Position Of Nitrogen Atom Research Articles

The Chemistry and Biological Effects of Fused 1,2,4-triazolo[4,3-c]pyrimidines and their Isomeric 1,2,4-triazolo[1,5-c]pyrimidines

Concerning polycyclic heterocyclic compounds, fused triazolopyrimidines and their substituted analogs have been studied recently from a chemical and biological point of view. Triazolopyrimidines have eight different positional isomers based on their structural arrangement and nitrogen atom positions. The present review concerns synthesizing 1,2,4- triazolo[4,3-c]pyrimidines and 1,2,4-triazolo[1,5-c]pyrimidines fused with a fivemembered ring containing one heteroatom. The 1,2,4-triazolo[4,3-c]pyrimidines can be prepared by closing the triazole ring on the 4-hydrazinopyrimidine ring, and the 1,2,4- triazolo[1,5-c]pyrimidines can be prepared by closing the triazole ring on the 4- iminopyrimidine-3-amine ring. The transformation of 1,2,4-triazolo[4,3-c]pyrimidine to the more thermodynamically stable isomer triazolo[1,5-c]pyrimidine derivatives via Dimroth rearrangement under different reaction conditions is also discussed. Moreover, the biological activity of both series is presented.

Antimicrobial Activity of Naphthyridine Derivatives.

To combat the problem of the increasing drug resistance of microorganisms, it is necessary to constantly search for new medicinal substances that will demonstrate more effective mechanisms of action with a limited number of side effects. Naphthyridines are N-heterocyclic compounds containing a fused system of two pyridine rings, occurring in the form of six structural isomers with different positions of nitrogen atoms, which exhibit a wide spectrum of pharmacological activity, in particular antimicrobial properties. This review presents most of the literature data about the synthetic and natural naphthyridine derivatives that have been reported to possess antimicrobial activity.

Catalytic Electrodes for the Oxygen Reduction Reaction Based on Co-Doped Carbon Quantum Dots and Anion Exchange Ionomer

The sluggish kinetics of the oxygen reduction reaction (ORR), more than six orders of magnitude slower than the hydrogen oxidation reaction in acidic conditions, is a major concern for various energy storage and conversion devices, including metal air batteries and fuel cells. The exceptionally high O––O bond energy (~500 kJ/mol) requires generally the use of noble-metal electrocatalysts, including platinum and palladium, for the four-electron reduction in acidic conditions.The ORR is however faster in alkaline medium and non-noble electrocatalysts are applicable, including doped carbon materials. Nanostructured carbons have especially retained the attention due to their solubility in organic solvents that make the drop-casting procedure available. The electroactivity of carbon quantum dots (CQD) for the ORR was demonstrated in 2012.We have recently compared the preparation of CQD by three different methods -pyrolysis, microwave irradiation and hydrothermal synthesis - and reported their respective properties. The hydrothermal method is most promising due to the easily controllable composition and structure via the optimization of precursors and can produce CQD with uniform particle size. We showed especially that the position of nitrogen atoms in the nanostructure, for example in graphitic, pyrrolic or pyridinic sites, changes significantly the properties of the CQD.In this work, we therefore investigate a simple and easily up-scalable synthesis of heteroatom co-doped CQD, using inexpensive starting materials and a fast hydrothermal synthesis procedure, which provides uniform CQD size. The CQD are characterized by various techniques, including XPS, FTIR, and Raman spectroscopy.The overpotential of the ORR contains the activation overpotential that can be reduced by the presence of a potent electrocatalyst improving the charge transfer kinetics, the Ohmic drop and the diffusion overpotential, related to the transport of oxygen gas and of hydroxide ions. Whereas the oxygen diffusion can be facilitated by the microstructure of the electrode, the hydroxide ion transport is enhanced by the presence of an anion exchange ionomer (AEI) in the electrode. The ORR occurs at the triple phase boundary between gas phase (pore), electron conducting catalyst (carbon paper/CQD) and hydroxide ion conductor (AEI), here poly(sulfone trimethylammonium hydroxide) (PSU-TMA).The electrodes investigated in this work are therefore prepared by drop-casting on carbon paper of a slurry containing co-doped CQD and AEI. Impedance spectroscopy and d.c. capacitance measurements are used to determine the electrochemically active surface area of the electrodes. The electrocatalytic activity for the ORR is studied in alkaline conditions (1 M KOH) by cyclic (CV) and linear sweep voltammetry (LSV) at various speeds of a rotating disk electrode (RDE). A.R. Nallayagari, E. Sgreccia, R. Pizzoferrato, M. Cabibbo, S. Kaciulis, E. Bolli, L. Pasquini, P. Knauth, M.L. Di Vona, Tuneable properties of carbon quantum dots by different synthetic methods, J. Nanostruct. Chem. 12 (2022) 565–580. A.R. Nallayagari, E. Sgreccia, L. Pasquini, F. Vacandio, S. Kaciulis , M.L. Di Vona, P. Knauth , Catalytic electrodes for the oxygen reduction reaction based on co-doped (B-N, Si-N, S-N) carbon quantum dots and anion exchange ionomer, Electrochemica Acta 427 (2022) 140861.

