Steric Features Research Articles

Advanced Equilibrium Studies for the Synergetic Impact of Polyaniline on the Adsorption of Rhodamine B Dye by Polyaniline/Coal Composite.

The synergetic improvement effect of the polyaniline (PANI) hybridization process on the adsorption of rhodamine B dye (RB) by PANI/coal hybrid material (PANI/C) has been evaluated using both traditional equilibrium modeling and advanced isotherm investigations. The composite was prepared by polymerizing polyaniline in the presence of coal fractions with a surface area of 27.7 m2/g. The PANI/C hybrid has an improved capacity to adsorb RB dye (423.5 mg/g) in comparison to coal particles (254.3 mg/g). The maintained increase in the elimination properties of PANI/C has been illustrated using the steric characteristics of active site density (Nm) as well as the total number of adsorbed RB on a single active site (n). However, the incorporation of PANI did not yield any substantial impact on the existing active sites' quantity, but the hybridization processes greatly influenced the selectivity and affinity of each active site, in addition to the aggregation characteristics of the dye as it interacts with the composite's surface. Whereas raw coal can only adsorb three molecules of RB, each active site throughout the PANI/C surface can adsorb approximately eight RB molecules. This is also evidence of RB dye adsorption in a vertical arrangement, which involves multimolecular processes. The Gaussian energy (4.01-5.59 kJ/mol) and adsorption energy (-4.34-4.68 kJ/mol) revealed the controllable impact of physical mechanisms. These mechanisms may include van der Waals forces, dipole-dipole interactions, and hydrogen bonds (<30 kJ/mol). The thermodynamic functions, such as enthalpy, internal energy, and entropy, that have been assessed provide evidence supporting the exothermic and spontaneous nature of the RB uptake processes by PANI/C.

Poly(imidazolyliden-yl)borato Complexes of Tungsten: Mapping Steric vs. Electronic Features of Facially Coordinating Ligands.

A convenient synthesis of [HB(HImMe)3](PF6)2 (ImMe = N-methylimidazolyl) is decribed. This salt serves in situ as a precursor to the tris(imidazolylidenyl)borate Li[HB(ImMe)3] pro-ligand upon deprotonation with nBuLi. Reaction with [W(≡CC6H4Me-4)(CO)2(pic)2(Br)] (pic = 4-picoline) affords the carbyne complex [W(≡CC6H4Me-4)(CO)2{HB(ImMe)3}]. Interrogation of experimental and computational data for this compound allow a ranking of familiar tripodal and facially coordinating ligands according to steric (percentage buried volume) and electronic (νCO) properties. The reaction of [W(≡CC6H4Me-4)(CO)2{HB(ImMe)3}] with [AuCl(SMe2)] affords the heterobimetallic semi-bridging carbyne complex [WAu(μ-CC6H4Me-4)(CO)2(Cl){HB(ImMe)3}].

Interaction of anti-inflammatory drug nimesulide with ionic and non-ionic surfactant micelles: Insights from spectral and bioinformatics approach

The present work reports the interaction of anti-inflammatory drug nimesulide with cationic (CTAB, HDPC), anionic (SDS) and non-ionic (Triton X-100) surfactant micelles. The drug-micelles systems were studied by UV–Vis absorption spectroscopy to estimate the binding constant (Kb), partition coefficient (Kx) and the free energy of binding and partition (ΔGb, ΔGx). The values of Kb indicate a stronger interaction between nimesulide and cationic micelles due to cumulative electrostatic and hydrophobic forces. Also, the higher values of Kx obtained for HDPC and CTAB micelles point out a higher drug concentration in cationic micelles than in the surrounding aqueous medium, as against SDS and Triton X-100 micelles. The bioinformatic methods were used to evaluate the pharmacokinetic, pharmacogenomic and pharmacodynamic profiles of the nimesulide, CTAB, HDPC, SDS, and Triton X-100. Our results showed that all compounds exhibit good intestinal absorption, good BBB and CNS permeabilities, and low toxicity features. Also, the ecotoxicity of compounds was quantified. Various pharmacogenomic features of compounds were recorded. Supplementary, we conducted an extensive analysis based on various aspects of the structural and functional features of compounds, such as their electronic (dipole moment, frontiers orbital energies), steric, and hydrophobic features. Experimental and theoretical results show that CATB and HDPC cationic micelles may be better drug delivery agents for nimesulide.

Encapsulation of Palladium Carbide Subnanometric Species in Zeolite Boosts Highly Selective Semihydrogenation of Alkynes.

