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Here we report our investigation of 1‐bromo‐3,5,7‐triphenyladamantane (1) and the elucidation of polymorphic crystals (1 A and 1 B) using single crystal X‐ray diffraction. In the monoclinic crystal system of 1 A (P21/n), we observed CH–π interactions, while Br⋅⋅⋅Br interactions are absent. Conversely, the Br⋅⋅⋅Br interactions are an apparent factor in the formation of the monoclinic crystal system of 1 B (R3‾ ${\bar{3}}$). We compare our findings with 1,3,5,7‐tetraphenyladamantane (2), characterized by numerous CH–π interactions in the solid. Computational analyses were employed to investigate the interactions within the characteristic dimers present in the unit cells of 1 A and 1 B, including visualization of noncovalent interactions and the use of the atoms‐in‐molecules approach as well as MO analyses. These support the notion of London dispersion (LD) dimer‐dimer interactions in 1 A between the phenyl moieties, whereas 1 B exhibits additional dimer‐dimer Br⋅⋅⋅Br contacts. In contrast, the crystals of 2 are exclusively held together by CH–π stacking LD interactions, a feature absent in the polymorphs of 1. Both polymorphic forms of 1 emit white light when subjected to 900 nm continuous wave laser irradiation, displaying a subtle blue shift compared to 2. The absence of CH–π stacking interactions between the dimers of 1 causes a small red‐shift in the emission spectrum. [ABSTRACT FROM AUTHOR]

We showcase herein organic crystalline solid solutions (CSSs) based on the simplest polycyclic aromatic hydrocarbon (PAH) scaffold, naphthalene, stabilized by dispersion forces induced by adamantane substitution. High thermal stability of the host and guest molecules synthesized by cross‐coupling of dibromonaphthalene derivatives and 4‐(1‐adamantyl)phenyl boronic ester enabled formation of crystals by sublimation. We could generate binary monocrystalline solid solution systems proven by X‐ray crystallography, the first system of designed CSSs stabilized exclusively via dispersion forces with structural evidence. These observations are additionally supported by lattice energy calculations and spectroscopic examinations. For the generation of CSSs, it is of utmost importance that the host and guest molecules have similar lattice energies and spatial compatibility. We anticipate that the thermostable organic CSS design demonstrated herein would be beneficial for functional materials and further investigation towards materials with unique properties. [ABSTRACT FROM AUTHOR]

Tetraspanin CD81 is a transmembrane protein used as a co-receptor by different viruses and implicated in some cancer and inflammatory diseases. The design of therapeutic small molecules targeting CD81 lags behind monoclonal antibodies and peptides but different synthetic and natural products binding to CD81 have been identified. We have investigated the interaction between synthetic compounds and CD81, considering both the cholesterol-bound full-length receptor and a truncated protein corresponding to the large extracellular loop (LEL) of the tetraspanin. They represent the closed and open conformations of the protein, respectively. Stable complexes were characterized with bi-aryl compounds (notably the quinolinone-benzothiazole 6) and atypical molecules bearing a 1-amino-boraadamantane scaffold well adapted to interact with CD81 (5a-d). In each case, the mode of binding to CD81 was analyzed, the binding sites identified and the molecular contacts determined. The narrow intra-LEL binding site of CD81 can accommodate the elongated bi-aryl 6 but not a series of isosteric compounds with a bis(bicyclic) scaffold. The bora-adamantane derivatives appeared to bind well to CD81, but essentially to the external surface of the protein loop. The binding selectivity of the compounds was assessed comparing binding to the LEL of tetraspanins CD81, CD9 and Tspan15. A net preference for CD81 over CD9 was evidenced, but the LEL of Tspan15 also provided a suitable binding site for the compounds, notably for the bora-adamantane derivatives. This work provides an aid to the identification and design of tetraspanin-binding small molecules, underlining the distinct behavior of the open and closed conformation of the protein for drug binding. [ABSTRACT FROM AUTHOR]

Reactions of 3-(bromomethyl)-5,7-dimethyl-2-oxaadamantan-1-ol with various nucleophiles afforded a number of new 2-oxaadamantane derivatives. The synthesized compounds may be considered as starting materials for targeted synthesis of potentially biologically active compounds. [ABSTRACT FROM AUTHOR]

We report the synthesis, spectroscopic properties, and anti-proliferative efficacy of the adamantane-linked 1,2,4-triazole derivative 5-(adamantan-1-yl)-4-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione. Crystal packing and intermolecular interactions have been quantified using Hirshfeld surfaces and two-dimensional fingerprint plots. ADMET characteristics, bioavailability, and drug-likeness define the compound's bioactivity. The gastrointestinal absorption is anticipated to be high, and the projected bioavailability score is 0.55. The topological polar surface area and iLOGP, XLOGP, WLOGP, and MLOGP lipophilicity parameters have been calculated to be 65.70 Å2, 3.24, 4.74, 5.05, and 4.07, respectively. To investigate 5A4ClT's EGFR inhibition and its use in the treatment of non-small cell lung cancer, Autodock Vina was used to dock it with the crystal structure of the EGFR kinase domain protein. The title chemical hydrophobically interacts with the receptor residues LEU718, VAL726, ALA743, GLU762, THR790, LEU792, MET793, GLY796, ARG841, ASN842, and LEU844 and forms hydrogen bonds with ASP855 and THR854 with an affinity of −8.3 kcal/mol. Toxicity end points and comparison with NSCLC drugs yielded promising findings. 120 ns molecular dynamics simulations confirmed the ligand's dynamic stability in the target protein's binding pocket. This research lays the groundwork for future in vivo investigations of 5A4ClT as a non-small cell lung cancer therapy. [ABSTRACT FROM AUTHOR]

