Complexation Research Articles

The effect of acceptor and donor doping on the electronic properties of the half-Heusler TiNiSn.

Optimizing the electronic transport properties of thermoelectric compounds is commonly achieved by either donor or acceptor atom doping to increase the conduction of the appropriate carrier type, electrons or holes, respectively. Enhancing carrier mobility and carrier concentration will both lead to optimized electronic properties. In this work the effect of various dopants on the electronic properties of TiNiSn was explored, by modeling the doping of an ideal compound on the Ti-sublattice with acceptor or donor elements. Using ab initio DFT calculations and a set of analytical expressions of transport properties, the temperature dependencies of the electronic properties were calculated, to examine possible n-type or p-type dopants to be used in further experimental studies.

ETS-NOCV description of chemical bonding: from covalent bonds to non-covalent interactions

ContextThe interpretation of ETS-NOCV for typical covalent and dative-covalent chemical bonds is presented and compared with that for halogen bonds. Possible tuning of the strength of halogen bonding is considered, first by applying an electric field (modeled by the point charges or the electric field vector), and then by constructing a model transition-metal complex with enhanced strength of halogen bonding. For all the systems, the ETS-NOCV picture is supplemented by the analysis of the deformation in molecular electrostatic potential (ΔMEP). The results demonstrate important characteristic features of the analysis based on NOCV: (i) this approach is based on pairs of orbitals with antibonding and bonding character and, thus, allows us to “extract” the “diatomic-like” picture of chemical bonding; (ii) the NOCV-pair contributions to the deformation density often correspond to donation (AB) and back-donation (AB) of electron density between the fragments. The results for halogen bonding demonstrate that it is possible to tune their strength by an electric field in the molecular environment; the halogen-bond energy can reach the order of magnitude typical of dative-covalent bonds. However, the nature of halogen bonds still differs from that of dative-covalent interactions, as the accumulation of electron density between fragments is of significantly lower magnitude. The main effect of the electric field is an increase in the polarization of the fragments, which is clearly manifested by the deformation in the MEP.MethodsAll calculations were performed using the ADF/AMS package. The BLYP exchange–correlation functional was employed with Grimme’s dispersion correction (D3 version) and Becke-Johnson damping, using TZP basis sets. The deformation in the MEP was determined as ΔVr=VABr-VAr-VBr, with the same fragment definition as in the ETS-NOCV method.

Valence tautomerism, non-innocence, and emergent magnetic phenomena in lanthanide-organic tessellations.

Coordination networks based on lanthanide ions entangle collective magnetic phenomena, otherwise only observed in inorganic 4f materials, and the tunable spatial and electronic structure engineering intrinsic to coordination chemistry. In this review, we discuss the use of 2D-structure-directing linear {LnII/IIII2} nodes to direct the formation of polymeric coordination networks. The equatorial coordination plasticity of {LnII/IIII2} results in broad structural diversity, including previously unobtainable tessellations containing motifs observed in quasicrystalline tilings. The new phases host also magnetic frustration, which is at the origin of enhanced magnetic refrigeration potential. Finally, careful redox matching of Ln node and frontier orbitals of the ligand scaffold has culminated in the discovery of quantitative valence tautomeric conversion in a molecule-based Ln material, opening up new avenues for combining exotic magnetic phenomena with an encoded switch.

Coordination Complexes of Cobalt with Pyrazole-Based Ligands and Potential Applications

Transition metals are one of the central aspects of modern coordination chemistry research. In addition to being well-studied, cobalt is a unique transition metal due to its presence in vitamin B12. Pyrazole-based structures are common in nature and organic synthesis. Over the past decade, our research group has focused on synthesizing and characterizing novel cobalt, nickel, and copper organometallic complexes. To date, we have reported three cobalt complexes, five nickel complexes and one copper complex with pyrazole-derived ligands. Based on the current scientific data, we are optimistic about potential applications of our coordination complexes with cobalt and pyrazole-based ligands. In this work we review applications of cobalt complexes with pyrazole-based ligands described in recent literature to explore possible applications of compounds synthesized and characterized by our research group.

