Cationic Amino Research Articles

Molecular modeling of SWR-0342SA, a β 3-selective agonist, with β 1- and β 3-adrenoceptor

The molecular dynamics (MD) simulations study in the formation of the complex between compound SWR-0342SA and β-ARs suggested that upon binding SWR-0342SA stimulates receptor activation through residues network (Asp104, Leu335 in β 1-AR; Asp117, Ser209, Leu303, Ser191 in β 3-AR) in an active conformation state. The models suggest that the structural origin of the selectivity of SWR-0342SA to β 3-AR vs. β 1-AR comes from the following results: (a) the tight interaction between the agonist and the TMs 3, 5, 6 and 2 nd EC loop. Asp117 interacts with the cationic amino group of the agonist molecule. (b) Additional contacts are done with Ser209, Leu303 and Ser191. These results are in good agreement with the binding affinities (pKi values) of SWR-0342SA to β-AR family expressed in recombinant mammalian cells.

Crystal and molecular structure of nitraminotetrazoles and nitramino-1,2,4-triazoles. V. 5-nitraminotetrazole methylammonium salt

An X-ray study was performed to investigate the structure of 5-nitraminotetrazole methylammonium salt. Monoclinic crystals, space group P21/n; a = 6.541(2) A, b = 19.157(4) A, c = 10.726(2) A; β = 96.24(2)°; V = 1336.07(1) A3; Z = 8, ρcalc = 1.602 g/cm3. The crystal structure has anions and cations of two independent types with close geometrical parameters. The anions are planar and have a nitrimine structure with an intramolecular hydrogen bond. All hydrogen atoms of the cationic amino groups form hydrogen bonds to the oxygen and nitrogen atoms of the anions. The negative charge is delocalized to different extents in the anions.

Optical tracking of organically modified silica nanoparticles as DNA carriers: A nonviral, nanomedicine approach for gene delivery

This article reports a multidisciplinary approach to produce fluorescently labeled organically modified silica nanoparticles as a nonviral vector for gene delivery and biophotonics methods to optically monitor intracellular trafficking and gene transfection. Highly monodispersed, stable aqueous suspensions of organically modified silica nanoparticles, encapsulating fluorescent dyes and surface functionalized by cationic-amino groups, are produced by micellar nanochemistry. Gel-electrophoresis studies reveal that the particles efficiently complex with DNA and protect it from enzymatic digestion of DNase 1. The electrostatic binding of DNA onto the surface of the nanoparticles, due to positively charged amino groups, is also shown by intercalating an appropriate dye into the DNA and observing the Forster (fluorescence) resonance energy transfer between the dye (energy donor) intercalated in DNA on the surface of nanoparticles and a second dye (energy acceptor) inside the nanoparticles. Imaging by fluorescence confocal microscopy shows that cells efficiently take up the nanoparticles in vitro in the cytoplasm, and the nanoparticles deliver DNA to the nucleus. The use of plasmid encoding enhanced GFP allowed us to demonstrate the process of gene transfection in cultured cells. Our work shows that the nanomedicine approach, with nanoparticles acting as a drug-delivery platform combining multiple optical and other types of probes, provides a promising direction for targeted therapy with enhanced efficacy as well as for real-time monitoring of drug action.

Cationic phosphoramidate alpha-oligonucleotides efficiently target single-stranded DNA and RNA and inhibit hepatitis C virus IRES-mediated translation.

A potential means to improve the efficacy of steric-blocking antisense oligonucleotides (ON) is to increase their affinity for a target RNA. The grafting of cationic amino groups to the backbone of the ON is one way to achieve this, as it reduces the electrostatic repulsion between the ON and its target. We have examined the duplex stabilising effects of introducing cationic phosphoramidate internucleoside linkages into ON with a non-natural alpha-anomeric configuration. Cationic alpha-ON bound with high affinity to single-stranded DNA and RNA targets. Duplex stabilisation was proportional to the number of cationic modifications, with fully cationic ON having particularly high thermal stability. The average stabilisation was greatly increased at low ionic strength. The duplex formed between cationic alpha-ON and their RNA targets were not substrates for RNase H. The penalty in T(m) inflicted by a single mismatch, however, was high; suggesting that they are well suited as sequence-specific, steric-blocking, antisense agents. Using a well-described target sequence in the internal ribosome entry site of the human hepatitis C virus, we have confirmed this potential in a cell-free translation assay as well as in a whole cell assay. Interestingly, no vectorisation was necessary for the cationic alpha-ON in cell culture.