Exploiting triplet excitons in TADF sensitizers and hot‐exciton emitters has attracted considerable attention and interest in recent studies on the design and development of blue OLEDs. The structural and optical property relationship of adamantane (Ad) core appended with four different strengths of donor and seven acceptor units were investigated using DFT and TD‐DFT methods. The theoretical studies revealed that increased donor and acceptor strength on adamantane building block leads to: (i) a decrease in ionization potentials and an increase in electron affinities, (ii) a decrease in singlet energies (ES) and the S1‐T1 energy gaps (ΔEST); (iii) decreased SOC magnitudes between S1‐T1 states; (iv) increased RISC rate from the Tn to S1 states, demonstrating an increased tendency for upconversion of triplet excitons from the Tn to S1 state. In addition, low exchange energy causes excited state characteristics of molecules to shift from HLCT to CT nature in the S1 state. In contrast, the T1 states retain their LE character, resulting in higher triplet energies (ET). The adamantane molecular systems appended with P‐DMAC‐Donor‐Ad‐P‐DMB and Donor‐Ad‐P‐BODIPY based triads exhibit promising TADF sensitizer and hot‐exciton characteristics to find application as potential candidates for blue OLEDs when compared to experimentally reported conventional host. [ABSTRACT FROM AUTHOR]

Crystallizing molecules with long flexible chains is a challenge, making it difficult to perform X‐ray crystallography. Chaperones can assist in the crystallization of compounds that do not crystallize by themselves by producing solvate crystals that contain the analyte in their three‐dimensional lattices. Among the most versatile chaperones for liquid analytes are tetraaryladamantanes (TAAs), but the size of the compounds that can be encapsulated is limited, and attempts to surpass this limit with known TAAs were unsuccessful. Here we report that 1,3,5,7‐tetrakis(2‐fluoro‐4‐methoxyphenyl)adamantane (TFM) is a crystallization chaperone for acyclic molecules up to the molecular weight of phytyl acetate (338 g/mol). Encapsulation of such a large acyclic compound was achieved when the analyte was esterified and when a two‐step temperature protocol was used for crystallization. Exploratory work indicates that a drop to −20 °C allows for encapsulation of squalene (Mr 411 g/mol), albeit with positional disorder of the analyte. Our X‐ray crystal structures of solvates with flexible analytes shed light on how crystalline order can be imposed on large acyclic analytes. The new, fluorinated TAA gives access to crystal structures that were inaccessible thus far. [ABSTRACT FROM AUTHOR]

Polar crystalline materials, a subset of the non‐centrosymmetric materials, are highly sought after. Their symmetry properties make them pyroelectric and also piezoelectric and capable of second‐harmonic generation (SHG). For SHG and piezoelectric applications, metal oxides are commonly used. The advantages of oxides are durability and hardness – downsides are the need for high‐temperature synthesis/processing and often the need to include toxic metals. Organic polar crystals, on the other hand, can avoid toxic metals and can be amenable to solution‐state processing. While the vast majority of polar organic molecules crystallize in non‐polar space groups, we found that both 7‐chloro‐1,3,5‐triazaadamantane, for short Cl‐TAA, and also the related Br‐TAA (but not I‐TAA) form polar crystals in the space group R3m, easily obtained from dichloromethane solution. Measurements confirm piezoelectric and SHG properties for Cl‐TAA and Br‐TAA. When the two species are crystallized together, solid solutions form, suggesting that properties of future materials can be tuned continuously. [ABSTRACT FROM AUTHOR]

In this work, 4-bromobenzyl(Z)-N'-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate (4BAPC), an adamantane-isothiourea derivative, was studied through density functional theory (DFT) at the M06-2X/6 − 311 + G(2df,2p) level of theory, where its structural, vibrational, and quantum-chemical properties were comprehensively described. The analysis of the IR and Raman frequencies, with the help of potential energy distribution (PED) calculation, allowed the assignment of several characteristic vibrations that may be used in the identification of other adamantane-isothiourea derivatives. Solvation-free energy (SFE) calculations in water, ethanol, acetone, and chloroform were carried out, where acetone and chloroform showed the most negative values, −23.34 and −23.33 kcal/mol, respectively, suggesting that these two solvents better solubilize 4BAPC. Also, the SFE value in water, −10.49 kcal/mol, indicates good solubility in an aqueous medium. FMOs, MEP, ALIE surfaces, and Fukui indices calculations allowed to identify that the most reactive sites of 4BAPC comprise the aromatic rings and piperazine moiety. Acetylcholinesterase (AChE) inhibition capacity presented by 4BAPC was evaluated through molecular docking and molecular dynamics (MD) calculations. Docking binding affinity and MMPBSA binding energy showed, respectively, values of −9.2 and −29.954 kcal/mol, which indicates strong evidence for the AChE inhibitory potential by 4BAPC. [ABSTRACT FROM AUTHOR]

We report channel confinement and separation properties of an adaptive supramolecular framework based on an adamantane tecton. Specifically, the framework is self-assembled from a tetraaryl-substituted adamantane tecton (i.e., 1,3,5,7-tetrakis(4-bromophenyl)adamantane) via van der Waals contacts, phenyl embraces and halogen bonds. The adamantane framework displays modular channels that confine aromatic petrochemicals and chloroform, and enables separation of toluene from benzene via crystallization. [ABSTRACT FROM AUTHOR]

Methods have been developed for the synthesis of N-[2-(adamantan-2-yl)ethyl]-N′-R-ureas and -thioureas in 36–87% yields by the reaction of 2-(adamantan-2-yl)ethanamine with aromatic isocyanates and isothiocyanates. The displacement of the ethylene bridge from position 1 to position 2 of the adamantane fragment has been found to exert no significant effect on the logP values and melting points of the corresponding ureas. [ABSTRACT FROM AUTHOR]

