems with no aggregation, a few charged DHICA-eumelanins are present on the surface of the uncharged aggregation, binding to the K

^{+}

ions. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

18 pages, 5192 KiB

Open AccessArticle

Synthesis, Characterization, Thermal Analysis, DFT, and Cytotoxicity of Palladium Complexes with Nitrogen-Donor Ligands

by Sattar R. Majeed, Mina A. Amin, Fawzy A. Attaby, Marta E. Alberto and Ahmed A. Soliman

Molecules 2022, 27(3), 964; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030964 - 31 Jan 2022

Cited by 3 | Viewed by 2347

Abstract

Three new palladium complexes ([Pd(DABA)Cl₂], [Pd(CPDA)Cl₂], and [Pd(HZPY)Cl₂]) bearing dinitrogen ligands (DABA: 3,4-diaminobenzoic acid; CPDA: 4-chloro–o-phenylenediamine; HZPY: 2-hydraziniopyridine) were synthesized, characterized, and tested against breast cancer (MCF-7), prostate carcinoma cell line (PC3) and liver carcinoma cell line (HEPG2). [Pd(DABA)Cl₂] complex exhibited the highest inhibition percentage, lying between 68–71%. The hydrolysis mechanism of each palladium complex, the key step preceding the binding to the biological target, as well as their photophysical properties were explored by means of DFT and TDDFT computations. Results indicate a faster hydrolysis process for the Pd(DABA)Cl₂ complex. The computed activation energies for the first and second hydrolysis processes suggest that all the compounds could reach DNA in their monohydrated form. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

19 pages, 5278 KiB

Open AccessArticle

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

by Nitesh Kumawat, Andrejs Tucs, Soumen Bera, Gennady N. Chuev, Marat Valiev, Marina V. Fedotova, Sergey E. Kruchinin, Koji Tsuda, Adnan Sljoka and Amit Chakraborty

Molecules 2022, 27(3), 799; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030799 - 26 Jan 2022

Cited by 7 | Viewed by 4415

Abstract

The entry of the SARS-CoV-2, a causative agent of COVID-19, into human host cells is mediated by the SARS-CoV-2 spike (S) glycoprotein, which critically depends on the formation of complexes involving the spike protein receptor-binding domain (RBD) and the human cellular membrane receptor angiotensin-converting enzyme 2 (hACE2). Using classical site density functional theory (SDFT) and structural bioinformatics methods, we investigate binding and conformational properties of these complexes and study the overlooked role of water-mediated interactions. Analysis of the three-dimensional reference interaction site model (3DRISM) of SDFT indicates that water mediated interactions in the form of additional water bridges strongly increases the binding between SARS-CoV-2 spike protein and hACE2 compared to SARS-CoV-1-hACE2 complex. By analyzing structures of SARS-CoV-2 and SARS-CoV-1, we find that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) has expanded in size, indicating large conformational change relative to SARS-CoV-1 S protein. Protomer with the up-conformational form of RBD, which binds with hACE2, exhibits stronger intermolecular interactions at the RBD-ACE2 interface, with differential distributions and the inclusion of specific H-bonds in the CoV-2 complex. Further interface analysis has shown that interfacial water promotes and stabilizes the formation of CoV-2/hACE2 complex. This interaction causes a significant structural rigidification of the spike protein, favoring proteolytic processing of the S protein for the fusion of the viral and cellular membrane. Moreover, conformational dynamics simulations of RBD motions in SARS-CoV-2 and SARS-CoV-1 point to the role in modification of the RBD dynamics and their impact on infectivity. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

18 pages, 3029 KiB

Open AccessArticle

New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation

by Ali Oubella, Abdoullah Bimoussa, Abdellah N’ait Oussidi, Mourad Fawzi, Aziz Auhmani, Hamid Morjani, Abdelkhalek Riahi, M’hamed Esseffar, Carol Parish and Moulay Youssef Ait Itto

Molecules 2022, 27(3), 769; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030769 - 25 Jan 2022

Cited by 14 | Viewed by 2455

Abstract

Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide–alkyne cycloaddition reaction using CuSO₄,5H₂O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a–h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC₅₀ values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC₅₀ value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

17 pages, 2160 KiB

Open AccessArticle

DFT, ADMET and Molecular Docking Investigations for the Antimicrobial Activity of 6,6′-Diamino-1,1′,3,3′-tetramethyl-5,5′-(4-chlorobenzylidene)bis[pyrimidine-2,4(1H,3H)-dione]

by Nesreen T. El-Shamy, Ahmed M. Alkaoud, Rageh K. Hussein, Moez A. Ibrahim, Abdulrahman G. Alhamzani and Mortaga M. Abou-Krisha