Two new β-octamolybdate supported rare earth metal complexes: [NH 4] 2[{Gd(DMF) 7} 2(β-Mo 8O 26)][β-Mo 8O 26] and [NH 4][La(DMF) 7(β-Mo 8O 26)

Two novel β-octamolybdate supported rare earth metal complexes, [NH 4] 2[{Gd(DMF) 7(β-Mo 8O 26)}][β-Mo 8O 26] 1 and [NH 4][La(DMF) 7(β-Mo 8O 26)] 2, were obtained from the reaction of (NH 4) 6Mo 7O 24·4H 2O with LnCl 3 (Ln=Gd for 1 and La for 2) at low pH values in the mixed solvents of H 2O/DMF or H 2O/DMF/CH 3CN. The single X-ray diffraction studies reveal that 1 consists of discrete centrosymmetric heterometallic decanuclear [{Gd(DMF) 7} 2-β-Mo 8O 26] 2+, [β-Mo 8O 26] 4− and two amino cations. In each decanuclear [{Gd(DMF) 7} 2-β-Mo 8O 26] 2+ cation, the β-octamolybdate moiety is linked to two eight-coordinated Gd III cations, which is coordinated by seven DMF ligands and one terminal oxygen atom of molybdenum center. Compound 2 is built up from DMF coordinated La III fragment and β-octamolybdate unit joined together through two terminal oxygen atoms of two molybdenum atoms. Ferromagnetic behavior is observed for 1 from the magnetic measurement, which might result from the exchange interaction through the bridging β-[Mo 8O 26] 4− ligand or the presence of zero-field splitting.

Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor.

The histamine H4 receptor is a novel G-protein-coupled receptor with a unique pharmacological profile. The distribution of H4 mRNA suggests that it may play a role in the regulation of immune function, particularly with respect to allergy and asthma. To define the histamine-binding site of this receptor, molecular modeling and site-directed mutagenesis were used to predict and alter amino acids residing in the histamine-binding pocket. The effects of these alterations on histamine binding and receptor activation were then assessed. Our results indicate that Asp94 (3.32) in transmembrane region (TM) 3 and Glu182 (5.46) in TM5 are critically involved in histamine binding. Asp94 probably serves as a counter-anion to the cationic amino group of histamine, whereas Glu182 (5.46) interacts with the N(tau) nitrogen atom of the histamine imidazole ring via an ion pair. In contrast, Thr178 (5.42) and Ser179 (5.43) in TM5 are not significantly involved in either histamine binding or receptor activation. These results resemble those for the analogous residues in the H1 histamine receptor but contrast with findings regarding the H2 histamine receptor. Our results also demonstrate that Asn147 (4.57) in TM4 and Ser320 (6.52) in TM6 play a role in receptor activation but are not involved in histamine binding. Taken together, these data indicate that although histamine seems to bind to the H4 receptor in a fashion similar to that predicted for the other histamine receptor subtypes, there are also important differences that can probably be exploited for the discovery of novel H4-selective compounds.

Free radical degradation of chitosan with potassium persulfate

A thermal dissociation initiator, potassium persulfate (KPS), is added to the chitosan solution at 70 °C; immediately, the solution viscosity and the molecular weight of chitosan decrease in a very short time. Size exclusion chromatography, nuclear magnetic resonance and electron spin resonance were used to study the degradation mechanism. A free radical degradation mechanism of chitosan by KPS is then proposed. When KPS is thermally dissociated into anionic radicals, they are attracted to the cationic amino group in the chitosan ring. Subsequently, the anionic radical attacks the C-4 carbon and transfers the radical to the C-4 carbon by subtracting the hydrogen from it. The presence of free radical at C-4 carbon eventually results in the breakage of the glycosidic C–O–C bond in the chitosan main chain. According to this mechanism, the concentrations of KPS, total free radicals and the degraded chitosan chain at different degradation times are all calculated by solving the rate equations. Finally, the calculated average molecular weights of the degraded chitosan chains at different reaction times agree with the experimental values.