[Display omitted] Aluminate ionic liquid [Et 3 NH]+[Al 2 Cl 7 ]− was found to be an effective catalyst for the reactions of haloadamantanes with trimethylsilyl azide to produce the corresponding azido- adamantanes in 92–98% yields. Using 'click chemistry', the thus obtained azidoadamantanes were reacted with terminal alkynes under thermal or microwave conditions to cleanly afford the expected 1,4-disubstituted 1,2,3-triazoles some of which were new. [ABSTRACT FROM AUTHOR]

A possibility of using the reductive intramolecular Heck–Matsuda reaction of a sterically hindered substituted allylic ether in the synthesis of 3-(adamantan-1-yl)-3-methyl-2,3-dihydrobenzofuran was demonstrated for the first time. [ABSTRACT FROM AUTHOR]

A series of new (thio)semicarbazones containing adamantane and 3,7-dimethyloctyl fragments was synthesized. The configuration of imine bond was proposed based on the characteristic signals of 1Н and 13С NMR spectra simulated by quantum-chemical calculations. [ABSTRACT FROM AUTHOR]

New imidazolidine-2,4,5-triones with norabietic, nordehydroabietic, and adamantane substituents were synthesized by reacting oxalyl chloride and the corresponding ureas, providing good yields. Bioisosteric replacement of the ureide group with a parabanic acid fragment made it possible to increase the solubility of compounds and conduct biological studies. The compounds inhibit the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 in submicromolar concentrations. Cytotoxic concentrations were also studied on the glioblastoma cell line SNB19. [ABSTRACT FROM AUTHOR]

Series of 1,3-disubstituted ureas and diadamantyl disubstituted diureas with fluorinated and chlorinated adamantane residues were shown to inhibit human soluble epoxide hydrolase (sEH) with inhibition potency ranging from 40 pM to 9.2 nM. The measured IC50 values for some molecules were below the accuracy limit of the existing in vitro assays. Such an increase in activity was achieved by minimal structural modifications to the molecules of known inhibitors, including 4-[trans-4-(1-adamantylcarbamoylamino)cyclohexyl]oxybenzoic acid. For the chlorinated homologue of the latter the sharp jump in inhibitory activity can be (according to molecular dynamics data) the result of interactions – Cl-π interaction. Considering the extremely high inhibitory activity, acceptable solubility and partial blockage of metabolically sensitive centres in their structures, some compounds are of interest for further in vivo biotesting. [ABSTRACT FROM AUTHOR]

A series of N,N′-disubstituted ureas and bis-ureas were synthesized in 36–85% yields by the reaction 3-bromoadamantan-1-yl isocyanate with α,ω-alkanediamines, fluorinated anilines, and trans-4-[(4-aminocyclo-hexyl)oxy]benzoic acid. The hydrolysis of 3-bromoadamant-1-yl isocyanate in the presence of a catalytic amount of DBU gave 60% of symmetrical N,N′-bis(3-bromoadamantan-1-yl)urea. The synthesized compounds are promising as inhibitors of human soluble epoxide hydrolase (hsEH). [ABSTRACT FROM AUTHOR]

The Chan–Lam reaction conditions were optimized for the synthesis of N-aryl derivatives of adamantane-containing amines. A number of adamantane-containing amines and diamines with different steric hindrances at the primary amino groups were reacted with p-tolylboronic acid under the optimized conditions [0.1 M solution of amine in MeCN, p-tolylboronic acid (2 equiv), DBU (2 equiv), copper(II) acetate (20 mol %), 25°C, 24 h]. The reactivity of the amines was found to strongly depend on their structure, and the maximum yield of the target products reached 74% from the monoamines and 66% from the diamines. [ABSTRACT FROM AUTHOR]

This review summarizes achievements in the synthesis of 1,2-disubstituted adamantane derivatives by the construction of the tricyclic framework either by total synthesis or by ring expansion/contraction reactions of corresponding adamantane homologues. It is intended to complement reviews focusing on the preparation of 1,2-disubstituted derivatives by C–H functionalization methods. [ABSTRACT FROM AUTHOR]

A mixture of a nucleophilic substitution product and its isomeric azide resulting from [3,3]-sigmatropic rearrangement was obtained as a result of the reaction of hindered bromides of the adamantane series with sodium azide. Epoxidation reactions of allylic azides of the adamantane series were investigated. The reduction of the syntesized trans-2-(adamantan-1-yl)-3-(azidomethyl)oxirane with lithium alumohydride gave (S*)-(adamantan-1-yl)[(S*)-aziridin-2-yl]methanol. Under heating with HCl, the latter underwent aziridine ring opening to form (1S*,2R*)-1-(adamantan-1-yl)-3-chloro-1-hydroxypropan-2-aminium chloride. [ABSTRACT FROM AUTHOR]

A convenient method has been proposed for the preparation of new derivatives of adamantine-based drugs, such as memantine and rimantadine. The synthesis was performed by functionalization of amino-group of memantine and rimantadine by ipso-substitution of cyano-group at C5 position of 1,2,4-triazine scaffold with the corresponding aminoadamantane moieties with subsequent aza-Diels–Alder transformation of 1,2,4-triazine cycle into pyridine one in some cases. [ABSTRACT FROM AUTHOR]

The reaction of adamantan-1-ol with lower alcohols (methanol, ethanol) in the presence of water and an equimolar amount of CuBr2 (with respect to adamantan-1-ol) at 220°C for 4 h gives adamantane in a high yield. (E)-(Prop-1-en-1-yl)adamantane was obtained in a high yield from adamantan-1-ol and isopropanol under similar conditions but in the absence of water. [ABSTRACT FROM AUTHOR]

