Chemical Probes for Blocking of Influenza A M2 Wild-type and S31N Channels.

We report on using the synthetic aminoadamantane-CH2-aryl derivatives 1-6 as sensitive probes for blocking M2 S31N and influenza A virus (IAV) M2 wild-type (WT) channels as well as virus replication in cell culture. The binding kinetics measured using electrophysiology (EP) for M2 S31N channel are very dependent on the length between the adamantane moiety and the first ring of the aryl headgroup realized in 2 and 3 and the girth and length of the adamantane adduct realized in 4 and 5. Study of 1-6 shows that, according to molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, all bind in the M2 S31N channel with the adamantyl group positioned between V27 and G34 and the aryl group projecting out of the channel with the phenyl (or isoxazole in 6) embedded in the V27 cluster. In this outward binding configuration, an elongation of the ligand by only one methylene in rimantadine 2 or using diamantane or triamantane instead of adamantane in 4 and 5, respectively, causes incomplete entry and facilitates exit, abolishing effective block compared to the amantadine derivatives 1 and 6. In the active M2 S31N blockers 1 and 6, the phenyl and isoxazolyl head groups achieve a deeper binding position and high kon/low koff and high kon/high koff rate constants, compared to inactive 2-5, which have much lower kon and higher koff. Compounds 1-5 block the M2 WT channel by binding in the longer area from V27-H37, in the inward orientation, with high kon and low koff rate constants. Infection of cell cultures by influenza virus containing M2 WT or M2 S31N is inhibited by 1-5 or 1-4 and 6, respectively. While 1 and 6 block infection through the M2 block mechanism in the S31N variant, 2-4 may block M2 S31N virus replication in cell culture through the lysosomotropic effect, just as chloroquine is thought to inhibit SARS-CoV-2 infection.

Diamantane Suspended Single Copper Atoms.

Single chains of metal atoms are expected to be perfect one-dimensional nanowires in nanotechnology, due to their quantum nature including tunable electronic or spin coupling strengths. However, it is still rather difficult to fabricate such nanowires with metallic atoms under directional and separation control. Here, we succeeded in building higher-order single diamondoid-chains from the lower-order chains using a chemically well-controlled approach that employs diamondoids on metal surfaces. This approach results in higher-order diamondoid double chains by linking two neighboring single chains, and ultimately forms a central chain consisting of single Cu atoms suspended by the diamantane framework. The suspended Cu atoms are placed above the metal surface with a periodic distance of 0.67 ± 0.01 nm. Our bottom-up approach will allow detailed experimental investigations of the properties of these exciting suspended metal atoms (for example, quantized conductance, spin coupling, as well as transfer, etc.). Furthermore, we also identified different spatial configurations on the metal surfaces in on-surface reaction processes using high-resolution AFM imaging and density functional theory computations. Our findings broaden the on-surface synthesis concept from 2D planar aromatic molecules to 3D bulky aliphatic molecules.

One-dimensional hydrogen bonding networks of bis-hydroxylated diamantane formed inside double-walled carbon nanotubes.

1,6-Bis(hydroxymethyl)diamantane spontaneously aligns inside double-walled carbon nanotubes. The encapsulated molecules form a one-dimensional network within the double-walled carbon nanotubes through hydrogen bonding that leads to a highly dense filling as compared to unfunctionalized diamantane. Improving the encapsulation yields of precursors via functionalization is crucial to prepare novel one-dimensional materials.

Host-Guest Complexes of Cyclodextrins and Nanodiamonds as a Strong Non-Covalent Binding Motif for Self-Assembled Nanomaterials.

We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by ß-cyclodextrin and γ-cyclodextrin (ß-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host-guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with ß-CD. We found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantane as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host-guest association: adamantane showed lower agglutination than di- or triamantane with ß-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV.

Template Synthesis of Linear-Chain Nanodiamonds Inside Carbon Nanotubes from Bridgehead-Halogenated Diamantane Precursors.

A simple method for the synthesis of linear-chain diamond-like nanomaterials, so-called diamantane polymers, is described. This synthetic approach is primarily based on a template reaction of dihalogen-substituted diamantane precursors in the hollow cavities of carbon nanotubes. Under high vacuum and in the presence of Fe nanocatalyst particles, the dehalogenated radical intermediates spontaneously form linear polymer chains within the carbon nanotubes. Transmission electron microscopy reveals the formation of well-aligned linear polymers. We expect that the present template-based approach will enable the synthesis of a diverse range of linear-chain polymers by choosing various precursor molecules. The present technique may offer a new strategy for the design and synthesis of one-dimensional nanomaterials.

Selective preparation of diamondoid phosphonates.

We present an effective sequence for the preparation of phosphonic acid derivatives of the diamondoids diamantane, triamantane, [121]tetramantane, and [1(2,3)4]pentamantane. The reactions of the corresponding diamondoid hydroxy derivatives with PCl3 in sulfuric or trifluoroacetic acid give mono- as well as didichlorophosphorylated diamondoids in high preparative yields.