Synthesis and preclinical evaluation of diarylamine derivative as Tau-PET radiotracer for Alzheimer's Disease

The presence of aggregated Tau in the brain is a dominant pathological hallmark of Tauopathies, particularly in Alzheimer's disease (AD). Therefore, developing ligands that can specifically and sensitively bind to Tau aggregates is essential for diagnosing and monitoring therapeutic interventions. In this study, we further investigated the structural optimization of the diarylamine skeleton, which exhibited promising binding characteristics and biological properties. We supplementarily explored the effects of the number and position of nitrogen atoms, types of heteroatoms and aromatic moieties, and radioactive positions on affinity for Tau. Through a structure-activity relationship (SAR) analysis based on 125I-labeled diarylamine derivatives, [125I]A6 was identified as a lead compound due to its desirable binding properties and ability to penetrate the brain, making it suitable for conversion into a18F-labeled PET tracer. Satisfactorily, [18F]FA1 fulfilled critical requirements as a Tau radiotracer, demonstrating high specificity and selectivity for Tau, a clean off-target profile against Aβ plaques and monoamine oxidase B (MAO-B), and favorable in vivo brain kinetics, as confirmed by dynamic PET studies in rodents and non-human primates.

Determination of pKa of triazolo[5,1-c][1,2,4]triazines in non-aqueous media by potentiometric titration

In this work, for the first time, an approach was suggested for determining the pKa of triazolo[5,1-c][1,2,4]triazine compounds in N,N-dimethylformamide using potentiometric titration. It was noted that change in system potential in the titration curves of triazolo[5,1-с][1,2,4]triazine are observed for compounds containing either H+ located at the nitrogen atom in position 1 or an –NH2 group. The calculated pKa values of the studied molecules correspond to the pKa values of moderately strong acids and are in the range of 2–8. The relationship was established between the acidity of the heterocyclic fragment and the presence of electron donor substituents. The obtained pKa values of the compounds correlate with the calculated possible deprotonation centers of the molecule. It was found that determining the acidity constants of substances is useful for clarifying the mechanisms of their transformations. The possibility of establishing a relationship between the structure of the compound, pKa, and probable biological activity was shown.

Ultra-Narrowband Circularly Polarized Luminescence from Multiple 1,4-Azaborine-Embedded Helical Nanographenes.

In this manuscript we present a strategy to achieve ultranarrowband circularly polarized luminescence (CPL) from multiple 1,4-azaborine-embedded helical nanographenes. The impact of number and position of boron and nitrogen atoms in the rigid core of the molecule on optical properties─including absorption and emission maxima, photoluminescence quantum yield, Stokes shift, excited singlet-triplet energy gap and full width at half-maximum (fwhm) for CPL and fluorescence─was investigated. The molecules reported here exhibits ultranarrowband fluorescence (fwhm 16-17.5 nm in toluene) and CPL (fwhm 18-19 nm in toluene). To the best of our knowledge, this is among the narrowest CPL for any organic molecule reported to date. Quantum chemical calculations, including computed CPL spectra involving vibronic contributions, provide valuable insights for future molecular design aimed at achieving narrowband CPL.