N-(Het)arylation of adamantane-containing amines with halonaphthalenes and haloquinolines catalyzed by either CuI or copper nanoparticles with an average size of 25 nm in the presence of 2-isobutyrylcyclohexanone, rac-BINOL, and l-proline as a ligand and Cs2CO3 as a base in DMSO at 110 °C was studied. The reactions proceed smoothly with 2-iodonaphthalene and 6-iodoquinoline, the possibility of successful reactions with 6- and 3-bromoquinolines was also shown. In the case of 1-bromonaphthalene, 5- and 8-bromoquinolines, only Pd-catalyzed amination can provide the high yields of the products. An alternative possibility of C(sp2)—N bond formation was studied employing the Chan—Lam reaction with of 2-naphthaleneboronic acid and pinacolates of 6- and 3-quinolineboronic acids. [ABSTRACT FROM AUTHOR]

Supramolecular responsive microcarriers based on chitosan microspheres were prepared and applied for nonenzymatic cell detachment. Briefly, chitosan microspheres (CSMs) were first prepared by an emulsion crosslinking approach, the surface of which was then modified with β-cyclodextrin (β-CD) by chemical grafting. Subsequently, gelatin was attached onto the surface of the CSMs via the host–guest interaction between β-CD groups and aromatic residues in gelatin. The resultant microspheres were denoted CSM-g-CD-Gel. Due to their superior biocompatibility and gelatin niches, CSM-g-CD-Gel microspheres can be used as effective microcarriers for cell attachment and expansion. L-02, a human fetal hepatocyte line, was used to evaluate cell attachment and expansion with these microcarriers. After incubation for 48 h, the cells attached and expanded to cover the entire surface of microcarriers. Moreover, with the addition of adamantane (AD), cells can be detached from the microcarriers together with gelatin because of the competitive binding between β-CD and AD. Overall, these supramolecular responsive microcarriers could effectively support cell expansion and achieve nonenzymatic cell detachment and may be potentially reusable with a new cycle of gelatin attachment and detachment. [ABSTRACT FROM AUTHOR]

A series of three lithium silylamides Li2Me2Si(NC6H4‐2‐SR)2 (R=Me, Ph, tBu) were prepared from the reaction of the corresponding silylamines Me2Si(NH‐C6H4‐2‐SR)2 with n‐butyl lithium. X‐ray single crystal structure analyses revealed the formation of dimers [Li4{Me2Si(NC6H4‐2‐SR)2}2] with Si2N4Li4 hetero‐adamantane cores. Recrystallisation of [Li4{Me2Si(NC6H4‐2‐SMe)2}2] and [Li4{Me2Si(NC6H4‐2‐SPh)2}2] from diethyl ether led to the formation of the adducts [Li4(Et2O)2{Me2Si(NC6H4‐2‐SMe)2}2] and [Li4(Et2O){Me2Si(NC6H4‐2‐SPh)2}2]. In the case of the SMe derivative the addition of two diethyl ether molecules led to a rearrangement of the Si2N4Li4 core to give a double decker structure and in contrast the hetero adamantane structure is retained in the diethyl ether adduct of the SPh derivative. [ABSTRACT FROM AUTHOR]

The synthesis of new water-soluble N-alkylated derivatives of 1,3,5-triaza-7-phosphaadamantane is presented. Ru(PPh3)2Cl2 has been used to react with 1-(4-nitrobenzyl)-3,5-triaza-1-azonia-7-phosphaadamantane bromide (PTAR). By using elemental analysis, NMR, and IR spectroscopy, the obtained compounds were identified. The UV-visible absorption spectroscopy has been used to monitor the complexation of various transition metal cations. Studies on conductivity have been utilized to validate the complexes' stoichiometries. Using the disc diffusion method, five bacteria strains were used for the study of the antimicrobial activity of compounds 1-3. All tested pathogens, including M luteus LB 141107, were found to have strong biologic activity against the compounds tested in this study. Additionally, DPPH (2,2-diphenyl-1-picrylhydrazyl) has been tested for its ability to scavenge hydrogen peroxide and free radicals. According to our results, these compounds exhibit excellent radical scavenging properties. [ABSTRACT FROM AUTHOR]

Biomaterials with improved biological features can be obtained by conjugating glycans to nanostructured peptides. Creating peptide‐glycan chimeras requires superb chemoselectivity. We expedite access to such chimeras by merging peptide and glycan solid‐phase syntheses employing a bifunctional monosaccharide. The concept was explored in the context of the on‐resin generation of a model α(1→6)tetramannoside linked to peptides, lipids, steroids, and adamantane. Chimeras containing a β(1→6)tetraglucoside and self‐assembling peptides such as FF, FFKLVFF, and the amphiphile palmitoyl‐VVVAAAKKK were prepared in a fully automated manner. The robust synthetic protocol requires a single purification step to obtain overall yields of about 20 %. The β(1→6)tetraglucoside FFKLVFF chimera produces micelles rather than nanofibers formed by the peptide alone as judged by microscopy and circular dichroism. The peptide amphiphile‐glycan chimera forms a disperse fiber network, creating opportunities for new glycan‐based nanomaterials. [ABSTRACT FROM AUTHOR]

Urethanization of castor oil (CO), β-cyclodextrin (CD), and 1-adamantanol (AdOH) with hexamethylene diisocyanate (HDI) at a CD/AdOH molar ratio of 1:1 and various feed CO fractions produced castor oil-based polyurethane network films (CAPUs) incorporating cyclodextrin and adamantane units as host and guest components, respectively. For comparison, similar urethanization reactions were performed with CO/CD/HDI and CO/AdOH/HDI to produce network films that lacked guest or host moieties (CDPU and ADPU, respectively). The results of Fourier transform infrared spectroscopy and gel fraction measurements confirmed the formation of polyurethane networks. The glass transition temperatures, tensile strengths, and tensile moduli of the network films increased with decreasing CO fractions. All CAPU films demonstrated healing properties at room temperature; however, the CDPU and ADPU films did not. The healing efficiency also increased with decreasing CO fraction. [ABSTRACT FROM AUTHOR]