Adsorption of Sulforhodamine Dyes in Cationic Langmuir−Blodgett Films: Spectroscopic and Structural Studies

This paper reports the incorporation of sulforhodamine B (SRB) in the octadecylamine Langmuir−Blodgett (LB) films and the adsorbability of the cationic LB films have been investigated. It was observed that the adsorption process mainly occurred due to the ionic interaction between the cationic amino group of the long-chain amine and the sulfonic group of the SRB dye. Surface pressure−area isotherm studies confirmed the strong interaction between the long-chain amine and the SRB dye and the change of orientation of the molecules were observed with variation of pH of the subphase. Absorption, steady-state and ultrafast time-resolved fluorescence spectroscopic studies suggested the presence of the monomer and dimer of the SRB molecule in the restricted geometry of LB films. Furthermore, the contents of the monomer and dimer depend on the concentration of the dye and the adsorption process. The orientation of the SRB dye molecule in the LB films determined by polarized absorption spectra indicated a lying-flat orientation of the SRB molecule. Structural characteristics of the LB films such as orientation, layer−layer distance, and topography of the film surface have been investigated by FTIR spectroscopy, low-angle X-ray diffraction, and atomic force microscopy (AFM). Our preliminary results imply that the functional molecules in LB films are incorporated with a desired orientation by means of designing the molecular structure of the adsorbates.

Multilayer Assemblies of Tungstodiphosphate Anions on 1,7-Diaminoheptane Modified Glassy Carbon Electrode and the Electrocatalytic Reduction to Iodate

1,7-Diaminoheptane (DAH) had been covalently grafted on glassy carbon electrode by amino cation radical formation, which resulted in a stable cationic monolayer under proper pH conditions. Dawson-type tungstodiphosphate anion, P2W18O626– and small molecule, Ru(NH3)63+ were alternately assembled on the DAH modified electrode through layer-by-layer electrostatic interaction. Thus-prepared multilayer film had been characterized by cyclic voltammetry and X-ray photoelectron spectroscopy. The P2W18O626– multilayers exhibit high electrocatalytic response and sensitivity towards the reduction of iodate. With the increase of the number of P2W18O626– layers, the catalytic current was enhanced and the catalytic potential shifted positively. Iodate in table salt was determined at the modified electrode containing three layers of P2W18O626– with satisfactory results. The multilayer electrode is promising as an electrochemical sensor for the detection of trace iodate.

Metal ligand aromatic cation-pi interactions in metalloproteins: ligands coordinated to metal interact with aromatic residues.

Cation-pi interactions between aromatic residues and cationic amino groups in side chains and have been recognized as noncovalent bonding interactions relevant for molecular recognition and for stabilization and definition of the native structure of proteins. We propose a novel type of cation-pi interaction in metalloproteins; namely interaction between ligands coordinated to a metal cation--which gain positive charge from the metal--and aromatic groups in amino acid side chains. Investigation of crystal structures of metalloproteins in the Protein Data Bank (PDB) has revealed that there exist quite a number of metalloproteins in which aromatic rings of phenylalanine, tyrosine, and tryptophan are situated close to a metal center interacting with coordinated ligands. Among these ligands are amino acids such as asparagine, aspartate, glutamate, histidine, and threonine, but also water and substrates like ethanol. These interactions play a role in the stability and conformation of metalloproteins, and in some cases may also be directly involved in the mechanism of enzymatic reactions, which occur at the metal center. For the enzyme superoxide dismutase, we used quantum chemical computation to calculate that Trp163 has an interaction energy of 10.09 kcal mol(-1) with the ligands coordinated to iron.

Grafting of diaminoalkane on glassy carbon surface and its functionalization

Diaminoalkanes (NH 2(CH 2) n NH 2, n=7,10,12) were grafted onto a glassy carbon electrode (GCE) surface by amino cation radical formed during electrooxidation of amino group. The presence of diamine grafted layer at the GCE is demonstrated by X-ray photoelectron spectroscopy. The effect of the grafted layer at the GCE surface on the redox responses of Ru(NH 3) 6 3+ and Fe(CN) 6 3− redox probes has been investigated. Electrochemical impedance experiments indicate that the kinetics of electron transfer are slowed down when the scan rate taken to modify the GCE is low, and that diaminoalkane with longer alkyl-chain used has higher blocking characteristics. The amine-functionalized GCE is versatile not only to further covalently immobilize ferrocene acetic acid via carbodiimide coupling, but also as a charge-rich substrate to successfully adsorb heteropolyanion P 2W 18 in acidic solution by electrostatic interaction.

