Piotr Piątek

Selective Ammonium Nitrate Recognition by a Heteroditopic Macrotricyclic Ion-Pair Receptor

The heteroditopic macrotricyclic molecular receptor 1, which bears a tripodal anion binding domain and 4,10,16-triaza-18-crown-6 cation recognition domain, proves to be an effective ion-pair receptor. In the absence of the cobound cation (TBA(+) salts) receptor 1 preferably binds nitrate and nitrite over other anions, including basic anions such as acetate or dihydrogenphosphate. Ammonium cation binding by the 4,10,16-triaza-18-crown-6 subunit significantly enhances the strength of the nitrate and nitrite complexation at the triamide recognition site of the receptor. In the presence of ammonium cations, the association constants of nitrate binding reach an impressive value of 1050 M(-1) in highly polar DMSO-d6. Interestingly, the binding of other anions such as chloride and bromide is not enhanced in the presence of a cobound NH4(+) cation. The increased affinity of [1·NH4(+)]PF6(-) for anionic species is attributed to a strong cooperative effect that arises from the properly positioned binding sites in the receptor 1 cavity, thus allowing for the formation of the ion pair. Under liquid/liquid conditions, receptor 1 is able to extract NH4NO3 from an aqueous to an organic phase, as inferred from (1)H NMR spectroscopic and nitrite/nitrate colorimetric analyses.

Tuning the binding properties of a new heteroditopic salt receptor through embedding in a polymeric system

In this communication, we describe a polymerizable, heteroditopic salt receptor, based on an amino acid scaffold, which is able to bind sodium salts of chloride, acetate and nitrate. A poly(butyl methacrylate) derivative containing receptor was then prepared. In contrast to receptor copolymer is capable of extracting sodium nitrate from aqueous media.

Selective NaNO2 recognition by a simple heteroditopic salt receptor based on L-ornithine molecular scaffold

This paper describes the development of a simple heteroditopic salt receptor consisting of aza-18-crown-6 (a cation binding domain), nitrophenylurea (an anion binding domain) and an additional metacrylamide group appended to the carboxylic, α-amine and δ-amino groups of L-ornithine. Detailed binding studies showed that this receptor is capable of effectively and selectively binding NaNO2 salt.

The use of the Mitsunobu reaction in preparation of chiral synthons for macrocyclic frameworks

Abstract The Mitsunobu reaction was used for the synthesis of chiral diesters 2 and 6 and chiral diamine 4 . Five new chiral macrocyclic bisamides were synthesized, starting from these precursors.

Cooperative ion pair recognition by multitopic L-ornithine based salt receptors

The L-ornithine scaffold was used to develop molecular receptors with improved efficacy in ion pair binding. With two appropriately oriented strong anion binding domains (urea and (thio)urea groups) and one cation binding group (crown ether moiety), these receptors exhibit effective association with the sodium salts of selected anions. We show that the simultaneous action of the two anion binding domains, reinforced by cation coordination, is responsible for the binding strength of receptors 1 and 2. The binding constants for the anions and sodium salt complexes of these receptors were determined using spectrophotometric and 1H NMR titration measurements. Besides carboxylate ions, in the presence of sodium cations all the selected anions associate with receptors 1 and 2 in a positive cooperative manner. The strongest cooperative binding was observed for the association of sodium chloride with receptor 2, supported by urea and thiourea anion binding domains (Ka = 85 500 M−1). Lacking two strong anion binding domains, receptors 4 and 5 can only interact with sodium chloride much more weakly (Ka = 5100 and 8900 M−1, respectively).

1H, 13C, 15N NMR and X-Ray Diffractometry in Structural Studies of Macrocyclic Lactams Containing Pyridine Moiety

Abstract We examined complexing sites of the Pb2+ complex of the macrocyclic lactam 1 using 15N NMR and other spectroscopies and we have found that the amide groups undergo conformational changes to allow the complexation process to proceed via the pyridine nitrogen atom and carbonyl and ethereal oxygen atoms. X-Ray analysis of compound 1 was carried out successfully. Space group I41/a, a=28.332(4)Å, b=28.332(4)Å, c=10.7379(4)Å, Z=16, V=8619.3(18)Å3, Dc=1.197gcm−3, R1=0.0479 (based on 2510 reflections I>2[sgrave](I). It shows presence of intramolecular hydrogen bonds, which are broken during the complexation. Molecules form supramolecular tetragonal assemblies in the crystal, which form channels the walls of which are 7.42 Å apart.

An ion pair receptor facilitating the extraction of chloride salt from the aqueous to the organic phase

A new multitopic salt receptor based on an L-ornithine scaffold was synthesized using a simple approach; this receptor consists of a crown ether based cation and two squaramide anion binding domains. The binding properties of this receptor were measured spectrophotometrically, in acetonitrile solution. A comparative binding study of reference receptors enabled the evaluation of the role of particular binding domains in salt binding. The collected data revealed a stronger contribution of the anion binding domain located in the side chain of amino acid than the α-supported one. The cooperative action of these two binding domains is needed to strongly associate salts. Receptor 1 was found to be able to extract chloride salt from the aqueous to the organic phase.

Chiral α,ω-diaminoethers derived from d-mannitol and l-treitol as building blocks for the synthesis of macrocyclic compounds possessing 1,3-benzenedicarboxamide or 2,6-pyridinedicarboxamide subunits

Abstract Three new chiral α,ω-diaminoethers, derivatives of d -mannitol and l -treitol, possessing C 2 symmetry are prepared. The α,ω-diaminoethers were applied to the macrocyclization reaction under non-high-dilution conditions, which afforded chiral macrocyclic diamides possessing either 2,6-pyridinedicarboxamide or 1,3-benzenedicarboxamide moieties.

Highly effective ion-pair receptors based on 2,2-bis(aminomethyl)-propionic acid

Compounds 2 and 3 were designed and prepared as heteroditopic ion-pair receptors. The design features a 2,2-bis(aminomethyl)propionic acid core to connect and pre-organize binding groups. The cation binding is provided by a sodium selective N-acyl aza-18-crown-6 subunit whereas for anion complexation, two urea groups (receptor 2) or two squaramide groups (receptor 3) were introduced. Beyond acting as anion binding sites, the urea and squaramide groups were used to support sodium cation complexation through metal carbonyl oxygen lone pair interactions. The receptors were found to bind sodium salts of chloride, bromide and nitrate much more strongly than the corresponding ions accompanied by counterions that do not coordinate to the receptor. For example, chloride binding to receptor 2 enhances the strength of sodium complexation by up to 23 times. Conversely, sodium binding enhances chloride recognition by a factor of three. Receptor 3 containing squaramide units, binds sodium chloride and bromide with a similar albeit lower cooperativity. Moreover, unprecedentedly tight binding of these salts was achieved, with association constants as high as log Ka = 6.52 M-1 for NaCl salt complexation.

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.