Obtaining high‐resolution structures of liquid compounds can be difficult. Encapsulating them in the lattice of a larger organic molecule acting as crystallization chaperone is one option to overcome this difficulty. Tetraaryladamantane ethers can play the role of chaperones, accommodating a range of different guest molecules in their crystals. How well‐ordered crystalline arrangements for molecules of different shape are achieved is not clear. Cases in which more than one structure is found may shed light on this phenomenon. Here, we report low‐order cubic crystal structures of 1,3,5,7‐tetrakis(2,4‐dimethoxyphenyl)adamantane (TDA) encapsulating ortho‐xylene or cyclohexane, together with better ordered structures obtained after warming the crystals to 60 °C. Evidence for cubic crystal systems was also found for limonene, hexachlorobutadiene and eucalyptol, with a transition to a triclinic system for the former two, but no transition up to 70 °C for the latter. These findings indicate that some solvate structures of TDA can readily undergo structural transitions to less solvated, better ordered systems. Crystals obtained by rapid thermal crystallization may be in kinetically trapped states, and the transition to a solvate‐free crystal system appears to have a kinetic barrier that depends strongly on the structure of the liquid guest molecules encapsulated in the lattice. [ABSTRACT FROM AUTHOR]

There is huge demand for developing guests that bind β‐CD and can conjugate multiple cargos for cellular delivery. We synthesized trioxaadamantane derivatives, which can conjugate up to three cargos per guest. 1H NMR titration and isothermal titration calorimetry revealed these guests form 1 : 1 inclusion complexes with β‐CD with association constants in the order of 103 M−1. Co‐crystallization of β‐CD with guests yielded crystals of their 1 : 1 inclusion complexes as determined by single‐crystal X‐ray diffraction. In all cases, trioxaadamantane core is buried within the hydrophobic cavity of β‐CD and three hydroxyl groups are exposed outside. We established biocompatibility using representative candidate G4 and its inclusion complex with β‐CD (β‐CD⊂G4), by MTT assay using HeLa cells. We incubated HeLa cells with rhodamine‐conjugated G4 and established cellular cargo delivery using confocal laser scanning microscopy (CLSM) and fluorescence‐activated cell sorting (FACS) analysis. For functional assay, we incubated HeLa cells with β‐CD‐inclusion complexes of G4‐derived prodrugs G6 and G7, containing one and three units of the antitumor drug (S)‐(+)‐camptothecin, respectively. Cells incubated with β‐CD⊂G7 displayed the highest internalization and uniform distribution of camptothecin. β‐CD⊂G7 showed higher cytotoxicity than G7, camptothecin, G6 and β‐CD⊂G6, affirming the efficiency of adamantoid derivatives in high‐density loading and cargo delivery. [ABSTRACT FROM AUTHOR]

There is huge demand for developing guests that bind β‐CD and can conjugate multiple cargos for cellular delivery. We synthesized trioxaadamantane derivatives, which can conjugate up to three cargos per guest. 1H NMR titration and isothermal titration calorimetry revealed these guests form 1 : 1 inclusion complexes with β‐CD with association constants in the order of 103 M−1. Co‐crystallization of β‐CD with guests yielded crystals of their 1 : 1 inclusion complexes as determined by single‐crystal X‐ray diffraction. In all cases, trioxaadamantane core is buried within the hydrophobic cavity of β‐CD and three hydroxyl groups are exposed outside. We established biocompatibility using representative candidate G4 and its inclusion complex with β‐CD (β‐CD⊂G4), by MTT assay using HeLa cells. We incubated HeLa cells with rhodamine‐conjugated G4 and established cellular cargo delivery using confocal laser scanning microscopy (CLSM) and fluorescence‐activated cell sorting (FACS) analysis. For functional assay, we incubated HeLa cells with β‐CD‐inclusion complexes of G4‐derived prodrugs G6 and G7, containing one and three units of the antitumor drug (S)‐(+)‐camptothecin, respectively. Cells incubated with β‐CD⊂G7 displayed the highest internalization and uniform distribution of camptothecin. β‐CD⊂G7 showed higher cytotoxicity than G7, camptothecin, G6 and β‐CD⊂G6, affirming the efficiency of adamantoid derivatives in high‐density loading and cargo delivery. [ABSTRACT FROM AUTHOR]

So, the optimization study gave two different acid concentration/reaction time optima for the two fully symmetrical alkylation products TBro/iTBro. Keywords: adamantane; alkylation; crystallization; Friedel-Crafts reactions; regioselectivity EN adamantane alkylation crystallization Friedel-Crafts reactions regioselectivity 2473 2482 10 07/31/23 20230817 NES 230817 Graph Introduction Adamantane is a highly symmetrical, rigid hydrocarbon that may be considered the smallest three-dimensional subunit of the diamond lattice. Here we report the formation and isolation of the regioisomer tetrakis(4-bromo-2-methoxyphenyl)adamantane (iTBro) as the main product of the Friedel-Crafts reaction under the control of a strong Brønsted acid, indicating that this is the true thermodynamic product of the Friedel-Crafts alkylation of TOA. For the heavy halogens, the I para i -halo TAAs are the predominant products of equilibria induced by treatment with the strong Brønsted acid triflic acid, whereas fluoroanisole gives predominantly the regioisomeric I ortho i -halogen product under conditions that allow for establishing isomerization equilibria. [Extracted from the article]

