Bogumil Brzezinski

A proton pathway with large proton polarizability and the proton pumping mechanism in bacteriorhodopsin — Fourier transform difference spectra of photoproducts of bacteriorhodopsin and of its pentademethyl analogue

Abstract The first part of the photocycle of bacteriorhodopsin (BR) (BR 570 , K 630 , L 550 and M 412 ) is studied by difference Fourier transform-infrared (FT-IR) spectroscopy. These results are compared with the respective difference spectra of the pentademethyl analogue (BR a ). With the BR intermediates, the same bands are observed as in previous studies. This is especially true in the carbonyl region. With BR a , however, the behaviour of the intermediates is different from the respective intermediates of BR. The photocycle is interrupted before the L state and returns to BR a . In the case of BR, in the K intermediate, a very broad band is observed in the region 2800-2200 cm −1 . In the L intermediate, a continuous absorption is observed beginning at 2800 cm −1 and extending toward smaller wavenumbers over the whole region studied. This continuum vanishes with the formation of the M 412 intermediate and, instead, two very broad bands are found in the region 2700-2200 cm −1 . The broad band in the K state indicates that at least one strong hydrogen bond is formed in which the proton is not well localized. From the continuum observed in the L intermediate, it is concluded that a hydrogen-bonded chain is formed showing large proton polarizability caused by collective proton motion. This chain is discussed on the basis of a structural model based on literature data. The Schiff base—Asp 85 and Tyr 185—Asp 212 bonds show proton polarizability. With the transition to the intermediate M 412 , within both hydrogen bonds, the protons are shifted within these hydrogen bonds to Asp 85 and Asp 212, due to changes of the local electrical fields and to specific interactions arising due to conformational changes of the protein. In this way the negative charges in the neighbourhood of Arg 82 are neutralized and hence the proton potential at Arg 82 raised. Thus, the positive charge is shifted to the outside of the proton channel and released to the bulk water phase. The continuum is no longer observed in M 412 since the proton potentials in the chain are now asymmetrical. Hence, in the M 412 intermediate only broad bands are found, indicating strong but asymmetrical hydrogen bonds present in the active centre.

Spectroscopic studies and PM5 semiempirical calculations of new Schiff bases of gossypol with amino derivatives of crown ethers

Abstract Two Schiffs bases of racemic gossypol with amino derivatives of crown ethers were synthesised and studied by FT-IR and 1 H NMR spectroscopy, while their structures were calculated by the PM5 semiempirical method. These studied Schiffs bases exist in the solid state and in solutions as enamine forms. In the solid state the interactions between OH groups in the 6, 6′ positions and oxygen atoms of the crowns are dependent on the crown size whereas in solutions they are not. These interactions are very well evidenced in the FT-IR and 1 H NMR spectra. In the 1 H NMR spectra the existence of two enantiomers of the Schiffs bases are well visible. The structures of the Schiffs bases and the strength of the hydrogen bonds within these structures are discussed.

Synthesis, cytotoxicity and antibacterial activity of new esters of polyether antibiotic – salinomycin

A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.

Synthesis and antimicrobial properties of monensin A esters.

The esters (2-10) of the ionophore antibiotic Monensin (1) were synthesized by four different methods, which are discussed in detail. These new esters were characterized by various spectroscopic techniques and subsequently tested in the face of their antimicrobial properties. Three derivatives (3, 8 and 10) showed activity against Gram-positive bacteria. Additionally derivative (10) exhibited a relatively low antifungal activity against Candida in contrast to Monensin A.

FTIR, NMR and kinetic studies of proton transfer reactions from nitro-substituted diarylmethanes to N-bases with guanidine character

Abstract Deprotonation of bis(2,4-dinitrophenyl)methane (C-acid 1) and 2,4-dinitrophenyl-2,4,6-trinitrophenylmethane (C-acid 2) by 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene (MTBD) and 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) in acetonitrile has been studied using 1 H and 13 C NMR as well as FT-IR spectroscopy. The 1:1 mixtures of N-bases with C-acids form protonated N-bases and products, for which only one respective structure was found. In the case of deprotonated C-acid 1 a symmetrical charge distribution in the phenyl rings was found, whereas for deprotonated C-acid 2 the charge distribution was asymmetrical. The spectral feature was explained as a strong electrostatic interaction between the product and the protonated N-bases. The kinetics of the proton transfer reaction from C-acid 1 and C-acid 2 to MTBD and TBD in acetonitrile are reported. The activation parameters are discussed in two aspects: the steric effect of the basic centre and the delocalization of charge for the carbanion products.

Antiproliferative activity of salinomycin and its derivatives.

Antiproliferative activity of seven amides and one benzotriazole ester derivative of salinomycin, a polyether ionophore antibiotic, with recently reported antibacterial activity, are herein described. Salinomycin and the majority of derivatives exhibit potent antiproliferative activity against the drug-resistant cancer cell lines. Moreover almost all derivatives show stronger activity against LoVo/DX cell line than that of unmodified salinomycin.

Homoconjugated hydrogen bonds with amidine and guanidine bases Osmometric, potentiometric and FTIR studies

Five very strong N bases, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), pK a =23.4; 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),pK a =23.9; tetramethylguanidine (TMG), pK a =23.3; 2-phenyl-tetramethylguanidine (PhTMG), pK a =20.6; and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), pK a =24.97; have been studied by osmometric measurements which showed that they are monomeric in acetonitrile solutions. The constants of the formation of homoconjugated complexes were determined by potentiometric measurements. In the IR spectra of the semi-protonated complexes of DBN, DBU and TMG, the homoconjugated N + –H···NN ···H– + N hydrogen bonds cause broad band complexes in the region 3200–2500 cm -1 instead of the expected continua. This spectral peculiarity is discussed.

Spectroscopic study and PM5 semiempirical calculations of tautomeric forms of gossypol Schiff base with n-butylamine in the solid state and in the solution

Abstract The Schiff base of gossypol with n -butylamine was synthesised and its structure was studied by FT-IR and 1 H NMR, 13 C NMR and 15 N NMR as well as PM5 semiempirical methods. It is shown that the Schiff base exists in solution and in solid state as the enamine–enamine tautomer. The structure of this tautomer is discussed in detail.

Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic-salinomycin.

For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic-salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide derivatives have been screened for their in vitro antimicrobial activity against the typical gram-positive cocci, gram-negative rods and yeast-like organisms, as well as against a series of clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus. Amides of salinomycin have been found to show a wide range of activities, from inactive at 256 μg/mL to active with MIC of 2 μg/mL, comparable with salinomycin. As a result, phenyl amide (3b) was found to be the most active salinomycin derivative against gram-positive bacteria, MRSA and MSSA.

Proton polarizability of intramolecular hydrogen bonds with molecules non-conjugated and conjugated between donor and acceptor groups

Abstract Compounds with intramolecular hydrogen bonds are investigated. When the hydrogen-bond donor and acceptor groups are not electronically conjugated, IR continua indicate a large proton polarizability. When they are conjugated the continua are very weak. Thus not only the proton potential but also the dependence of the dipole moment on the vibrational coordinate is decisive for occurrence of the continua.