Guest-Mediated Reversal of the Tumbling Process in Phosphorus-Dendritic Compounds Containing β-Cyclodextrin Units: An NMR Study

The conformational study of dendritic platforms containing multiple β-cyclodextrin (βCD) units in the periphery is relevant to determine the availability of βCD cavities for the formation of inclusion complexes in aqueous biological systems. In this work, we performed a detailed conformational analysis in D2O, via 1D and 2D NMR spectroscopy of a novel class of phosphorus dendritic compounds of the type P3N3-[O-C6H4-O-(CH2)n-βCD]6 (where n = 3 or 4). We unambiguously demonstrated that a functionalized glucopyranose unit of at least one βCD unit undergoes a 360° tumbling process, resulting in a deep inclusion of the spacer that binds the cyclodextrin to the phosphorus core inside the cavity, consequently limiting the availability of the inner cavities. In addition, we confirmed through NMR titrations that this tumbling phenomenon can be reversed for all βCD host units using a high-affinity guest, namely 1-adamantanecarboxylic acid (AdCOOH). Our findings have demonstrated that it is possible to create a wide variety of multi-functional dendritic platforms.

Structural Insights into the Host–Guest Complexation between β-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives

Understanding the host–guest chemistry of α-/β-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used β-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH2), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCH2COOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, β-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives. These inclusion complexes can be terminated as (adm-1-OH)2⊂CD2 (1, 2:2), (adm-2-OH)3⊂CD2 (2, 3:2), (adm-1-NH2)3⊂CD2 (3, 3:2), (adm-1-COOH)2⊂CD2 (4, 2:2), (adm-1,3-diCOOH)⊂CD2 (5, 1:2), and (adm-1,3-diCH2COOH)⊂CD2 (6, 1:2). This work may shed light on the design of nanomedicine with hierarchical structures, mediated by delicate cyclodextrin-based hosts and adamantane-appended drugs as the guests.

Determination of the anticancer properties of cis- and trans-diadamanthylcarboxylates of dirhenium(III)

The aim of the study. The aim of the work was to investigate in vivo anticancer activity of cis- and trans-diadamanthylcarboxylates of dirhenium(III) alone and together with cisplatin in form of nanobins.Materials and methods. Model of tumor growth, Guerin’s carcinoma; intraperitoneal administration of cisplatin, dirhenium(III) compounds in liposomes and of binary liposomes, containing both cytostatics; volumes and final weights of tumors were measured.Results. In vivo antitumor properties of two dirhenium(III) dicarboxylates with 1-adamantanecarboxylic acid moieties as ligands with cis- (I) and trans- (II) orientation of the carboxylic groups around a cluster fragment alone and together with cisplatin were presented; an attempt to understand differences in a possible mechanism of anticancer activity of the substances were undertaken. Antiradical and DNA-binding properties of I and II were the matter of consideration.Conclusions. Cis- and trans- compounds of dirhenium I and II had close antitumor activity in vivo with a little bit superiority of the cis- analog. Mechanisms of anticancer activity of I and II are different and may also include monofunctional adduct formation and subsequent interstrand cross-linking for the II substance, formation of protein-DNA cross-links, etc.

Synthesis of Novel N-(R)-2-(1-Adamantyl)-1H-Benzimidazole-5(6)-Carboxamide, Carbohydrazide and 1,3,4-Oxadiazole Derivatives

: A novel series of benzimidazole-5(6)-carboxamide 3a-g, carbohydrazide 5a-e and 1,3,4-oxadiazole 6a-g derivatives bearing adamantane moiety were synthesized. The synthesis of benzimidazole heterocycle was performed by direct condensation/cyclization reaction of 1-adamantanecarboxylic acid with methyl 3,4-diaminobenzoate in Trimethylsilyl Polyphosphate (PPSE). The obtained Methyl 2-(1-adamantyl)-1H-benzimidazole-5(6)-carboxylate was converted to desired carboxamide and carbohydrazide derivatives in two different ways. In the first case, the synthesized ester after hydrolysis was converted to acid chloride and subsequently coupled with different aromatic and heterocycle amines to give carboxamide derivatives. In the second case, treatment with hydrazine hydrate gave corresponding 2-(1-adamantyl)-1Hbenzimidazole-5(6)-carbohydrazide which was coupled with some acyl chlorides to give appropriate carbohydrazide derivatives and with some aromatic acids to give 1,3,4-oxadiazole derivatives.

Shape controlled assembly of carboxylic acids: formation of a binary monolayer by intercalation into molecular nanotunnels

Peekaboo on the nanoscale: exposure to molecules of adamantanecarboxylic acid leaves a layer of benzenetricarboxylic acid seemingly unchanged.

An Efficient and Practical Method for the Synthesis of Saxagliptin Intermediate 2-(3-Hydroxy-1-adamantane)-2-oxoacetic Acid and Its Optimization

A mild and relatively simple way for preparation of 2-(3-hydroxy-1-adamantane)-2-oxoacetic acid (I) was reported. It was prepared from 1-adamantanecarboxylic acid (II) via sulfuric acid/nitric acid to get 3-hydroxy-1-adamantanecarboxylic acid (III); treated with the one-pot method through acylation, condensation, and decarboxylation to obtain 3-hydroxy-1-acetyladamantane (IV); and finally oxidized by potassium permanganate (KMnO4) to get the target compound (I). The overall yield was about 60%, which provides a new idea for commercial production of saxagliptin intermediate.

Facile Synthesis of 3-(Azol-1-yl)-1-adamantanecarboxylic Acids—New Bifunctional Angle-Shaped Building Blocks for Coordination Polymers

For the first time, orthogonally substituted azole-carboxylate adamantane ligands were synthesized and used for preparation of coordination polymers. The angle-shaped ligands were prepared by the reaction of 1-adamantanecarboxylic acid and azoles (1H-1,2,4-triazole, 3-methyl-1H-1,2,4-triazole, 3,5-dimethyl-1H-1,2,4-triazole, 1H-tetrazole, 5-methyl-1H-tetrazole) in concentrated sulfuric acid. Variation of the solvent and substituents in azole rings allowed to prepare both 1D and 2D copper(II) and nickel(II) coordination polymers, [Cu2(trzadc)4(H2O)0.7]∙DMF∙0.3H2O, [Cu(trzadc)2(MeOH)]∙MeOH, [Ni(trzadc)2(MeOH)2] and [Cu2(mtrzadc)3(MeOH)]+NO3– (trzadc-3-(1,2,4-triazol-1-yl)-adamantane-1-carboxylic acid; mtrzadc-3-(3-methyl-1,2,4-triazol-1-yl)-adamantane-1-carboxylic acid) which were structurally characterized by single crystal X-ray diffraction. Complex [Cu(trzadc)2(MeOH)]∙MeOH was shown to act as a catalyst in the Chan-Evans-Lam arylation reaction.