Advances in the Light-Promoted Transformations of N-Heterocyclic Carbene Ligated Boryl Radicals

AbstractOrganoboron compounds are integral to modern life, with extensive applications in synthesis, materials science, medicine, and various other domains closely linked to human endeavors. NHC-BH3, noted for its stability, ease of synthesis, and high reactivity as a boryl radical precursor, has emerged as a key focus in boryl radical chemistry. Recently, the visible-light-induced single electron transfer (SET) and hydrogen atom transfer (HAT) processes have garnered considerable interest, presenting innovative strategies for generating boryl radicals from NHC-BH3. In the context of this review, our focus is on the synthesis of C–B and X–B bonds under visible light irradiation, facilitated by NHC-BH3. Furthermore, we explored the role of NHC-BH3 as a hydrogen donor or halogen atom transfer reagent in the construction of C–C bonds.1 Introduction2 Hydroboration3 Borylation4 Construction of X–B Bonds (X = N, O, S)5 Halogen Atom Transfer Reagent and Hydrogen Donor6 Conclusion

Alternative Solvents for Life: Framework for Evaluation, Current Status, and Future Research.

Life is a complex, dynamic chemical system that requires a dense fluid solvent in which to take place. A common assumption is that the most likely solvent for life is liquid water, and some researchers argue that water is the only plausible solvent. However, a persistent theme in astrobiological research postulates that other liquids might be cosmically common and could be solvents for the chemistry of life. In this article, we present a new framework for the analysis of candidate solvents for life, and we deploy this framework to review substances that have been suggested as solvent candidates. We categorize each solvent candidate through the following four criteria: occurrence, solvation, solute stability, and solvent chemical functionality. Our semiquantitative approach addresses all the requirements for a solvent not only from the point of view of its chemical properties but also from the standpoint of its biochemical function. Only the protonating solvents fulfill all the chemical requirements to be a solvent for life, and of those only water and concentrated sulfuric acid are also likely to be abundant in a rocky planetary context. Among the nonprotonating solvents, liquid CO2 stands out as a planetary solvent, and its potential as a solvent for life should be explored. We conclude with a discussion of whether it is possible for a biochemistry to change solvents as an adaptation to radical changes in a planet's environment. Our analysis provides the basis for prioritizing future experimental work to explore potential complex chemistry on other planets. Key Words: Habitability-Alternative solvents for life-Alternative biochemistry. Astrobiology xx, xxx-xxx.

Catalytic effect of the in-situ rhodium(III) complexes in surfactant medium on the auto-oxidation of 1,2-hydroxyphenylthiourea: A theoretical and experimental study for rhodium(III) sensing

1,2-hydroxyphenylthiourea(HPTU) undergoes auto-oxidation to form an yellow colored dimer. The process of auto-oxidation is enhanced by the presence of trace quantities of transition metal ions and transition metal complexes that act as catalysts. In the current study, catalytic potential of rhodium(III) complexes on the auto-oxidation of 1,2-hydroxyphenylthiourea(HPTU) was studied theoretically using quantum mechanical calculations and experiments were carried out using photometry and fluorometry. DFT studies inferred that [Rh(Py)6]Cl3 showed a better catalytic activity in the dimerization of HPTU. Theoretical studies were subsequently validated through experiments using photometric methods and the range of detection was determined to be 6 ng/mL–100 ng/mL. The detection limit was observed to be 2 ng/mL. Analytical parameters such as pH, reagent concentration, metal ion concentration, appropriate activators and surfactants were established.

An electrochemical biosensor for mercury(II) detection based on DNA-Au bio-bar codes coupled with enzymatic dual signal amplification

Mercury ion (Hg2+) is one of the most toxic heavy metal pollutants, which not only causes enormous damage and pollution to environment, but also results in numerous irreversible impairments to the human health. Herein, a novel amperometric DNA biosensor was constructed for Hg2+ detection based on DNA-Au bio-bar codes coupled with enzymatic dual signal amplification. Carboxylated graphene oxide (GO − COOH) was selected as electrode modified material to provide anchoring sites for attachment DNA oligonucleotides. Substrate DNA was attached on the GO − COOH surface via covalent coupling interaction between amine (–NH2) groups on DNA and carboxyl (–COOH) groups on GO. AuNPs co-linked with bio-bar code DNA and target DNA via Au-S bonds were utilized as DNA-Au bio-bar codes, which labeled with HRP through avidin/biotin interaction. In the presence of object Hg2+, the target DNA on HRP-labeled DNA-Au bio-bar codes (HRP-DNA-Au bio-bar codes) hybridized with substrate DNA on GO − COOH via thymine-Hg2+-thymine (T-Hg2+-T) coordination chemistry. HRP-DNA-Au bio-bar codes catalyze hydroquinone oxidation to benzoquinone in presence of by hydrogen peroxide, generating an enhanced amperometric response signal. The current signal of biosensor is proportional to the logarithm of Hg2+ concentrations ranging from 25 pM to 10 μM with a detection limit of 10 pM (S/N = 3). Furthermore, without the need for target amplification, the prepared electrochemical DNA biosensor exhibited superior selectivity against other interfering metal ions, providing a facile and sensitive platform for Hg2+ detection in real environmental samples.