Layer-by-layer assembly of multilayer films consisting of silicotungstate and a cationic redox polymer on 4-aminobenzoic acid modified glassy carbon electrode and their electrocatalytic effects

A novel 4-aminobenzoic acid (4-ABA) monolayer film is formed on glassy carbon electrode (GCE) by amino cation radical method. Silicotungstic heteropolyanion (SiW 12O 40 4−, denoted as SiW 12)-containing multilayer films have been fabricated on the 4-ABA modified GCE surface by alternate deposition with a quaternized poly(4-vinylpyridine) partially complexed with [Os(bpy) 2Cl] 2+/+ (denoted as QPVP-Os). Cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS) and X-ray reflectivity (XR) have been used to characterise the as-prepared multilayer films. It is proved that the multilayer films are uniform and stable. The average thickness for a bilayer of QPVP-Os/SiW 12 in the multilayer film is 30.2 Å. The electrocatalytic activities of the multilayer films have been investigated on the reduction of three substrates of important analytical interests, HNO 2, BrO 3 − and H 2O 2. Especially, the influence of layer number of the multilayer films on the electrocatalytic reduction of HNO 2 has been investigated in detail.

Identification of Residues Involved in Substrate Recognition by a Vesicular Monoamine Transporter

To identify the residues involved in substrate recognition by recently cloned vesicular monoamine transporters (VMAT1 and VMAT2), we have mutagenized the conserved residues in a cytoplasmic loop between transmembrane domains two and three of VMAT2. Although studies of related bacterial antibiotic resistance proteins indicate an important functional role for this region, we found no effect of these mutations on VMAT2 activity. However, replacement of aspartate 33 in the first predicted transmembrane domain with an asparagine (D33N) eliminates transport. D33N shows normal levels of expression and normal binding at equilibrium to the potent inhibitor reserpine. However, in contrast to wild-type VMAT2, serotonin inhibits reserpine binding to D33N very poorly, indicating a specific defect in substrate recognition. Replacement of three serine residues in transmembrane domain three with alanine (Stmd3A) shows a similarly selective but even more profound defect in substrate recognition. The results suggest that by analogy to receptors and plasma membrane transporters for monoamines, the cationic amino group of the ligand interacts with an asparte in the first transmembrane domain of VMAT2 and hydroxyl groups on the catechol or indole ring interact with a group of serines in the third transmembrane domain. Importantly, D33N and Stmd3A retain coupling to the proton electrochemical gradient as measured by the delta microH(+)-induced acceleration of reserpine binding. This indicates that substrate recognition can be separated from coupling to the driving force.

Hydrogen bonding between aromatics and cationic amino groups

The proximity of cationic amino groups to aromatic rings in proteins as a motif has been used to interpret specificity, structural and conformational stability, and even catalytic activity in biological systems. To quantify these interactions, ammonium cation-aromatic ring complexes have been geometry-optimized using the 3-21G basis set at the Hartree-Fock level. Final binding energies are obtained from single-point RHF and MP2/6-31G * level calculations at the 3-21G optimized geometries. The cation species include NH 4 +, CH 3NH 3 +, and (CH 3) 4N +, and the aromatic systems (models for amino acid side-chains) consist of benzene, toluene (phenylalanine), paramethylphenol (tyrosine) and 4-methylindole (tryptophan). Twenty-five distinct complex geometries are obtained which can be represented by ten generic structures. The MP2 binding energies at the 3-21G optimized geometries compare very well with experiment. Special binding sites at the electronegative atoms (oxygen in paramethylphenol and nitrogen in 4-methylindole) are also found. The effect of basis set and theoretical level on the calculated results is tested and discussed. A reduced variational space binding energy component analysis of the ammonium-benzene complex shows the binding energy to have similar contributions from electrostatic (including exchange repulsion), polarization, and charge transfer terms. Comparison with potassium ion/ benzene shows similar binding energy but significantly different binding energy components.

Formation and characterization of neutral and cationic amino(thio)carbene complexes of gold(I) from thiazolyl precursors

Benzothiazole-2-yl-, 4-methylthiazolyl- and thiazolyl-lithium reacted with [AuCl(tht)](tht = tetrahydrothiophene) to form bis(thiazolyl)aurate compounds which can be protonated or alkylated to give mono- and bis-(carbene) complexes of the type [Au([graphic omitted])([graphic omitted])] and [Au(CNRCX1= CX2S)2]+(X1X2= C4H4; X1= Me, X2= H; X1= X2= H; R = H or Me). The strongly ligated gold phosphine and perfluorophenyl complexes [AuCl(PPh3)] and [Au(C6F5)(tht)] as well as AuCN also reacted with the thiazolyllithiums to afford, upon protonation or alkylation, cationic and neutral carbene compounds. Complicating side-reactions, such as homoleptic rearrangement, protonation or alkylation on carbon rather than nitrogen and dissociative polymerization were observed. The crystal structure of the neutral mono(carbene) complex [Au([graphic omitted])([graphic omitted])] shows a gold–gold interaction with a distance of 3.075(1)A.