The selective hydrogenation of alkynes to alkenes is a crucial step in the synthesis of fine chemicals. However, the widely utilized palladium (Pd)-based catalysts often suffer from poor selectivity. In this work, we demonstrate a carbonization-reduction method to create palladium carbide subnanometric species within pure silicate MFI zeolite. The carbon species can modify the electronic and steric characteristics of Pd species by forming the predominant Pd-C4 structure and, meanwhile, facilitate the desorption of alkenes by forming the Si-O-C structure with zeolite framework, as validated by the state-of-the-art characterizations and theoretical calculations. The developed catalyst shows superior performance in the selective hydrogenation of alkynes over mild conditions (298 K, 2 bar H2 ), with 99 % selectivity to styrene at a complete conversion of phenylacetylene. In contrast, the zeolite-encapsulated carbon-free Pd catalyst and the commercial Lindlar catalyst show only 15 % and 14 % selectivity to styrene, respectively, under identical reaction conditions. The zeolite-confined Pd-carbide subnanoclusters promise their superior properties in semihydrogenation of alkynes.

Encapsulation of Palladium Carbide Subnanometric Species in Zeolite Boosts Highly Selective Semihydrogenation of Alkynes

AbstractThe selective hydrogenation of alkynes to alkenes is a crucial step in the synthesis of fine chemicals. However, the widely utilized palladium (Pd)‐based catalysts often suffer from poor selectivity. In this work, we demonstrate a carbonization‐reduction method to create palladium carbide subnanometric species within pure silicate MFI zeolite. The carbon species can modify the electronic and steric characteristics of Pd species by forming the predominant Pd−C4 structure and, meanwhile, facilitate the desorption of alkenes by forming the Si−O−C structure with zeolite framework, as validated by the state‐of‐the‐art characterizations and theoretical calculations. The developed catalyst shows superior performance in the selective hydrogenation of alkynes over mild conditions (298 K, 2 bar H2), with 99 % selectivity to styrene at a complete conversion of phenylacetylene. In contrast, the zeolite‐encapsulated carbon‐free Pd catalyst and the commercial Lindlar catalyst show only 15 % and 14 % selectivity to styrene, respectively, under identical reaction conditions. The zeolite‐confined Pd‐carbide subnanoclusters promise their superior properties in semihydrogenation of alkynes.

Transduction of Amine-Phosphate Supramolecular Interactions and Biosensing of Acetylcholine through PEDOT-Polyamine Organic Electrochemical Transistors.

Organic electrochemical transistors (OECTs) are important devices for the development of flexible and wearable sensors due to their flexibility, low power consumption, sensitivity, selectivity, ease of fabrication, and compatibility with other flexible materials. These features enable the creation of comfortable, versatile, and efficient portable devices that can monitor and detect a wide range of parameters for various applications. Herein, we present OECTs based on PEDOT-polyamine thin films for the selective monitoring of phosphate-containing compounds. Our findings reveal that supramolecular single phosphate-amino interaction induces higher changes in the OECT response compared to ATP-amino interactions, even at submillimolar concentrations. The steric character of binding anions plays a crucial role in OECT sensing, resulting in a smaller shift in maximum transconductance voltage and threshold voltage for bulkier binding species. The OECT response reflects not only the polymer/solution interface but also events within the conducting polymer film, where ion transport and concentration are affected by the ion size. Additionally, the investigation of enzyme immobilization reveals the influence of phosphate species on the assembly behavior of acetylcholinesterase (AchE) on PEDOT-PAH OECTs, with increasing phosphate concentrations leading to reduced enzyme anchoring. These findings contribute to the understanding of the mechanisms of OECT sensing and highlight the importance of careful design and optimization of the biosensor interface construction for diverse sensing applications.

Unraveling the mechanistic details of rho-associated coiled-coil kinase1 (ROCK1) inhibition: Implications from pharmacophore mapping and free energy analysis