Sustainable humification of food waste slurry through thermally activated persulfate oxidation

This study introduces a thermoanalytical approach utilizing sodium persulfate (PS) to expedite the humification of food waste (FW) through advanced oxidation processes (AOPs). The method harnesses heat-induced free radicals to break down complex organic compounds into simpler forms, leading to the formation of humic substances. We conducted an analysis of changes in soluble chemical oxygen demand (SCOD), dissolved organic carbon (DOC), ammonia nitrogen, soluble proteins, and sugars, employing advanced techniques such as three-dimensional fluorescence spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM). The findings indicate that the activation of PS at 70°C effectively increases SCOD and DOC levels, converts proteins into soluble forms, and enhances NH4+-N content. This study, which focuses on the utilization of thermal methods, affirms that the thermal activation of persulfate (PS) significantly boosts the humification of food waste (FW), presenting a sustainable approach for waste management and resource recovery.

Unveiling the Potential of Sulfur-Rich Macrocyclic Chelators Against Cadmium Poisoning.

Cadmium, an extremely toxic heavy metal, poses significant health risks to humans. Despite persistent research efforts, the development of effective treatments for cadmium intoxication remains a challenge. This study aims to establish the chemical groundwork for improved chelation therapy options against cadmium poisoning. Herein, the coordination chemistry of a series of sulfur-rich macrocycles featuring different polyamine backbones (NO3S, TACD3S, DO4S, TRI4S, and TE4S) was investigated. Our results demonstrate that DO4S exhibits exceptional Cd2+ scavenging ability, forming the most thermodynamically stable complex among the studied chelators. The stability of the Cd2+ complexes decreases in the following order: DO4S (pCd = 19.8) ≫ NO3S (pCd = 11.0) ∼ TRI4S (pCd = 10.9) ≫ TE4S (pCd = 7.8) > TACD3S (pCd = 7.3). DFT calculations demonstrated that the backbone polarization properties dictate the observed reduced stability when shifting from DO4S to the other ligands. DO4S showed superior affinity when compared to the state-of-the-art Cd2+ chelators such as EDTA (pCd = 16.7), DTPA (pCd = 17.4), and DMSA (pCd = 13.2). The findings from this study underscore the potential of the examined chelating agents, with particular reference to DO4S, paving the way for the development of advanced chelation therapies to combat cadmium poisoning.

Investigations on the Synthesis of Chiral Ionic-Liquid-Supported Ligands and Corresponding Transition-Metal Catalysts: Strategy and Experimental Schemes

Ionic liquids have been utilized in numerous significant applications within the field of chemistry, particularly in organic chemistry, due to their unique physical and chemical properties. In the realm of asymmetric transition-metal-catalyzed transformations, chiral ionic-liquid-supported ligands and their corresponding transition-metal complexes have facilitated these processes in unconventional solvents, especially ionic liquids and water. These innovative reaction systems enable the recycling of transition-metal catalysts while producing optically active organic molecules with comparable or even higher levels of chemo-, regio-, and stereoselectivity compared to their parent catalysts. In this short review, we aim to provide an overview of the structures of chiral ionic-liquid-supported ligands and the synthetic pathways for these ligands and catalysts. Various synthetic methodologies are demonstrated based on the conceptual frameworks of diverse chiral ionic-liquid-supported ligands. We systematically present the structures and comprehensive synthetic pathways of the chiral ionic-liquid-supported ligands and the typical corresponding transition-metal complexes that have been readily applied to asymmetric processes, categorized by their parent ligand framework. Notably, the crucial experimental procedures are delineated in exhaustive detail, with the objective of enhancing comprehension of the pivotal aspects involved in constructing chiral ionic-liquid-tagged ligands and compounds for both scholars and readers. Considering the current limitations of such ligands and catalysts, we conclude with remarks on several potential research directions for future breakthroughs in the synthesis and application of these intriguing ligands.