Chemistry of [Ru 3O 2(NH 3) 14]Cl 6 (ruthenium red) intercalated in a smectite clay: thermal behaviour, reactivity with CO and CO/H 2, catalytic activity

The trimeric ruthenium amino cation ruthenium red was readily and quantitatively exchanged in a sodium bentonite. The multiply-charged ruthenium ions act as crosslinking molecular rods and induce a clay layer separation of ≈ 5 Å. The chemical modification of the intercalated species by thermal treatment was studied by IR and UV spectroscopy. The modification of the clay spacing was monitored by X-ray diffraction and surface area measurements. The catalytic activity of the clay for the vapour phase CO hydrogenation and hydroformylation of ethylene and propene was tested in a flow reactor at atmospheric pressure.

Geochemistry of Dissolved Organic Nutrients in Water Percolating through a Forest Ecosystem

AbstractDissolved organic matter (DOM) is a major vehicle for the translocation and loss of N and P from forest ecosystems. The chemical properties of DOM and its interactions with soil surfaces are crucial in determining the mobility of these organic nutrients. We fractionated DOM from throughfall, all soil horizons (Ultisols and Inceptisols), and stream water from an Appalachian mountain forest ecosystem into hydrophobic or hydrophilic acids, neutrals, and bases. We analyzed each fraction for dissolved organic C (DOC), N (DON), and P (DOP). Most of the DOC was in the acid fractions, with the humic fractions (hydrophobic acids and phenols) comprising 35 to 57% of the DOC in all samples except summer throughfall. Concentrations of all fractions declined with depth in the soil. As a percent of total DOC, the humics declined with depth, whereas the hydrophilic neutrals increased. Bases, which we expected to contain cationic amino groups, were < 2.5% of the DOC. Instead, most DON was in the humic, hydrophilic acid, and hydrophilic neutral fractions. Most DOP occurred in the hydrophilic acid, humic, and hydrophilic neutral fractions. The functional groups in which N and P occur had little influence on the behavior of most of the DOM as a whole since: (i) cationic DOM was such a minor component, and (ii) P was simply too rare to influence the anionic behavior of many molecules. Nevertheless, for those molecules in which P did occur, P may have influenced their behavior since a large percentage of the DOP was in the hydrophilic acid (i.e., anionic) fraction. The carboxylic and phenolic functional groups, or in some cases the neutrality, of the DOM molecules appeared to be much more important than N‐containing groups in influencing the behavior of the N carried passively by the DOM.

The Effect of Different Methods of Cationisation on the Starch Granule and Its Gelatinisation Product

AbstractThe effect on the form and structure of starch granules caused by cationisation using a solvent, by dry cationisation and by cationisation in a water slurry has been studied by means of scanning electron microscopy (SEM). By means of energy‐dispersive X‐ray analysis (EDXA) and electron spectroscopy (ESCA) analyses have been made of the chemical elements in the surface layer and inner part of the cationised granules and in gelatinised products prepared from the cationised granules.Cationisation does not change the form of the granules. In granules cationised in a water slurry a slight swelling can be observed. Cationisation gives the starch granules a thin shell‐like outer surface. In the case of solvent‐cationised and especially of dry‐cationised granules there are abundant quantities of small particles in the surface of the granules. These are the remains of chemicals added during cationisation.The ESCA analyses show that the amount of N in the surface layer of solvent‐cationised, dry cationised and water‐cationised granules studied is 3.1, 0.71 and 0.37% (w/w), respectively. In the gelatinised samples prepared from the cationised granules the amount of N in solvent‐ and water‐cationised granules is the same but in dry‐cationised granules it is only half as much, i.e. 0.35% (w/w).The amount of Cl in the surface layer is for solvent‐, dry‐ and water‐cationised granules 88, 47 and 21% of the N content, respectively. The Cl content in the gelatinised products of solvent‐ and water‐cationised granules is approximately the same as before gelatinisation but in the dry‐cationised product it is 50% less.Judging from the analyses it would seem that the cationic amino groups are evenly distributed throughout the granule in the case of solvent‐ and water‐cationised granules. In dry‐cationised granules, however, these groups are concentrated to starch molecules in the outer part of the granule.The significance from the paper‐manufacturing viewpoint of even distribution of the cationic groups throughout the granule, of a low Cl content and of the existence of remains of chemicals in cationic starch is briefly addressed.