The molecular zirconium‐oxo cluster with 1‐adamantanecarboxylate of ideal formula [Zr6O4(OH)4(AdCA)12] (AdCA=1‐adamantanecarboxylate) has a near spherical shape with a hydrophobic "shell" of bulky rigid adamantyl groups. The use of formic acid as a modulator and a large excess of the HAdCA were found to be crucial for its reproducible synthesis and the formation of ~100‐150 μm well‐formed rhombohedral single crystals. Crystallization in the presence of formic acid leads, however, to ligand‐substitution defects (1‐2 out of 12) which were quantified by thermogravimetry and NMR. A defect‐engineering with a higher defect ratio in such oxo clusters is a promising approach aiming at extrinsic porosity. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is able to hide within host cells to escape immune clearance and antibiotic action, causing life‐threatening infections. To boost the therapeutic efficacy of antibiotics, new intracellular delivery approaches are urgently needed. Herein, by rational design of an adamantane (Ada)‐containing antibiotic‐peptide precursor Ada‐Gly‐Tyr‐Val‐Ala‐Asp‐Cys(StBu)‐Lys(Ciprofloxacin)‐CBT (Cip‐CBT‐Ada), we propose a strategy of tandem guest‐host‐receptor recognitions to precisely guide ciprofloxacin to eliminate intracellular S. aureus. Via guest‐host recognition, Cip‐CBT‐Ada is decorated with a β‐cyclodextrin‐heptamannoside (CD‐M) derivative to yield Cip‐CBT‐Ada/CD‐M, which is able to target mannose receptor‐overexpressing macrophages via multivalent ligand‐receptor recognition. After uptake, Cip‐CBT‐Ada/CD‐M undergoes caspase‐1 (an overexpressed enzyme during S. aureus infection)‐initiated CBT‐Cys click reaction to self‐assemble into ciprofloxacin nanoparticle Nano‐Cip. In vitro and in vivo experiments demonstrate that, compared with ciprofloxacin or Cip‐CBT‐Ada, Cip‐CBT‐Ada/CD‐M shows superior intracellular bacteria elimination and inflammation alleviation efficiency in S. aureus‐infected RAW264.7 cells and mouse infection models, respectively. This work provides a supramolecular platform of tandem guest‐host‐receptor recognitions to precisely guide antibiotics to eliminate intracellular S. aureus infection efficiently. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is able to hide within host cells to escape immune clearance and antibiotic action, causing life‐threatening infections. To boost the therapeutic efficacy of antibiotics, new intracellular delivery approaches are urgently needed. Herein, by rational design of an adamantane (Ada)‐containing antibiotic‐peptide precursor Ada‐Gly‐Tyr‐Val‐Ala‐Asp‐Cys(StBu)‐Lys(Ciprofloxacin)‐CBT (Cip‐CBT‐Ada), we propose a strategy of tandem guest‐host‐receptor recognitions to precisely guide ciprofloxacin to eliminate intracellular S. aureus. Via guest‐host recognition, Cip‐CBT‐Ada is decorated with a β‐cyclodextrin‐heptamannoside (CD‐M) derivative to yield Cip‐CBT‐Ada/CD‐M, which is able to target mannose receptor‐overexpressing macrophages via multivalent ligand‐receptor recognition. After uptake, Cip‐CBT‐Ada/CD‐M undergoes caspase‐1 (an overexpressed enzyme during S. aureus infection)‐initiated CBT‐Cys click reaction to self‐assemble into ciprofloxacin nanoparticle Nano‐Cip. In vitro and in vivo experiments demonstrate that, compared with ciprofloxacin or Cip‐CBT‐Ada, Cip‐CBT‐Ada/CD‐M shows superior intracellular bacteria elimination and inflammation alleviation efficiency in S. aureus‐infected RAW264.7 cells and mouse infection models, respectively. This work provides a supramolecular platform of tandem guest‐host‐receptor recognitions to precisely guide antibiotics to eliminate intracellular S. aureus infection efficiently. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) and cisplatin (Pt) have shown synergistic effects on a variety of cancers during preclinical and clinical studies. However, the ratio of the two drugs often could not be precisely regulated in different delivery systems, which hinders the desired synergistic effect. In addition, the low delivery efficiency of the two drugs to the tumor further impedes the ideal therapeutic outcomes. Herein, we report that a platelet-mimicking supramolecular nanomedicine (SN) could precisely control of the ratio of CPT and Pt with a high tumor accumulation rate for cascade amplification of synergistic chemotherapy. The SN was fabricated via the host–guest interaction between cucurbit[7]uril conjugated hyaluronic acid (HA-CB[7]) and adamantane (ADA) respectively functionalized CPT- and Pt-based prodrugs. The ratio of CPT and Pt in the SN could be facilely regulated by simply controlling the loading ratio, based on the strong binding affinity between CB[7] and ADA, and SN60 with 60% CPT and 40% Pt showed the highest synergistic effects on 4T1 cells. To improve the tumor accumulation efficiency of SN, 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a tumor vasculature-disruptive agent) was loaded into the optimized SN and then coated with platelet membrane to yield platelet-mimicking supramolecular nanomedicine (D@SN-P). D@SN-P could first passively accumulate in tumors owing to the enhanced permeability and retention (EPR) effect after intravenous administration. The initially release of DMXAA from D@SN-P could induce tumor vascular disruption, and the resultant epithelial collagen exposure around the disrupted tumor vasculature provided a target for further recruitment of platelet-mimicking SN, leading to cascade amplification of tumor accumulation with synergistic chemotherapy. Hence, this platelet-mimicking supramolecular nanomedicine presents a universal supramolecular strategy to finely regulate the ratio of loaded pro-drugs, and improve the accumulation efficiency to amplify chemotherapy via platelet-mimics. This work developed a platelet-mimicking supramolecular nanomedicine (D@SN-P) with a precisely regulated prodrugs for cascade amplification of synergistic chemotherapy. The resultant D@SN-P possessed an optimized ratio of ADA conjugated CPT- and Pt-based prodrugs via facile host–guest complexation between CB[7] and ADA to maximize the synergistic chemotherapy. D@SN-P could passively accumulate in tumors owing to the enhanced permeability and retention effect after intravenous administration. And initially release of DMXAA from D@SN-P would induce tumor vascular disruption, followed by epithelial collagen exposure arround the disrupted tumor vasculature, which then would provide a target for the specific binding of the platelets (including platelet-mimicking SN), leading to cascade amplification of synergistic chemotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Diamondoids, of which adamantane (C 10 H 16 ) is the simplest representative, constitute an intriguing class of carbon based nanomaterials with interesting chemical, mechanical and opto-electronic properties. While neutral diamondoids have been extensively studied for decades, their cationic counterparts were a subject of recent experimental investigations motivated by their potential role in astrochemistry. Here, we perform a computational study of the adamantane cation (C 10 H 16 + ) complementing the recent experimental findings. Specifically, we extend earlier theoretical work on vibrationally resolved electronic spectroscopy by accounting for the higher lying electronically excited states of the cation in the absorption and photoelectron spectra. We also perform adiabatic and nonadiabatic (surface hopping) molecular dynamics simulations to study (fast) fragmentation processes and electronic relaxation of C 10 H 16 + . Our simulations reveal that after excitation with near-infrared–ultraviolet photons, the adamantane cation undergoes an ultrafast internal conversion to the ground (doublet) state (on a time scale of 10–100 fs depending on initial excitation energy) which can be followed by a fast fragmentation, predominantly H loss. The yield of the ultrafast hydrogen dissociation as a function of excitation energy is reported. [ABSTRACT FROM AUTHOR]