Rho-associated coiled-coil kinases (ROCKs) are essential for various cellular processes and play a crucial role in neurological and inflammatory disorders. The two ROCK isoforms (ROCK1 and ROCK2) are involved in the pathogenesis of multiple diseases. Increased levels of ROCK1 are observed in patients with Alzheimer's disease (AD), making it a promising drug target. This work presents the mechanism of inhibitor binding at the ROCK1 active site using a combination of ligand and structure-based drug design techniques. Ligand-based pharmacophore studies were performed on previously reported ROCK1 inhibitors to unravel the 3D steric and electronic features essential for ROCK1 inhibition. Molecular docking and molecular dynamics-based free energy analysis studies were performed to recognize the amino acids assisting in inhibitor binding by stabilizing the identified pharmacophore features. The crucial 3D pharmacophore features of ROCK1 inhibitors included hydrophobic (HYD), hydrogen-bond acceptor (HBA), and hydrogen-bond donor (HBD) characteristics. These features were oriented next to the complementary amino acids in the ROCK1 active site, as evident from the detailed interaction analysis. The free energy calculations provided a quantifiable estimate of the favorable energetic contribution of Gly83, Val90, Lys105, Asp160, Leu205, and Asp216 to the total binding energy. These amino acids significantly contributed to the ROCK1-inhibitor complexes' overall binding free energy, indicating their importance in inhibitor binding.

Experimental and Theoretical Study of Methylene Blue Adsorption on a New Raw Material, Cynara scolymus—A Statistical Physics Assessment

Methylene blue (MB) adsorption was performed on a natural material powder of Cynara scolymus as a new inexpensive adsorbent identified by Cs. To analyze the Cs material, FTIR, SEM, isoelectric point (pHpzc) analysis, TGA, and DRX were used. The maximum experimental adsorption capacity of the Cs material was 203.333, 192.187, and 179.380 mg•g−1 at 298, 303, and 313 K, respectively. The correlation coefficients (R2) and average percentage errors APE (%) values for the kinetic and isotherms models indicated that the adsorption kinetics followed a pseudo-nth order model and that the traditional isotherm model Redlich–Peterson (R–P) correctly described the experimental data obtained at 298, 303, and 313 K, respectively. The steric, energetic, and thermodynamic characteristics of the most relevant advanced model (double-energy single-layer model (AM 2)) were analyzed in detail. The number of active sites for the first receptors (n1) was determined to be 0.129, 0.610, and 6.833, whereas the number of second active sites (n2) was determined to be 1.444, 1.675, and 2.036 at 298, 303, and 313 K, respectively. This indicated the presence of both multi–docking and multimolecular modes for the first style of MB ions (n1), while only a multimolecular mode for the second style of MB ions (n2). Thermodynamic characteristics demonstrated that MB adsorption onto the Cs adsorbent is spontaneous and feasible.

Employing Click Chemistry to Expand the Scope of the Metal‐Free Donor‐Acceptor‐Type Photocatalyst 4CzIPN

AbstractThe design of a versatile alkyne‐bearing derivative of the donor‐acceptor fluorophore 2,4,5,6‐tetrakis(9H‐carbazol‐9‐yl) isophthalonitrile (4CzIPN) suitable for further targeted modifications by copper‐catalysed Azide Alkyne Cycloaddition (CuAAC) is reported. The newly synthesised photoredox catalyst notably exhibits analogously unique photoelectronic and steric features as the well‐established carbazolyl dicyanobenzene motif and performs equally in a C−C‐Coupling model reaction. Furthermore, the variability of this donor‐acceptor system was demonstrated by the generation of a library of fourteen photoredox catalysts with electron‐withdrawing and ‐donating groups as well as residues with high steric demands in one simple and selective CuAAC reaction. The modified catalysts feature a broad scope of reducing and oxidising powers in their excited states (span of reducing powers over more than 1 V) and were also successfully applied in the photoredox and nickel‐catalysed decarboxylative cross coupling model reaction. This work represents a method to overcome the limitations in the flexibility of metal‐free donor‐acceptor fluorophores required for the targeted application in organic synthesis and paves the way for the design of customised catalysts with multiple functionalities.

New Insights into the Catalytic Activity of Second Generation Hoveyda–Grubbs Complexes Having Phenyl Substituents on the Backbone

One of the most effective synthetic pathways to produce unsaturated compounds and polymers, meant for both industrial and pharmaceutical applications, is olefin metathesis. These useful reactions are commonly promoted by ruthenium-based precatalysts, namely the second-generation Grubbs’ catalyst (GII) and complexes bearing a styrenyl ether ligand, referred to as the second-generation Hoveyda–Grubbs’ catalyst (HGII). By altering the steric and electronic characteristics of substituents on the backbone and/or on the nitrogen atoms of the NHC ligand, it is possible to increase the reactivity and stability of second-generation ruthenium catalysts. The synthesis of an HG type II complex bearing two anti-phenyl backbone substituents (anti-HGIIPh-Mes) with mesityl N-substituents is reported. The catalytic performances of the new complex were investigated in standard ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROMP) and compared to those of the analogue complex syn-HGIIPh-Mes and to the classic HGII complex. A thorough analysis of the temperature dependence of the performances, along with a detailed comparison with the commercially available HGII, is conducted. The HGIIPh-Mes complexes are more thermally stable than their parent HGII, as shown by the fact that their activity in the ROMP of 5-ethylidene-2-norbornene does not alter when the polymerization is carried out at room temperature after the complexes have been held at 180 °C for two hours, making them particularly interesting for materials applications.

Selection of potential natural compounds for poly-ADP-ribose polymerase (PARP) inhibition in glioblastoma therapy by in silico screening methods

Glioblastoma (GBM), the most prevalent brain tumor, is one of the least treatable malignancies due to its propensity for intracranial spread, high proliferative potential, and innate resistance to radiation and chemotherapy. Current GBM therapy is limited due to unfavorable, non-specific therapeutic effects in healthy cells and the difficulty of small molecules to penetrate the blood brain barrier (BBB) and reach the tumor microenvironment. Adding PARP-1 inhibitors inhibit DNA repair enzymes thereby increasing the cytotoxicity of anticancer agents. Hence, we aimed to discover potential naturally occurring PARP-1 inhibitors that can be utilized in the treatment of glioma by using multiple in silico tools like molecular docking, absorption, distribution, metabolism, and excretion (ADME) profile, pharmacophore modeling, and molecular dynamic (MD) simulations. Among 43 phytocompounds we screened, two of them (Ellagic acid and Naringin) were discovered to be bound to the catalytic site of PARP-1 with an affinity more remarkable than commercially available PARP-1 inhibitors (Talazoparib, Niraparib, and Rucaparib) except Olaparib. The molecular interactions were analyzed, and data shows that bound entity attained a conserved domain via hydrogen bond interactions, polar interactions, and π-π stacking. Pharmacophore modeling studies showed electronic and steric features of ligands responsible for supramolecular interaction with PARP-1. ADME properties were studied, to assess drug-likeness, hydrophilic nature, hydrophobicity, brain permeability, and oral bioavailability of the natural PARP-1 inhibitors. The simulation study demonstrated the development of a stable complex between Naringin, Ellagic acid, and PARP-1 protein. Moreover, cell culture studies and animal investigations are essential to determine pharmacokinetics and pharmacodynamics.

Formal [3 + 2] Cycloaddition of α-Imino Esters with Azo Compounds: Facile Construction of Pentasubstituted 1,2,4-Triazoline Skeletons.

1,2,4-Triazole and 1,2,4-triazoline are important components of bioactive molecules and catalysts employed in organic synthesis. Therefore, the efficient synthesis of these components has received significant research attention. However, studies on their structural diversity remain lacking. Previously, we developed chiral phase-transfer-catalyzed asymmetric reactions of α-imino carbonyl compounds with α,β-unsaturated carbonyl compounds and haloalkanes. In this study, we demonstrate the formal [3 + 2] cycloaddition reaction of α-imino esters with azo compounds under Brønsted base catalysis, resulting in the corresponding 1,2,4-triazolines in high yields. The results revealed that a wide range of substrates and reactants can be applied, irrespective of their steric and electronic characteristics. The present reaction made the general preparation of 3-aryl pentasubstituted 1,2,4-triazolines possible for the first time. Furthermore, a mechanistic study suggested that the reaction proceeds without isomerization into the aldimine form.

Metaphore Biotechnologies launches with molecular mimicry platform

After 2 years of development at Flagship Pioneering, the start-up Metaphore Biotechnologies emerged on May 16 with $50 million of series A funding. It plans to tackle autoimmune and metabolic diseases, as well as cancer. Metaphore’s approach to drug discovery is to mimic and improve on pharmacophores—abstractions that describe the steric and electronic features needed for bioactive molecules to interact with a biological target and unlock a response in the body. “It all started actually with us asking the question: What if we could mimic any molecular interaction in a programmable way?” says Lovisa Afzelius, Metaphore’s CEO and cofounder. The company condenses the key interaction points of these pharmacophores and then builds a “mold.” This computational framework narrows down the potential molecular solutions from the vast chemical space available, making the optimization problem easier to solve. When building new compounds inside this mold, researchers use machine learning to optimize the

Bimolecular Reductive Elimination of Ethane from Pyridine(diimine) Iron Methyl Complexes: Mechanism, Electronic Structure, and Entry into [2+2] Cycloaddition Catalysis.

The application of bimolecular reductive elimination to the activation of iron catalysts for alkene-diene cycloaddition is described. Key to this approach was the synthesis, characterization, electronic structure determination, and ultimately solution stability of a family of pyridine(diimine) iron methyl complexes with diverse steric properties and electronic ground states. Both the aryl-substituted, (MePDI)FeCH3 and (EtPDI)FeCH3 (RPDI = 2,6-(2,6-R2-C6H3N═CMe)2C5H3N), and the alkyl-substituted examples, (CyAPDI)FeCH3 (CyAPDI = 2,6-(C6H11N═CMe)2C5H3N), have molecular structures significantly distorted from planarity and S = 3/2 ground states. The related N-arylated derivative bearing 2,6-di-isopropyl aryl substituents, (iPrPDI)FeCH3, has an idealized planar geometry and exhibits spin crossover behavior from S = 1/2 to S = 3/2 states. At 23 °C under an N2 atmosphere, both (MePDI)FeCH3 and (EtPDI)FeCH3 underwent reductive elimination of ethane to form the iron dinitrogen precatalysts, [(MePDI)Fe(N2)]2(μ-N2) and [(EtPDI)Fe(N2)]2(μ-N2), respectively, while (iPrPDI)FeCH3 proved inert to C-C bond formation. By contrast, addition of butadiene to all three iron methyl complexes induced ethane formation and generated the corresponding iron butadiene complexes, (RPDI)Fe(η4-C4H6) (R = Me, Et, iPr), known precatalysts for the [2+2] cycloaddition of olefins and dienes. Kinetic, crossover experiments, and structural studies were combined with magnetic measurements and Mössbauer spectroscopy to elucidate the electronic and steric features of the iron complexes that enable this unusual reductive elimination and precatalyst activation pathway. Transmetalation of methyl groups between iron centers was fast at ambient temperature and independent of steric environment or spin state, while the intermediate dimer underwent the sterically controlled rate-determining reaction with either N2 or butadiene to access a catalytically active iron compound.

Synthesis of Adagrasib (MRTX849), a Covalent KRASG12C Inhibitor Drug for the Treatment of Cancer

A concise, transition-metal and protection-free synthesis of adagrasib (MRTX849), a novel KRASG12C inhibitor drug recently approved by the FDA, is reported. Introduction of two chiral building blocks to the tetrahydropyridopyrimidine core was accomplished via two sequential SNAr reactions. Extensive reaction optimization led to a robust, transition-metal-free oxidation of the sulfide intermediate. A judicious choice of the leaving group with favorable steric and electronic characteristics at the 4-OH position of the tetrahydropyridopyrimidine core enabled a facile SNAr displacement to introduce the chiral piperazine. This new, five-step, chromatography-free synthesis of adagrasib from readily available starting materials obviated the palladium catalysis and protecting group manipulations in the current commercial route and significantly improved the efficiency of the process in 45% overall yield.

Voltage sensor targeted activation of Kv7 channels by QO-58.

Kv7 (KCNQ) voltage-gated potassium channels are key modulators of neuronal excitability and have been a promising target for developing novel drugs to treat epilepsy and pain. Drug discovery has focused on identifying small molecules that modulate channel function and understanding their mechanisms of action. Special attention has been given to Kv7 channel activators, which may have therapeutic benefits in epilepsy or pain. In this study, we compared the effects and mechanism of a candidate Kv7 activator, QO-58, which has been previously described but has an unclear site and mechanism of action. We compared QO-58 actions with other well-characterized activators that influence either the VSD (ICA-069673) or pore domain (ML213) of Kv7 channels. QO-58 exhibits strong subtype specificity for Kv7.2 over Kv7.3, similar to VSD-targeted activators. Additionally, QO-58 exhibits prominent state-dependent actions, as it requires channels to activate before binding, and dramatically decelerates closure of Kv7.2. We also tested the effects of multiple VSD mutations on QO-58 and ICA-069673 actions. Interestingly, we found that the Kv7.2[F168L] mutation, previously shown to abolish ICA-069673 sensitivity, does not markedly affect QO-58 mediated effects. Notably, Kv7.2[I134A] and Kv7.2[I173T] weaken the effects of ICA-069673, but are hypersensitive to QO-58. This finding may suggest that dimensions of the VSD binding pocket influence the potency of smaller compounds (e.g. ICA-069673) relative to bulkier ones (e.g. QO-58), despite overlap in their binding sites. Our findings highlight that key contacts underlying sensitivity to VSD-targeted activators may vary significantly depending on the chemical and steric features of the drug. We anticipate that further investigation of VSD-targeted activators will continue to clarify the complex pharmacophore of the VSD binding pocket in Kv7 channels.