Molecules 2022, 27(3), 620; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030620 - 18 Jan 2022

Cited by 28 | Viewed by 2975

Abstract

Heterocyclic compounds, including pyrimidine derivatives, exhibit a broad variety of biological and pharmacological activities. In this paper, a previously synthesized novel pyrimidine molecule is proposed, and its pharmaceutical properties are investigated. Computational techniques such as the density functional theory, ADMET evaluation, and molecular docking were applied to elucidate the chemical nature, drug likeness and antibacterial function of molecule. The viewpoint of quantum chemical computations revealed that the molecule was relatively stable and has a high electrophilic nature. The contour maps of HOMO-LUMO and molecular electrostatic potential were analyzed to illustrate the charge density distributions that could be associated with the biological activity. Natural bond orbital (NBO) analysis revealed details about the interaction between donor and acceptor within the bond. Drug likeness and ADMET analysis showed that the molecule possesses the agents of safety and the effective combination therapy as pharmaceutical drug. The antimicrobial activity was investigated using molecular docking. The investigated molecule demonstrated a high affinity for binding within the active sites of antibacterial and antimalarial proteins. The high affinity of the antibacterial protein was proved by its low binding energy (−7.97 kcal/mol) and a low inhibition constant value (1.43 µM). The formation of four conventional hydrogen bonds in ligand–protein interactions confirmed the high stability of the resulting complexes. When compared to known standard drugs, the studied molecule displayed a remarkable antimalarial activity, as indicated by higher binding affinity (B.E. −5.86 kcal/mol & Ki = 50.23 M). The pre-selected molecule could be presented as a promising drug candidate for the development of novel antimicrobial agents. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

18 pages, 8899 KiB

Open AccessArticle

The Density Functional Theory Account of Interplaying Long-Range Exchange and Dispersion Effects in Supramolecular Assemblies of Aromatic Hydrocarbons with Spin

by Ana Maria Toader, Maria Cristina Buta, Alice Mischie, Mihai V. Putz and Fanica Cimpoesu

Molecules 2022, 27(1), 45; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27010045 - 22 Dec 2021

Cited by 3 | Viewed by 2481

Abstract

Aromatic hydrocarbons with fused benzene rings and regular triangular shapes, called n-triangulenes according to the number of rings on one edge, form groundstates with n-1 unpaired spins because of topological reasons. Here, we focus on methodological aspects emerging from the density functional theory (DFT) treatments of dimer models of the n = 2 triangulene (called also phenalenyl), observing that it poses interesting new problems to the issue of long-range corrections. Namely, the interaction comprises simultaneous spincoupling and van der Waals effects, i.e., a technical conjuncture not considered explicitly in the benchmarks calibrating long-range corrections for the DFT account of supramolecular systems. The academic side of considering dimer models for calculations and related analysis is well mirrored in experimental aspects, and synthetic literature revealed many compounds consisting of stacked phenalenyl cores, with intriguing properties, assignable to their long-range spin coupling. Thus, one may speculate that a thorough study assessing the performance of state-of-the-art DFT procedures has relevance for potential applications in spintronics based on organic compounds. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

Review

Jump to: Research

15 pages, 521 KiB

Open AccessReview

Atoms-In-Molecules’ Faces of Chemical Hardness by Conceptual Density Functional Theory

by Savas Kaya and Mihai V. Putz

Molecules 2022, 27(24), 8825; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27248825 - 12 Dec 2022

Cited by 7 | Viewed by 1693

Abstract

The chemical hardness concept and its realization within the conceptual density functional theory is approached with innovative perspectives, such as the electronegativity and hardness equalization of atoms in molecules connected with the softness kernel, in order to examine the structure–reactivity equalization ansatz between the electronic sharing index and the charge transfer either in the additive or geometrical mean picture of bonding. On the other hand, the maximum hardness principle presents a relation with the chemical stability of the hardness concept. In light of the inverse relation between hardness and polarizability, the minimum polarizability principle has been proposed. Additionally, this review includes important applications of the chemical hardness concept to solid-state chemistry. The mentioned applications support the validity of the electronic structure principles regarding chemical hardness and polarizability in solid-state chemistry. Full article

(This article belongs to the Special Issue Density Functional Theory in the Age of Chemical Intelligence)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Density Functional Theory in the Age of Chemical Intelligence

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Related Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI