Jakub Wojciechowski

Synthesis, Characterization, and Antimicrobial Activity of Silver(I) and Copper(II) Complexes of Phosphate Derivatives of Pyridine And Benzimidazole

Two silver(I) complexes—{[Ag(4‐pmOpe)]NO3}n and [Ag(2‐bimOpe)2]NO3—and three copper(II) complexes—[Cu4Cl6O(2‐bimOpe)4], [CuCl2(4‐pmOpe)2], and [CuCl2(2‐bis(pm)Ope]—were synthesized by reaction of silver(I) nitrate or copper(II) chloride with phosphate derivatives of pyridine and benzimidazole, namely diethyl (pyridin‐4‐ylmethyl)phosphate (4‐pmOpe), 1H‐benzimidazol‐2‐ylmethyl diethyl phosphate (2‐bimOpe), and ethyl bis(pyridin‐2‐ylmethyl)phosphate (2‐bis(pm)Ope). These compounds were characterized by 1H, 13C, and 31P NMR as well as IR spectroscopy, elemental analysis, and ESIMS spectrometry. Additionally, molecular and crystal structures of {[Ag(4‐pmOpe)]NO3}n and [Cu4Cl6O(2‐bimOpe)4] were determined by single‐crystal X‐ray diffraction analysis. The antimicrobial profiles of synthesized complexes and free ligands against test organisms from the ATCC and clinical sources were determined. Silver(I) complexes showed good antimicrobial activities against Candida albicans strains (MIC values of ∼19 μM). [Ag(2‐bimOpe)2]NO3 was particularly active against Pseudomonas aeruginosa and methicillin‐resistant Staphylococcus epidermidis, with MIC values of ∼5 and ∼10 μM, respectively. Neither copper(II) complexes nor the free ligands inhibited the growth of test organisms at concentrations below 500 μg mL−1.

A hydantoin isoform of cyclic N6-threonylcarbamoyladenosine (ct6A) is present in tRNAs

Abstract N6-Threonylcarbamoyladenosine (t6A) and its derivatives are universally conserved modified nucleosides found at position 37, 3΄ adjacent to the anticodon in tRNAs responsible for ANN codons. These modifications have pleiotropic functions of tRNAs in decoding and protein synthesis. In certain species of bacteria, fungi, plants and protists, t6A is further modified to the cyclic t6A (ct6A) via dehydration catalyzed by TcdA. This additional modification is involved in efficient decoding of tRNALys. Previous work indicated that the chemical structure of ct6A is a cyclic active ester with an oxazolone ring. In this study, we solved the crystal structure of chemically synthesized ct6A nucleoside. Unexpectedly, we found that the ct6A adopted a hydantoin isoform rather than an oxazolone isoform, and further showed that the hydantoin isoform of ct6A was actually present in Escherichia coli tRNAs. In addition, we observed that hydantoin ct6A is susceptible to epimerization under mild alkaline conditions, warning us to avoid conventional deacylation of tRNAs. A hallmark structural feature of this isoform is the twisted arrangement of the hydantoin and adenine rings. Functional roles of ct6A37 in tRNAs should be reconsidered.

On the coordination behavior of the hmta toward zinc and cadmium cations in presence of sulfate(VI) and nitrate(V) anions

Zinc and cadmium sulfate and nitrate complexes with hexamethylenetetramine, [Zn(hmta)2(H2O)4]2+·[Zn(H2O)6]2+··6H2O (1), ·n·2nH2O (2), [Zn(H2O)6]2+·2(hmta)··4H2O (3) and [Cd(hmta)(NO3)2(H2O)2]n (4), have been synthesized and characterized by elemental and thermal analysis, IR spectroscopy, and X-ray crystallography. Graphical Abstract

Three-component reaction of 3-(diethoxyphosphoryl)coumarin, enolizable ketones and primary amines: Simple, stereoselective synthesis of benzo[1,3]oxazocine skeletons

The synthesis of benzoxazocine phosphonates was accomplished by means of the three-component reaction of 3-(diethoxyphosphoryl)coumarin, enolizable ketones and benzylamine. An asymmetric version of this reaction was also developed. Treatment of the coumarin with cyclopentanone and (R)- or (S)-1-phenylethylamine afforded enantiomerically pure benzoxazocine phosphonates in a 2.5:1 diastereoisomeric ratio. In contrast, similar reaction with cyclohexanone provided α-phosphono-δ-enamides as single diastereoisomers. The mechanistic features of the reaction were discussed. A transition state model rationalizing its stereochemical outcome was proposed. The α-phosphono-δ-lactams obtained were transformed into the corresponding α-methylene-δ-lactams. The cytotoxicity of these compounds was evaluated.

X-ray investigations of bicyclic α-methylene-δ-valerolactones. V. (4aS,7R,8aR)-7-Isopropenyl-4a-methyl-3-methyleneperhydrochromen-2-one

The title compound, C(14)H(20)O(2), adopts a conformation in which the delta-valerolactone and cyclohexane rings are almost coplanar with one another. The gamma-methyl substituent occupies an axial position with respect to the cyclohexane ring. The delta-valerolactone moiety adopts an envelope arrangement, while the cyclohexane ring exists in a chair conformation.

On the Coordination Behaviour of the hmta Toward Alkali Metal Cations in Presence of Perchlorate Anions

The lithium and sodium perchlorate coordination compounds with hexamethylenetetramine of general formulas: [Li(H2O)4]+•2hmta•ClO4− (1) and [Na(ClO4)(H2O)(hmta)]n (2) have been synthesized, characterised by elemental and thermal analysis, IR spectroscopy and X-ray crystallography. The compound 2 is a rare three dimensional hybrid compound. The obtained compounds are air stable at room temperature and well soluble in water. As a result of the different electronic properties of the ions, the compounds differ considerably in the molecular structure and consequently in the properties. The studied compounds exhibit opposite placement of both hmta molecules and perchlorate ions: in an outer and inner coordination sphere, respectively, for 1 and 2. The thermal and spectroscopic properties were correlated with the studied compounds molecular structure.Graphical AbstractThe two novel coordination compounds {namely [Li(H2O)4]+•2hmta•ClO4− and [Na(ClO4)(H2O)(hmta)]n}, of which one is a rare three dimensional hybrid compound, have been synthesized and characterised by: elemental and thermal analysis, IR spectroscopy and X-ray crystallography.

X-ray investigations of bicyclic alpha-methylene-delta-valerolactones. III. trans-(4aR,8aR)-4a-Methoxy-3-methyleneperhydrochromen-2-one.

The title compound, C11H16O3, adopts a conformation in which the delta-valerolactone and cyclohexane rings are almost coplanar with one another. The beta-methoxy substituent occupies an axial position with respect to the cyclohexane ring. The delta-valerolactone moiety adopts a half-chair arrangement, while the cyclohexane ring exists in a chair conformation.

Synthesis of 3-Methylidene-1-tosyl-2,3-dihydroquinolin-4(1H)-ones as Potent Cytotoxic Agents

An efficient synthetic strategy to 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2‐(tosylamino)benzoate, condensation of thus formed diethyl 2‐oxo‐2‐(2‐N‐tosylphenyl)ethylphosphonate with various aldehydes followed by successful application of the obtained 3‐(diethoxyphosphoryl)‐1,2‐dihydroquinolin‐4‐ols as Horner–Wadsworth–Emmons reagents for the olefination of formaldehyde. Also, enantioselective approach to the target compounds has been evaluated using 3‐dimenthoxyphosphoryl group as a chiral auxiliary. Single X‐ray crystal analysis of (2S)‐3‐(dimenthoxyphosphoryl)‐2‐phenyl‐1‐tosyldihydroquinolin‐4‐ol revealed the presence of strong resonance‐assisted hydrogen bond (RAHB). The obtained 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones were then tested for their cytotoxic activity against two leukemia cell lines NALM‐6 and HL‐60 and a breast cancer MCF‐7 cell line. All compounds showed very high cytotoxic activity with the IC50 values mostly below 1 μm in all three cancer cell lines. The selected analogs were also tested on human umbilical vein endothelial cells (HUVEC) and on human mammary gland/breast cells (MCF‐10A) to evaluate their influence on normal cells. Since one of the most serious problems in cancer chemotherapy is the development of drug resistance, the mRNA levels and activity of ABCB1 transporter considered to be the most important factor engaged in drug resistance, were evaluated in MCF‐7 cells treated with two selected analogs. Both compounds were strong ABCB1 transporter inhibitors that could prevent efflux of anticancer drugs from cancer cells.

(2S,4R)-4-Ammonio-5-oxopyrrolidine-2-carboxylate

In the crystal structure of the title compound, C5H8N2O3, the molecules exist in the zwitterionic form. The pyrrolidine ring adopts an envelope conformation with the unsubstituted endocyclic C atom situated at the flap. The other four endocyclic atoms are coplanar with the exocyclic carbonyl O atom, with an r.m.s. deviation from the mean plane of 0.06 Å. The carboxylate substituent is located axially, while the ammonium group occupies an equatorial position. In the crystal structure, the molecules are linked through N—H⋯O hydrogen bonds, forming a three-dimensional network.

rac-(1S,2R)-Diethyl 6-hydr­oxy-1-(4-methoxy­phen­yl)-3-oxo-2,3-di­hydro-1H-benzo[f]chromen-2-yl]­phospho­nate

In the title compound, C24H25O7P, the δ-valerolactonyl ring exists in a distorted screw-boat conformation with the diethoxyphosphoryl substituent occupying an axial position. The latter adopts an almost syn-periplanar conformation around the P—C bond. The molecules form centrosymmetric dimers connected by O—H⋯O hydrogen bonds.