Electronic and Steric Effects on L‐Lactide Ring‐Opening Polymerization with NSSN‐type Zr(IV) Complexes

AbstractIn this work the mechanism of L‐lactide polymerization promoted by NSSN zirconium complexes was investigated through DFT methods with the aim to understand as the electronic and steric features of the ligand affect the energy reaction. It was observed that the rate determining step of the process is the opening of the L‐lactide ring and that by increasing the steric hindrance, evaluated by changing geometric parameters and topographic steric maps, or the electron‐withdrawing properties of the ligand, the corresponding energy barrier increases. On the other hand, calculations foresee that a small and electron‐releasing substituent on the nitrogen atom of the ligand, such as the methyl group, is desirable in order to obtain NSSN zirconium based catalysts with improved activity in the ROP of the L‐lactide.

Enantioselective Michael addition of malonates to β,γ-unsaturated α-ketoesters catalysed by Cu(II) complexes bearing binaphthyl-proline hybrid ligands.

High yields (up to 96%) and high ee (up to 92%) were achieved for chiral copper(II) complex-catalysed enantioselective Michael addition of malonates to β,γ-unsaturated-α-ketoesters. The chiral ligands took advantage of both the binaphthyl and the proline moieties, and substituents with different electronic and steric features could be tolerated. The reactions could be carried out under mild conditions, and a gram scale reaction could be realised without the loss of yield and enantioselectivity.

Filling the gap with a bulky diaryl boron group: fluorinated and non-fluorinated copper pyrazolates fitted with a dimesityl boron moiety on the backbone.

Successful synthesis has been reported of 4-Mes2B-3,5-(CF3)2PzH and 4-Mes2B-3,5-(CF3)2PzH bearing sterically demanding diarylboron moieties at the pyrazole ring 4-position, and their corresponding copper(I) pyrazolate complexes. They show visible blue photoluminescence in solution. The X-ray crystal structures revealed that the fluorinated {[4-BMes2-3,5-(CF3)2Pz]Cu}3 crystallizes as discrete trinuclear molecules whereas as the non-fluorinated {[4-BMes2-3,5-(CH3)2Pz]Cu}3 forms dimers of trimers with two close inter-trimer Cu⋯Cu separations. The solid {[4-BMes2-3,5-(CF3)2Pz]Cu}3 featuring a sterically confined Cu3N6 core displays bright blue phosphorescence while {[4-BMes2-3,5-(CH3)2Pz]Cu}3, which is a dimer of a trimer, is a red phosphor at room temperature. This work illustrates the modulation of photo-physical properties of metal pyrazolates by adjusting the supporting ligand steric features and introducing secondary diarylboron luminophores. Computational analysis of the structures and photophysical properties of copper complexes are also presented.

Dual aromatase-steroid sulfatase inhibitors (DASI's) for the treatment of breast cancer: a structure guided ligand based designing approach

Dual aromatase-steroid sulfatase inhibitors (DASIs) lead to significant deprivation of estrogen levels as compared to a single target inhibition and thereby exhibited an additive or synergistic effect in the treatment of hormone-dependent breast cancer (HDBC). Triazole-bearing DASI’s having structural features of clinically available aromatase inhibitors are identified as lead structures for optimization as DASI’s. To identify the spatial fingerprints of target-specific triazole as DASI’s, we have performed molecular docking assisted Gaussian field-based comparative 3D-QSAR studies on a dataset with dual aromatase-STS inhibitory activities. Separate contours were generated for both aromatase and steroid sulphates showing respective pharmacophoric structural requirements for optimal activity. These developed 3D-QSAR models also showed good statistical measures with the excellent predictive ability with PLS-generated validation constraints. Comparative steric, electrostatic, hydrophobic, HBA, and HBD features were elucidated using respective contour maps for selective target-specific favourable activity. Furthermore, the molecular docking was used for elucidating the mode of binding as DASI’s along with the MD simulation of 100 ns revealed that all the protease-ligand docked complexes are overall stable as compared to reference ligand (inhibitor ASD or Irosustat) complex. Further, the MM-GBSA study revealed that compound 24 binds to aromatase as well as STS active site with relatively lower binding energy than reference complex, respectively. A comparative study of these developed multitargeted QSAR models along with molecular docking and dynamics study can be employed for the optimization of drug candidates as DASI’s. Communicated by Ramaswamy H. Sarma