Nanoparticle (NP) supra‐assembly offers unique opportunities to tune macroscopic hydrogels' mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)‐responsive NPs are physically cross‐linked with hyaluronic acid (HA) through guest‐host chemistry to create shear‐thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)‐b‐poly(N,N‐dimethylacrylamide)‐b‐poly(N,N‐dimethylacrylamide‐co‐N‐(1‐adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self‐assembled into NPs displaying adamantane on their surface. Self‐assembled NPs are mixed with β‐cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA‐only hydrogels, susceptibility to oxidative/enzymatic degradation, and inherent cell‐protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self‐assembled NPs significantly impacts hydrogel mechanical properties and shear‐thinning behavior, while ROS‐reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA‐only hydrogels. This study provides insight into polymer structure‐function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear‐thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells. [ABSTRACT FROM AUTHOR]

A new synthesis of racemic 1,2-diaminoadamantane was accomplished, its resolution into enantiomers through diastereomeric salts with l-tartaric acid was carried out, which gave individual (S)-enantiomer in 26% yield. It was reacted with carbon disulfide to obtain (S)-octahydro-3a,7:5,9-dimethanocycloocta[d]imidazole-2(3H)-thione, for which an enantiomeric excess of 96% was determined by HPLC. The absolute (S)-configuration was inferred from the results of quantum mechanical calculations of optical rotation. A number of N-donor ligands were synthesized based on (S)-1,2-diaminoadamantane. The catalytic activity of their complexes with CuII, MnIII, and NiII was studied on the model Henry, Michael, and epoxidation reactions. [ABSTRACT FROM AUTHOR]

Adamantane, the smallest diamondoid molecule with a symmetrical cage, contains two distinct carbon sites, CH and CH 2 . The ionization/excitation of the molecule leads to the cage opening and strong structural reorganization. While theoretical predictions suggest that the carbon site CH primarily causes the cage opening, the role of the other CH 2 site remains unclear. In this study, we used advanced experimental Auger electron–ion coincidence techniques and theoretical calculations to investigate the fragmentation dynamics of adamantane after resonant inner-shell photoexcitation. Our results demonstrate that some fragmentation channels exhibit site-sensitivity of the initial core–hole location, indicating that different carbon site excitations could lead to unique cage opening mechanisms. [ABSTRACT FROM AUTHOR]

A series of N,N′-disubstituted ureas containing a pyridine or quinoline fragment and a lipophilic adamantane moiety (13 examples, 53–94% yield) have been synthesized by the reaction of N,N-dimethyl-N′-(pyridin-2-yl or quinoline-2-yl)ureas with amine hydrochlorides. The synthesized compounds differed from each other by the position of substitution in the adamantane fragment, structure of the alkyl linker between the adamantane fragment and amide group, and heterocyclic substituent. They are potential target-oriented inhibitors of human soluble epoxide hydrolase (sEH). [ABSTRACT FROM AUTHOR]

A promising strategy in the synthesis of functional compounds with a cage structure is the use of 1,3-dehydroadamantane (tetracyclo[3.3.1.1.3,7.0.1,3]decane; 1,3-DHA; bridging [3.3.1]propellane) and its derivatives that are capable of restoring the adamantane structure in their reactions. The review provides information on the methods for the synthesis of 1,3-DHA, spectral characteristics, probable intermediates generated from propellanes, and the advantages of their using: low-stage syntheses of difficult-to synthesize adamantane derivatives, atomic precision, and "green chemistry." The reactions of 1,3-DHA with a wide range of organic compounds are considered, and its reactivity with respect to CH-, NH-, OH-, and SH-acids, as well as arenes, hydantoins, and heterocyclic compounds, is compared. New chemo- and regioselective methods for the one-step introduction of a 1-adamantyl group into the molecules of various substrates are classified. Particular attention is paid to the reactions of 1,3-DHA with various C–H acids, which enable the easy formation of C–CAd bonds to give hard-to-synthesize adamantane derivatives. The influence of pKa of the substrate on the selectivity of the reactions is demonstrated. Low-step methods for the synthesis of new adamantane derivatives, which have shown high activity as hsEH epoxide hydrolase inhibitors and antitumor agents, are described. [ABSTRACT FROM AUTHOR]