Alternative Uses of Fermented Wheat Bran: A Mini Review

Bran is a by-product primarily derived from the milling of grains, notably wheat and rice. It is rich in dietary fiber, vitamins, minerals, and phytochemicals yet often remains underutilized in its raw form. This raw material is abundant and readily available, offering significant potential for value-added applications. In its unprocessed state, bran boasts a complex chemical composition that includes proteins, lipids, and carbohydrates. However, it also contains antinutritional components such as phytic acid and enzyme inhibitors, which may limit its nutritional efficacy. Through further processing or storage, these components can be transformed to enhance their antioxidant properties and overall nutritional value. Bran is used in both animal feed and human food applications, though its use is often hindered by its high fiber content and antinutritional factors. To maximize its utility, innovative processing techniques are required to improve its digestibility and nutrient availability. Fermentation presents a viable method for enhancing the nutritional profile of bran. This process typically employs microorganisms such as bacteria, yeast, or fungi to break down complex compounds, thereby increasing the bioavailability of nutrients. After fermentation, bran exhibits improved chemical composition and nutritional value. The process reduces antinutritional components while enriching the bran with beneficial compounds like amino acids and probiotics. Utilizing fermented bran in animal feed offers numerous advantages, including enhanced digestive health, improved nutrient absorption, and augmented disease resistance. It serves as a sustainable feed alternative that supports livestock growth while aligning with ecological goals. The processing of bran through fermentation not only maximizes its nutritional potential but also contributes to sustainable agricultural practices by reducing waste. Future research should focus on optimizing fermentation techniques and exploring novel applications in both feed and food industries to fully realize the benefits of this versatile by-product.

Ligand Many-Body Expansion as a General Approach for Accelerating Transition Metal Complex Discovery.

Methods that accelerate the evaluation of molecular properties are essential for chemical discovery. While some degree of ligand additivity has been established for transition metal complexes, it is underutilized in asymmetric complexes, such as the square pyramidal coordination geometries highly relevant to catalysis. To develop predictive methods beyond simple additivity, we apply a many-body expansion to octahedral and square pyramidal complexes and introduce a correction based on adjacent ligands (i.e., the cis interaction model). We first test the cis interaction model on adiabatic spin-splitting energies of octahedral Fe(II) complexes, predicting DFT-calculated values of unseen binary complexes to within an average error of 1.4 kcal/mol. Uncertainty analysis reveals the optimal basis, comprising the homoleptic and mer symmetric complexes. We next show that the cis model (i.e., the cis interaction model solved for the optimal basis) infers both DFT- and CCSD(T)-calculated model catalytic reaction energies to within 1 kcal/mol on average. The cis model predicts low-symmetry complexes with reaction energies outside the range of binary complex reaction energies. We observe that trans interactions are unnecessary for most monodentate systems but can be important for some combinations of ligands, such as complexes containing a mixture of bidentate and monodentate ligands. Finally, we demonstrate that the cis model may be combined with Δ-learning to predict CCSD(T) reaction energies from exhaustively calculated DFT reaction energies and the same fraction of CCSD(T) reaction energies needed for the cis model, achieving around 30% of the error from using the CCSD(T) reaction energies in the cis model alone.

The thermal behavior of silicone-based composite materials and the assessment of the gases that result from the thermal degradation process

A series of composite materials were prepared on the basis of polydimethylsiloxane (PDMS) having different siloxane functionality, filled with two types of metal complexes containing siloxane segment, derived from condensation of 1,3-bis(3-aminopropyl)tetramethyldisiloxane with 3,5-di-tert-butyl-2-hydroxibenzaldehyde and 5-chloro-2-hydroxibenzaldehyde. The main objective of the proposed study is to introduce transition metal complexes with Schiff-base ligands that contain siloxane spacers into the PDMS matrix and examine the effect these complexes have on thermal stability. We investigated the produced gases using thermogravimetry coupled with FTIR and MS in order to analyze the thermal stability and degradation pathways of a variety of silicone composite materials.

Evaluation of the Chemotherapeutic Potential of Medicinal Plant Mespilus germanica Fruit Extract: Cell Death Pathways and DNA Damage Mechanism

Plant extracts are a mixture of natural complex compounds containing various biological activities, including anticancer properties. The fact that they have fewer side effects than synthetic drugs has made plant extracts an important strategy in cancer treatment The purpose of this study was to explore the chemotherapeutic potential of Mespilus germanica (medlar) fruit extract. The compound content of the extract was determined by HPLC. The proliferative concentration (PRO) and the concentration inhibiting the proliferation of half of the cells (IC50) were determined by the MTT viability test. PRO and IC50 concentrations were treated to A549 lung cancer cells for 48 hours. The study groups were determined as 3 groups: control, PRO, and IC50. Total mRNA was obtained from the cells by using the Trizol Reagent-chloroform method. cDNA synthesis was performed from total mRNA. mRNA gene expression levels of programmed cell death markers were detected by RT-qPCR. For all group studies, p

Съвременен атомистичен модел на изкуството. Част трета

The Contemporary Atomistic Model of Art sought represents an ontogenetic process of creation, communication and perception of the artwork in the environment that surrounds us and that is within us. Instead of immutable wholes (holism), we have infinite sets of processes of connection and disconnection, merging and splitting of “nuclei” (atomism) where interactions are clearly visible. Through art, thought of as the porous structure of society with permeable sites of relation, each image and each material form of an artwork is only a connective element with values and other forms that are transferable in society. This is a principle of dynamic connection in which form is a kind of representation and a potential condition of exchange. The in-between zone has been distinguished, bearing its own traditions and recognizing both the connectedness as well as the separate items that are connected. Fluid culture atomism (fluid atomism) is where we observe the dynamics in interactions in an ever-changing structure that is itself made up of separated atomic units briefly grouped into more complex molecular formations, with all the connections between them being impermanent and temporary. Both the internal structures and the state of the whole change. The interactions of individual units are a key factor in the analysis of processes in art. These processes are embedded in perishable, dynamically transforming networks of ‘private’ art worlds, the sum of which is not the Universal World but a momentary state in an ever-changing system. The relationship between the individual artist and the overall system of organized artistic life passes through interactions of a socialpsychological type in organized temporary groups of artists. This article discusses the possible relations between the field of social psychology and art. Emphasis is placed on the aspects of innovative artistic inquiry, discussed as the singular and the unique in art as opposed to the established order. Innovation in art is juxtaposed with innovation in social bonding as a social psychological problem of creativity. Individual creativity is compared to the creativity of groups and the particularities of the creative processes inherent to individual artists. Such an interpretation develops further the idea of an art world seen as impermanent and dynamically changing networks of ‘private’ art worlds. Among the autonomous zones defined by the individual and the group are found shared zones through which polar differences are harmonized. Individual artistic innovation is juxtaposed with innovative practices that are formed through the action of the groups.

Role of van der Waals, Electrostatic, and Hydrogen-Bond Interactions for the Relative Stability of Cellulose Iβ and II Crystals.

Naturally occurring cellulose Iβ with its characteristic parallel orientation of cellulose chains is less stable than cellulose II, in which neighboring pairs of chains are oriented antiparallel to each other. While the distinct hydrogen-bond patterns of these two cellulose crystal forms are well established, the energetic role of the hydrogen bonds for crystal stability, in comparison to the van der Waals (vdW) and overall electrostatic interactions in the crystals, is a matter of current debate. In this article, we investigate the relative stability of celluloses Iβ and II in energy minimizations with classical force fields. We find that the larger stability of cellulose II results from clearly stronger electrostatic interchain energies that are only partially compensated for by stronger vdW interchain energies in cellulose Iβ. In addition, we show that a multipole description of hydrogen bonds that includes the COH groups of donor and acceptor oxygen atoms leads to consistent interchain hydrogen-bond energies that account for roughly 70% and 75% of the interchain electrostatics in celluloses Iβ and II, respectively.