Electronic structure tuning of diamondoids through functionalization.

We investigated the changes in electronic structures induced by chemical functionalization of the five smallest diamondoids using valence photoelectron spectroscopy. Through the variation of three parameters, namely functional group (thiol, hydroxy, and amino), host cluster size (adamantane, diamantane, triamantane, [121]tetramantane, and [1(2,3)4]pentamantane), and functionalization site (apical and medial) we are able to determine to what degree these affect the electronic structures of the overall systems. We show that unlike, for example, in the case of halobenzenes, the ionization potential does not show a linear dependence on the electronegativity of the functional group. Instead, a linear correlation exists between the HOMO-1 ionization potential and the functional group electronegativity. This is due to localization of the HOMO on the functional group and the HOMO-1 on the diamondoid cage. Density functional theory supports our interpretations.

Reactivities of the prism-shaped diamondoids [1(2)3]tetramantane and [12312]hexamantane (cyclohexamantane).

Various functional groups have been incorporated into the structures of the naturally occurring diamondoids [1(2)3]tetramantane and [12312]hexamantane (cyclohexamantane), which represent hydrogen-terminated prism-shaped nanodiamonds. The selectivities of the C-H substitutions in [1(2)3]tetramantane depend on the reagent employed and give products substituted at either central (through bromination) or peripheral (through nitroxylation and photo-oxidation) positions. The hydrogen-coupled electron-transfer mechanism of C-H nitroxylation with the model electrophile NO(2)(+)...HNO(3) was verified computationally at the B3PW91 and MP2 levels of theory by utilizing the 6-31G(d) and cc-pVDZ basis sets. The thermodynamically controlled nitroxylation/isomerization of [1(2)3]tetramantane allows the preparation of peripherally trisubstituted derivatives, which were transformed into tripod-like nanodiamond building blocks. The bromination of cyclohexamantane selectively gives the 2-bromo derivative, reproducing the chemical behavior of the {111} surface of the hydrogen-terminated diamond.

Simple preparation of diamondoid 1,3-dienes via oxetane ring opening.

The transformations of apical mono- and bisacetyl diamondoids to the respective oxetanes and subsequent acid-catalyzed ring opening/dehydration lead to diamondoidyl mono- and bis-1,3-dienes in high preparative yields.

Reactivity of [1(2,3)4]pentamantane (Td-pentamantane): a nanoscale model of diamond.

To model the chemical properties of the hydrogen-terminated nanodiamond {111} and {110} surfaces, the functionalizations of the higher diamondoid [1(2,3)4]pentamantane were studied. [1(2,3)4]Pentamantane reacts selectively with neat bromine to give the medial 2-mono- and 2,4-disubstitution products. In contrast, oxidation with nitric acid as well as single-electron-transfer oxidation involving the [1(2,3)4]pentamantane radical cation results in apical C7-substitutions. This substitution pattern dominates in the free-radical bromination under phase-transfer catalytic conditions that gives a mixture of 7- and 2-bromo[1(2,3)4]pentamantane in a 95:5 ratio. Replacement of the functional groups in [1(2,3)4]pentamantane occurs without isomerization. This was demonstrated for the interconversions of the bromo and hydroxy derivatives as well as for the preparation of [1(2,3)4]pentamantyl-7-thiol from 7-hydroxy[1(2,3)4]pentamantane. Thus, the selective functionalization of hydrogen-terminated nanodiamonds is possible by means of reactions with common electrophiles-oxidizers.

Functionalized nanodiamonds: triamantane and [121]tetramantane.

The selective functionalizations of the fundamental hydrogen-terminated nanodiamonds triamantane 1, as well as the most symmetrical representative of the tetramantanes (C(2h)-[121]tetramantane 2) were elaborated. Electrophilic reagents (Br2, HNO3) predominantly attack the medial C-H positions of the cages; bromination of 2 gave the medial 2-bromo derivative almost exclusively. Highly selective apical substitution in 1 and 2 is possible either under single-electron-transfer oxidations via hydrocarbon radical cations or through photoacetylation with diacetyl. The mono- and the bis-acetyl derivatives of 1 and 2 were converted through Bayer-Villiger oxidation and subsequent hydrolysis to the respective apical mono- and dihydroxy derivatives. This exceptional synthetic specificity facilitates the transformation of 2, and perhaps larger nanodiamond molecules, into functionalized building blocks needed for a wide range of applications such as nanotechnology.

Functionalized nanodiamonds part 3: thiolation of tertiary/bridgehead alcohols.

[reaction: see text] Treatment of acyclic as well as polycyclic tertiary mono- and dihydroxy hydrocarbon derivatives with thiourea in the presence of hydrobromic and acetic acid represents a convenient one-step route to the respective tertiary thiols and dithiols. This procedure was used for the preparation of diamondoid thiols of diamantane, triamantane, [121]tetramantane, and others that are prospective nanoelectronic materials.