The luminal K+ channel of the thick ascending limb of Henle's loop

In vitro perfused rat thick ascending limbs of Henle's loop (TAL) were used (n = 260) to analyse the conductance properties of the luminal membrane applying the patch-clamp technique. Medullary (mTAL) and cortical (cTAL) tubule segments were dissected and perfused in vitro. The free end of the tubule was held and immobilized at one edge by a holding pipette kept under continuous suction. A micropositioner was used to insert a patch pipette into the lumen, and a gigaohm seal with the luminal membrane was achieved in 455 instances out of considerably more trials. In approximately 20% of all gigaohm seals recordings of single ionic channels were obtained. We have identified only one single type of K+ channel in these cell-attached and cell-excised recordings. In the cell-attached configuration with KCl or NaCl in the pipette, the channel had a conductance of 60 +/- 6 pS (n = 24) and 31 +/- 7 pS (n = 4) respectively. In cell-free patches with KCl either in the patch pipette or in the bath and with a Ringer-type solution (NaCl) on the opposite side the conductance was 72 +/- 4 pS (n = 37) at a clamp voltage of 0 mV. The permeability was 0.33 +/- 0.02 . 10(-12) cm3/s. The selectivity sequence of this channel was: K+ = Rb+ = NH4+ = Cs+ greater than Li+ much greater than Na+ = 0; the conductance sequence was K+ much greater than Li+ much greater than Rb+ = Cs+ = NH4+ = Na+ = 0. In excised patches Rb+, Cs+ and NH4+ when present in the bath at 145 mmol/l all inhibited K+ currents out of the pipette. The channel kinetics were described by one open (9.5 +/- 1.5 ms, n = 18) and by two closed (1.4 +/- 0.1 and 14 +/- 2 ms) time constants. The open probability of this channel was increased by depolarization. The channel open probability was reduced voltage dependently by Ba2+ (half maximal inhibition at 0 mV: 0.07 mmol/l) from the cytosolic side. Verapamil, diltiazem, quinine and quinidine inhibited at approximately 1 mumol/l -0.1 mmol/l from either side. Similarly, the amino cations lidocaine, tetraethylammonium and choline inhibited at 10-100 mmol/l. The channel was downregulated in its open probability by cytosolic Ca2+ activities greater than 10(-7) mol/l and by adenosine triphosphate greater than or equal to 10(-4) mol/l. The open probability was downregulated by decreasing cytosolic pH (2-fold by a decrease in pH by less than or equal to 0.2 units).(ABSTRACT TRUNCATED AT 400 WORDS)

Cytotoxic effects of methionine alkyl esters and amides in normal and neoplastic cell lines.

Homologous series of L-methionine alkyl ester hydrochlorides and tosylates were synthesized and evaluated for in vitro growth inhibitory activity in Meth A sarcoma. Cytotoxicity, as determined by [3H]thymidine incorporation, was found to be directly proportional to alkyl chain length and surface tension lowering activity. L-Methionine decyl and dodecyl ester hydrochlorides possessed optimum cytotoxic activity (IC50 = 29, 28 microM) which was not reversible by the addition of L-methionine. Surface tension of a 50 microM solution of the decyl and dodecyl ester hydrochlorides were 35.4 and 32.7 dyn/cm, respectively. The corresponding decyl and dodecyl ester tosylates and amide hydrochlorides were less active. The N-t-butoxycarbonyl analogues were essentially inactive, demonstrating the necessity of an unsubstituted and/or potentially cationic amino group. Methionine dependence characteristics and cytotoxicity were also determined for three human (IMR-90, LX-1, MCF7) and four additional murine (L1210, L5178Y, 3T3, SV-T2) cell lines. The human cell lines Meth A, LX-1, and SV-T2 were found to be methionine independent. The LX-1 tumor cell line and the SV-T2 transformed line exhibited two to four times more sensitivity to the cytotoxic and cytolytic properties of the decyl and dodecyl ester hydrochlorides than their normal counterparts. The dodecyl amide hydrochloride derivative demonstrated enhanced cytotoxic activity in vivo relative to the corresponding ester, possibly due to decreased metabolic hydrolysis.