Preparation and Antifungal Properties of Cyclopropyl Derivatives of 3-Aminoquinazolin-4(3H)-one and Salicylal Schiff Base Nickel(II) Chelate Complex

N-substituted 2-cyclopropyl-3-R-quinazoline-4()-ones [R: NH2 (1), N=CH(2-hydroxyphenyl) (2)] and Ni(II) chelate compound of 2-cyclopropyl-3-[(Z)-(2-hydroxybenzylidene)amino]quinazoline-4(3H)-one (3) were synthesized and their structures and properties were characterized using X-ray diffraction data, computational optimization, 1H and 13C NMR, IR spectroscopy, and diffuse reflectance spectra. Compounds 1 and 2 are monoclinic (space group P21/n). Unit cell parameters (a, b, c) are 9.2529; 4.7246; 22.3460 Å and 10.2811; 4.6959; 30.972 Å for 1 and 2, respectively. Nickel(II) chelate compound crystallizes in an orthorhombic crystal system (space group Pbca). Unit cell parameters (a, b, c) for 3 are 26.5010; 14.8791; 8.904975 Å, respectively. Schiff base 2 in the crystalline state exhibits two rotary isomers in a molar ratio of 1:3, among which only a minor component as a bidentate ligand can form compound 3 with Ni(II) ion. Nickel(II) ion in 3 is coordinated by N donor atoms and deprotonated O atoms of Schiff base ligands to form square-planar chelate node NiN2O2. All synthesized compounds revealed high antifungal activity against bread mold (Mucor mucedo).

Crown-like Biodegradable Lipids Enable Lung-Selective mRNA Delivery and Dual-Modal Tumor Imaging In Vivo.

Systemic mRNA delivery to specific cell types remains a great challenge. We herein report a new class of crown-like biodegradable ionizable lipids (CBILs) for predictable lung-selective mRNA delivery by leveraging the metal coordination chemistry. Each CBIL contains an impressive crown-like amino core that coordinates with various metal ions such as Zn2+ and further regulates the in vivo organ-targeting behavior of lipid nanoparticles (LNPs). The representative CBIL (Zn-9C-SCC-10)-formulated LNPs could exclusively deliver mRNA to the lung after systemic administration. Notably, following intravenous administration of 0.2 mg kg-1 Cre mRNA, Zn-9C-SCC-10 LNPs enabled the highly efficient gene editing of all lung epithelial and endothelial cells up to 43 and 61%, respectively, outperforming the current state-of-the-art LNPs in lung epithelial cell delivery. Moreover, compared to DLin-MC3-DMA LNPs with the addition of cationic lipid (DOTAP), our approach yielded a 44.6-fold enhancement in pulmonary mRNA expression and significantly improved biosafety in vivo. Taking advantage of paramagnetic gadolinium ion, Gd-12C-SCC-10 LNPs allowed the potent mRNA delivery to cancer cells and successfully illuminated lung tumors by magnetic and bioluminescent dual-mode imaging, facilitating the early discovery and diagnosis of lung cancer. This work will open a new avenue to rationally design predictable LNPs, as well as address the major challenges of mRNA delivery to specific cells in the lung tissues for treating a wide variety of diseases.

A Review: Recent Advances in Chemistry and Applications of 2,4-Dihydroxybenzaldehyde Oxime and Its Transition Metal Complexes

This review presents a comprehensive overview of the recent advances in the chemistry and applications of 2,4-dihydroxybenzaldehyde oxime (DHBO) and its transition metal complexes. DHBO, characterized by its unique hydroxyl and oxime functional groups, has gained significant attention due to its versatile reactivity and potential applications across various fields, including pharmaceuticals, catalysis, and environmental science. Recent synthetic methodologies, including microwave-assisted techniques and green chemistry approaches, have improved the efficiency and sustainability of DHBO production. The formation of transition metal complexes with DHBO has been a focal point of research, revealing enhanced catalytic properties and biological activities compared to the free ligand. These complexes have shown promise in organic synthesis, particularly in oxidation and reduction reactions, as well as in drug development, exhibiting antimicrobial and anticancer properties. Furthermore, the potential of DHBO and its metal complexes in environmental remediation, particularly in removing heavy metals and pollutants, underscores their significance in addressing contemporary environmental challenges. This review also provides current knowledge on the synthesis, characterization, and applications of DHBO and its transition metal complexes, highlighting their importance in both academic research and industrial applications. By elucidating the multifaceted roles of DHBO, this work aims to pave the way for future research and innovation in this promising area of study.