The Study of Reaction of Hexafluoro‐1,4‐Napthoquinone With Substituted 5‐Aminopyrazoles

ABSTRACTFor the first time, the interaction of perfluoro‐1,4‐naphthoquinone with various 5‐aminopyrazoles was investigated. It was shown that three types of products can be obtained depending on the structure of starting aminopyrazole. For all examples, the substitution of one fluorine atom in quinone moiety was observed. Wherein, in most cases, the starting aminopyrazoles act as a C‐nucleophile leading to 2‐(5‐aminopyrazol‐4‐yl)‐3,5,6,7,8‐pentafluoronaphthalene‐1,4‐diones. At the same time substrates unsubstituted at ring nitrogen atom regiospecifically react at aminogroup resulting in the formation of 2,5,6,7,8‐pentafluoro‐3‐((pyrazol‐5‐yl)amino)naphthalene‐1,4‐diones. Besides that, the absence of steric hindrance in the pyrazole unit allowed us to direct the process at nitrogen atom in Position 2 and synthesize zwitter‐ionic 3‐(5‐aminopyrazol‐2‐ium‐2‐yl)‐5,6,7,8‐tetrafluoro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐olates. The structures of two types of obtained products were confirmed by x‐ray analysis.

2‐Ethenyl Imidazolium Salts: Synthesis, Characterization, and Evaluation as Potential Chemotherapeutics

AbstractAs candidates for intravesical exfoliants to treat bladder cancer, we have prepared fourteen new imidazolium compounds substituted at the 2 position. These compounds were produced by use of the Knoevenagel reaction between a series of aryl aldehydes and 2‐methyl imidazolium salts. Two azolium systems were examined (benzimidazole and 4,5‐dichloroimidazole) and each of these heterocycles are substituted off the nitrogen atom positions with naphthalen‐2‐ylmethyl groups. NMR spectroscopy confirms formation of the carbon‐carbon double bond, and X‐ray crystallography confirmed that the alkenes adopt the E conformation. These new imidazolium salts were evaluated for their chemotherapeutic activity using the NCI‐60 Human Tumor Cell Line Screen, and we observed that the benzimidazolium systems were more toxic than the dichloroimidazolium systems, and that the methyl phenol ether or dimethyl aniline modified compounds showed the highest activities.

Role of Pyridine Nitrogen Position on the Moisture Sensitivity of Organic Emitters.

Moisture-sensitive fluorescent emitters are a class of smart materials that can change their emission behavior upon exposure to water. In this study, we have synthesized two highly fluorescent organic emitters, 4BPy-PTA and 2BPy-PTA, and showed how moisture sensitivity can be enhanced by molecular design modification. Owing to the different nitrogen atom positions in the acceptor units, the emitters show different degrees of moisture sensitivity. Upon moisture exposure, both emitters change their emission color from greenish-yellow to blue, but a larger shift was witnessed in 4BPy-PTA (81 nm) than in 2BPy-PTA (68 nm). Moisture exposure enhances the photoluminescence quantum yield (PLQY) of 4BPy-PTA from 37 to 48%, whereas it suppresses the PLQY of 2BPy-PTA from 59 to 15%. A shorter moisture sensing time, large emission color shift, and enhanced PLQY make 4BPy-PTA a better moisture-sensitive material than 2BPy-PTA. Interestingly, the emission colors of the emitters can be completely regained by heating and partially by applying mechanical force to the moisture-exposed solids. In addition, these emitters also show mechanochromic luminescence behavior with a completely reversible emission color switch between blue and green.

Synthesis of Piperazine-containing Derivatives and their Antimicrobial, Antimycobacterial, Antimalarial and Antioxidant Activities

Background: One of the most crucial heterocycles is piperazine for the creation of novel medication candidates with a variety of medicinal applications. The piperazine moiety is a cyclic compound with four carbon atoms and two nitrogen atoms in positions 1 and 4. Objective: The objective of this studty is the development of 1-((3,4-dimethoxyphenyl) (substitutedphenyl) substituted -piperazine (A1-A10) analogs via the one-pot synthesis method and evaluation for their preliminary antibacterial, antifungal, antimycobacterial, antioxidant, and antimalarial activity. Methods: Desired piperazine derivatives were obtained in a single step reaction using piperazine, aldehydes, and boronic acid derivatives. The structures of all newly synthesized compounds have been established based on analytical and spectral data. An in silico molecular docking study was carried out for the series. Results: The spectral data using IR, 1 H NMR, and 13C NMR and mass spectra confirmed the structure of the synthesized compounds. Compounds A6 and A10 were found to be the most promising agents for antimalarial activity. A1-A10 showed a higher IC50 value and found less antioxidant activity. Some of the compounds showed higher potency when compared to the standard drugs in this antimicrobial study. Conclusion: The structure-activity study showed that changes in substituents either on aldehyde, piperazine, or boronic acid derivatives can lead to potential active compounds. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment of microbial, tubercular and malarial diseases.