The relaxation of the components of the multiple-quantum NMR spectrum of a solid under the effect of the dipole–dipole interactions during the evolution period is considered. It is taken into account that clusters of dynamically correlated spins of different sizes are formed in the preparatory period, and their degradation depends on their size and coherence order. To calculate the size distribution function of clusters and their degradation function, a physical model including relaxation processes is developed. Using this model, an analytical result for a multiple-quantum spectrum is obtained. Agreement is obtained between the theoretical and experimental dependences of the coherence degradation rates in adamantane scaled by the square root of the average cluster size. The parameters of the above functions are found from the comparison of these dependences. [ABSTRACT FROM AUTHOR]

Novel dihydropyrimidines incorporating an adamantane motif have been synthesized using a three-component Biginelli reaction of adamantane-containing β-keto amide N-1-adamantyl acetoacetamide as active methylene compound, thiourea, and aromatic aldehydes in more convenient condition and high yields. The structures of the synthesized compounds were confirmed by spectral data. [ABSTRACT FROM AUTHOR]

3-(Adamantan-1-yl)-4-(4-fluorophenyl)-1-{[4-(2-methyoxyphenyl)piprazin-1yl]-methyl}-4,5-dihydro-1H-1,2,4-triazole-5-thione (AFT) was synthesized and spectroscopic investigations have been made experimentally and theoretically. The electrostatic potential maps and frontier orbital visualizations were used to comment of molecular polarity and stability in AFT. In AFT, thione group, methoxyphenyl ring, and triazole are the strongest repulsion and attractive reactive sites. The chemical descriptors in different solvents and NLO properties are predicted. For different solvents and gas phase, UV-vis theoretical spectra are being used to assess the electronic transition. Solvation free energy in water (hydration free energy) indicates good solubility of AFT in an aqueous medium, factor that corroborates the biological activity, in as much as that bioorganic processes occur in aqueous medium. Solvation produces a lowering of absorption in the UV-vis region. After evaluating the drug likeness properties, the title compound was examined for its analgesic activity by means of molecular docking and MD simulations. The MD simulations and docking studies suggested inhibitory activity against analgesic protein glutamate receptor. [ABSTRACT FROM AUTHOR]

The title compound, 1-(3-isoselenocyanatopropyl)adamantane, was synthesized for the first time from 3-(adamantan-1-yl)propan-1-amine by the two-stage reaction with 1-(3-isocyanopropyl)adamantane as intermediate. The product was characterized by NMR, GC-MS, and elemental analysis. [ABSTRACT FROM AUTHOR]

Metallothioneins (MTs) constitute an important family of metal binding proteins. Mollusk MTs, in particular, have been used as model systems to better understand the evolution of their metal binding features and functional adaptation. In the present study two recombinantly produced MTs, LgiMT1 and LgiMT2, and their de novo evolved γ domain, of the marine limpet Lottia gigantea, were analyzed by electronic spectroscopy and mass spectrometry. Both MT proteins, as well as their γ domains, exhibit a strong binding specificity for Cd(II), but not for Zn(II) or Cu(I). The LgiMTs' γ domain renders an MII4(SCys)10 cluster with an increased Cd stoichiometry (binding 4 instead of 3 Cd2+ ions), representing a novel structural element in the world of MTs, probably featuring an adamantane 3D structure. This cluster significantly improves the Cd(II)-binding performance of the full length proteins and thus contributes to the particularly high Cd coping capacity observed in free-living limpets. [ABSTRACT FROM AUTHOR]

The electrochemical ion‐sensor performance of the self‐assembled monolayer (SAM) of 3H‐imidazo[4,5‐b]pyridine, which is known as a metal ionophore, was examined using a triad composed of ferrocene, an ionophore, and a tripodal trithiol with adamantane core. The voltammetry of the SAM‐modified Au electrode showed a large positive change (280 mV) in the ferrocene oxidation potential via the addition of Pb2+, with a detection limit of 10–6 M. A Langmuir adsorption‐type analysis of the ion binding equilibrium suggested that as much as 70% of the imidazopyridine ligand was actually functioning as a Pb2+ ionophore on the SAM, whereas the rest of the ligand was uncomplexed because of the crowding of the molecules in the SAM. Control experiments using an analogous triad of monothiol revealed a strong advantage in using trithiol; thus, tripod‐shaped anchor is requisite for the ionophore to function well as a sensor. [ABSTRACT FROM AUTHOR]

It was shown that the optical and dielectric properties of polyimides (PIs) are affected by both the presence of an alicyclic fragment and the non-coplanarity of the structural elements of the polymer chain. The combination of these factors contributed to an increase of the transparency of the PIs in the optical range and a decrease of the dielectric constant. It was determined that the introduction of 20 mol.% adamantane-containing diamine into the PI structure contributed to its more complete amorphization and increased its transparency. [ABSTRACT FROM AUTHOR]

Rapid development of the copper-catalyzed amination of aryl halides in the beginning of the 21st century, known as the Renaissance of the Ullmann chemistry, laid foundations for the use of this method as a powerful tool for the construction of the C(sp2)-N bond and became a rival of the Buchwald–Hartwig amination reaction. Various applications of this approach are well-documented in a number of comprehensive and more specialized reviews, and this overview in the form of a personal account of the Cu-catalyzed arylation and heteroarylation of the adamantane-containing amines, and di- and polyamines, covers a more specific area, showing the possibilities of the method and outlining general regularities, considering reagents structure, copper source and ligands, scope, and limitations. The material of the last decade is mainly considered, and recent data on the application of the unsupported copper nanoparticles and possibilities of the Chan-Lam reaction as an alternative to the use of aryl halides are also discussed. [ABSTRACT FROM AUTHOR]