Imino(dialkylamino)isoindolines: Structures and dynamic behavior

In 1956, Elvidge and coworkers investigated the synthesis of a series of isoindoline compounds derived from phthalonitrile. They produced a series of secondary amine-modified isoindolines known as the imino(dialkylamino)isoindolines, and in this report, we revisit this chemistry. In addition to confirming the previously observed reactivity, we structurally characterized three examples and observed a double bond character between the isoindoline carbon atom and the secondary nitrogen atom position. This results in a rotational barrier about this bond, which we observed by NMR spectroscopy and probed using computational methods. The barriers are comparable to those seen in bis-substituted amides.

Porphyrin photosensitizers compatible with both aqueous and non-aqueous conditions: Acid dependent spectral, solubility and photocatalytic properties of meso-tetra(pyridyl)porphyrins

The aerobic photooxidation of 1,3-diphenylisobenzofuran (DPBF) as a specific singlet oxygen quencher was studied in the presence of meso-tetra(aryl)porphyrins (aryl = 2-pyridyl, 3-pyridyl and 4-pyridyl) and their diprotonated and hexaprotonated derivatives to investigate the influence of the position of pyridine nitrogen atom, solvent, core protonation (with HCl or dichloroacetic acid) and full protonation of the porphyrins on their photocatalytic activity and photooxidative stability. The pseudo-first order rate constants (kobs) for the oxidation of DPBF with singlet oxygen were determined to compare the relative activity of the photosensitizers. 1,4-benzoquinone as a scavenger of superoxide anion radical provided evidence for the absence of this species in these photocatalytic systems. The singlet oxygen quantum yields (φΔ) of the porphyrin photosensitizers were estimated by determining the initial rate constants for the oxidation of DPBF. H4T(2-Py)P(Cl)2 and H4T(2-Py)P(CHCl2COO)2 were the most efficient photosensitizers of the series of the meso-tetra(2-, 3- or 4-pyridyl)porphyrins and the protonated derivatives.

Novel 6-alkyl-bridged 4-arylalkylpiperazin-1-yl derivatives of azepino[4,3-b]indol-1(2H)-one as potent BChE-selective inhibitors showing protective effects against neurodegenerative insults

Due to the putative role of butyrylcholinesterase (BChE) in regulation of acetylcholine levels and functions in the late stages of the Alzheimer's disease (AD), the potential of selective inhibitors (BChEIs) has been envisaged as an alternative to administration of acetylcholinesterase inhibitors (AChEIs). Starting from our recent findings, herein the synthesis and in vitro evaluation of cholinesterase (ChE) inhibition of a novel series of some twenty 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one derivatives, bearing at the indole nitrogen diverse alkyl-bridged 4-arylalkylpiperazin-1-yl chains, are reported. The length of the spacers, as well as the type of arylalkyl group affected the enzyme inhibition potency and BChE/AChE selectivity. Two compounds, namely 14c (IC50 = 163 nM) and 14d (IC50 = 65 nM), bearing at the nitrogen atom in position 6 a n-pentyl- or n-heptyl-bridged 4-phenethylpiperazin-1-yl chains, respectively, proved to be highly potent mixed-type inhibitors of both equine and human BChE isoforms, showing more than two order magnitude of selectivity over AChE. The study of binding kinetics through surface plasmon resonance (SPR) highlighted differences in their BChE residence times (8 and 47 s for 14c and 14d, respectively). Moreover, 14c and 14d proved to hit other mechanisms known to trigger neurodegeneration underlying AD and other CNS disorders. Unlike 14c, compound 14d proved also capable of inhibiting by more than 60% the in vitro self-induced aggregation of neurotoxic amyloid-β (Aβ) peptide at 100 μM concentration. On the other hand, 14c was slightly better than 14d in counteracting, at 1 and 10 μM concentration, glutamate excitotoxicity, due to over-excitation of NMDA receptors, and hydrogen peroxide-induced oxidative stress assessed in neuroblastoma cell line SH-SY5Y. This paper is dedicated to Prof. Marcello Ferappi, former dean of the Faculty of Pharmacy of the University of Bari, in the occasion of his 90th birthday.

Synthesis, spectroscopic and biological characterizations of platinum(IV), ruthenium(III) and iridium(III) theophylline complexes

This study used micro-analyses, (FTIR, UV-Vis) spectra, magnetic, thermogravimetric, X-ray powder diffraction (XRD) patterns, and transmittance electron microscopy (TEM) techniques to characterize three synthesized theophylline (TPH) complexes with ruthenium(III), platinum(IV), and iridium(III) metal ions. The metal ions indicated above were found to align with the TPH drug chelate as a mono-dentate ligand via the deprotonated NH group at the nitrogen atom position N7, as verified by FTIR measurements. Additionally, the complexes conductivity and magnetic susceptibility were examined. The octahedral geometry for the synthesized complexes was proposed by the current data. Except for the iridium(III) complex, which has a non-electrolytic nature due to the presence of a chlorine atom inside the chelation sphere, the molar conductivity of the complexes in DMSO solution was electrolyte in nature. Theophylline complexes with a (metal: ligand) stoichiometry of 1:2 were produced. The TPH complexes have also been tested in vitro against G(+) bacteria (Bacillus subtilis and Staphylococcus Aureus) and G(-) bacteria (Pseudomonas aeruginosa and Escherichia coli) to evaluate their antibacterial efficacy. Human breast and liver cancer cell lines were used as a test for the TPH complexes in vitro anti-cancer properties.
 KEY WORDS: Theophylline, Metal ions, Chelation, Octahedral, Spectral analysis, Nano-particles, Biological evaluation
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 725-738. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.14

Encoding Genetic and Structural Information in DNA Using Electric Field Gradients and Nuclear Spins

Nuclear electric resonance (NER) offers a method of controlling nuclear spins using electric field gradients (EFGs), which is a critical concept in quantum computing. In this study, we focus on nitrogen atoms in DNA, which have a nuclear spin of 1 and are influenced by EFGs. Utilizing molecular dynamics simulations, quantum chemical computations, and theoretical analyses, we studied the characteristics of EFGs in the context of DNA. Our results show that the orientation patterns of the EFGs at the positions of nitrogen atoms in DNA bases vary with different types of bases and nitrogen atom sites. Consequently, the genetic and structural information of DNA is encoded into the direction of the nitrogen nuclear spins. Furthermore, the interaction and evolution of these nitrogen nuclear spins with surrounding nuclear spins suggest the potential for quantum computing of genetic information. Our findings not only provide new insights into quantum phenomena in biological systems but also lay the groundwork for expanding the theoretical foundations of DNA quantum computing and offer innovative approaches for the design of future biocompatible quantum computers.

Impact of the position of nitrogen atom on the liquid crystal, optical and multi-stimuli response behaviors of rod-like mesogens containing multiple functional building blocks

Two novel rod-like mesogens containing one cyanostyrene, one pyridine and one pyrene as π-conjugate rigid core were designed and synthesized by Suzuki coupling and Knoevenagel reactions. The effect of the position of nitrogen-atom on the thermodynamic behavior, liquid crystalline self-assembly, optical behavior, mechanochromism behavior and acidochromism behavior was investigated. The rod-like mesogen in which the nitrogen atom is adjacent to the pyrene displays a phase transition from smectic A to smectic C by increasing temperature, whereas the other rod-like mesogen can only self-assemble into smectic C phase. This difference in mesophase transition behavior might be attributed to the position of nitrogen-atom which induces the change in molecular configuration. Both mesogens exhibit positive solvatochromism and high fluorescence in both solution state and aggregated state which might be attributed to the intramolecular charge transfer and twisted molecular configurations, respectively. Reversible mechanochromism behavior due to changes in molecular stacking and acidochromism behavior due to protonation and deprotonation were also achieved. These multi-stimuli responsive behaviors of the designed rod-like mesogens demonstrate potential applications in the field of multifunctional materials.

A Comparative Study of Pt/Al0.72Sc0.28N/Pt-Based Thin-Film Metal-Ferroelectric-Metal Capacitors on GaN and Si Substrates.

AlxSc1-xN is a nitride-ferroelectric compatible with both CMOS and GaN technology. The origin of ferroelectricity in these ternary nitrides relies on the full inversion of nitrogen atom positions, which is a significantly different structural mechanism than conventional perovskites. Therefore, its ferroelectric characteristics exhibit a high remanent polarization and a tunable coercive field but suffer heavily from leakage currents during the switching event. In this article, we studied epitaxially grown Al0.72Sc0.28N thin films on epitaxial Pt electrode layers deposited on GaN/Al2O3 substrates. The results are compared both structurally and electrically with similar systems on SiO2/Si substrates. Our X-ray diffraction analysis showed that Al0.72Sc0.28N/epi-Pt/GaN is always a complete epitaxial stack without any significant strain gradient. Electrically, this system has an overall lower leakage current and coercive field compared to directly grown, highly crystalline, strained epitaxial Al0.72Sc0.28N/GaN, despite having a lower crystalline quality of the ferroelectric layer. In addition, decreasing the epi-Pt thickness from 100 to 10 nm resulted in further improvement of the leakage profile, which we attribute to a decrease in surface roughness in the thinner Pt. In contrast, the dominant factor of leakage in a fiber-textured system on Si substrates is the Pt(111) texture. Finally, with the combination of in-plane X-ray diffraction and high-resolution scanning transmission electron microscopy, we have demonstrated an all-epitaxial 20 nm Al0.72Sc0.28N/Pt/GaN MFM stack with a sharp interface thickness of less than 1 nm.

Retraction Note to: The Effects of Percent and Position of Nitrogen Atoms on Electronic and Thermoelectric Properties of Graphene Nanoribbons

Retraction Note to: The Effects of Percent and Position of Nitrogen Atoms on Electronic and Thermoelectric Properties of Graphene Nanoribbons

Carboline Regioisomers Based on Unified Synthetic Approaches

AbstractCarbolines are a prominent class of tricyclic alkaloids omnipresent in natural products and bioactive compounds. Four different carboline regioisomers are known (α‐, β‐, γ‐, and δ‐carbolines), which can be classified according to the nitrogen atom position inside the pyridine ring. As an emerging structural motif in drug discovery, a multitude of synthetic methods have been established for the construction of carboline frameworks, which in general requires customized approaches for the assembly of each regioisomer. Distinguishingly, their frameworks are also accessible from unified approaches, which are capable of generating multiple regioisomers, thus suitable for introducing diversity in isomeric carbolines. In this review, the construction of isomeric carbolines based on unified synthetic approaches is summarized.

Structure-Selectivity Relationship Prediction of Tau Imaging Tracers Using Machine Learning-Assisted QSAR Models and Interaction Fingerprint Map.

Protein aggregates composed of tau fibrils are major pathologic findings in different tauopathies. An ideal agent for imaging tau fibrils must be highly selective. The molecular basis for the binding of current available compounds to tau aggregates is not well understood. Herein, we provide insights into previously studied positron emission tomography tracers using various computational methods, including machine learning-based quantitative structure-activity relationship (QSAR) classification, docking, and molecular dynamics (MD) simulations to investigate the structural basis of selective tau aggregate binding for potential compounds. The QSAR classification model based on the Random Forest algorithm with an accuracy of 96.6% for the selective and 97.6% for the nonselective class of compounds revealed essential selective moieties. The combination of molecular docking, MD simulations, and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) binding free-energy calculation showed superior binding energy of ligand 63 toward tau and PHF6, a key hexapeptide in tau aggregation, as the most selective compound in the data set. Dissecting the binding properties of ligand 63 and ligand 8 (the least selective compound) within tau and Aβ structures confirmed that these two compounds favor different binding sites of tau; however, the preferential binding site in Aβ was similar for both with lower binding energies calculated for ligand 8. Results revealed that the number of N-heterocycles, the position of nitrogen atoms, and the presence of tertiary amine are important components of selective binding moieties, and they should be maintained in molecules for selective binding to tau aggregates. The predicted structure-selectivity relationship will facilitate the rational design and further development of selective tau imaging agents.