Geometry transformation of ionic surfactants and adsorption behavior on water/n-decane-interface: calculation by molecular dynamics simulation and DFT study

Understanding the effect of surfactant structure on their ability to modify interfacial properties is of great scientific and industrial interest. In this work, we have synthesized four amide based ionic surfactants under acidic or basic conditions, including CTHA·HCl, CTEA·HCl, CTHA⁻Na⁺ and CTEA⁻Na⁺. Experiments have proved that the anionic surfactant with polyethylene oxide groups (CTEA⁻Na⁺) had the lowest surface tension on the water/n-decane interface. Molecular dynamics simulations have been applied to investigate the structural effect on the adsorption behavior of four different surfactants. The surface tension, interface thickness, interface formation energy, density profiles, order parameters, radial distribution function on the water/n-decane interfaces were calculated and compared. During the equilibrium states, we found that the interface configuration of two cationic surfactants are almost linear while the two anionic surfactants are changed to bending shapes due to the different positions of the hydrophilic head groups. Further DFT study and wavefunction analysis of surfactants have shown that CTEA⁻Na⁺ can form stronger vdW interactions with n-decane molecules due to a more neutral electrostatic potential distribution. Meanwhile, the introduction of polyethylene oxide groups has offered more H-bonding sites and resulted in more concentrated H-bonding interactions with water molecules. The difference of weak interactions may contribute to the conformational change and finally affect the interface properties of these ionic surfactants.

The difference of weak interactions may contribute to the conformational change and finally affect the interface properties of these ionic surfactants.     

Conformational dynamics of superoxide dismutase (SOD1) in osmolytes: a molecular dynamics simulation study

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the misfolding of Cu, Zn superoxide dismutase (SOD1). Several earlier studies have shown that monomeric apo SOD1 undergoes significant local unfolding dynamics and is the predecessor for aggregation. Here, we have employed atomistic molecular dynamics (MD) simulations to study the structure and dynamics of monomeric apo and holo SOD1 in water, aqueous urea and aqueous urea–TMAO (trimethylamine oxide) solutions. Loop IV (zinc-binding loop) and loop VII (electrostatic loop) of holo SOD1 are considered as functionally important loops as they are responsible for the structural stability of holo SOD1. We found larger local unfolding of loop IV and VII of apo SOD1 as compared to holo SOD1 in water. Urea induced more unfolding in holo SOD1 than apo SOD1, whereas the stabilization of both the form of SOD1 was observed in ternary solution (i.e. water/urea/TMAO solution) but the extent of stabilization was higher in holo SOD1 than apo SOD1. The partially unfolded structures of apo SOD1 in water, urea and holo SOD1 in urea were identified by the exposure of the hydrophobic cores, which are highly dynamic and these may be the initial events of aggregation in SOD1. Our simulation studies support the formation of aggregates by means of the local unfolding of monomeric apo SOD1 as compared to holo SOD1 in water.

Change in conformations of apo and holo SOD1 in water and in osmolytes in terms of configurational entropy (S).     

Formation mechanism of bound rubber in elastomer nanocomposites: a molecular dynamics simulation study

Bound rubber plays a key role in the mechanical reinforcement of elastomer nanocomposites. In the present work, we reveal the formation mechanism of bound rubber in elastomer nanocomposites, using the coarse-grained molecular dynamics simulations. For the polymer–nanoparticle system, the “chain bridge” connected with neighboring nanoparticles forms, once the gap between two neighboring nanoparticles is less than the polymer size. The polymer–nanoparticle–solvent systems, mimicking the oil-swollen rubber in the experiment, are simulated with three models. From the analysis of the potential energy, the static structure and dynamic diffusing processes, all the models indicate that the increase of the volume fraction of the nanoparticles and the polymer−nanoparticle interaction strength could promote the formation of the bound rubber. The existence of solvent disrupts the bound rubber, and eventually deteriorates the mechanical properties. These simulations could provide some theoretical guidance for a better understanding of the formation mechanism of the bound rubber, which is helpful for designing the elastomer materials with excellent mechanical properties.

The formation mechanism of the bound rubber in elastomer nanocomposites using the coarse-grained molecular-dynamics simulations.     

The effect on ion channel of different protonation states of E90 in channelrhodopsin-2: a molecular dynamics simulation

Channelrhodopsin-2 (ChR2) is a cationic channel protein that has been extensively studied in optogenetics. The ion channel is opened via a series of proton transfers and H-bond changes during the photocycle but the detailed mechanism is still unknown. Molecular dynamics (MD) simulations with enhanced sampling were performed on the dark-adapted state (i.e., D470) and two photocycle intermediates (P₁⁵⁰⁰ and P₂³⁹⁰) to study the proton transfer path of the Schiff base and the subsequent conformational changes. The results suggest there are two possible proton transfer pathways from the Schiff base to proton acceptors (i.e., E123 or D253), depending on the protonation of E90. If E90 is protonated in the P₁⁵⁰⁰ state, the proton on the Schiff base will transfer to E123. The polyene chain of 13-cis retinal tilts and opens the channel that detours the blocking central gate (CG) and forms a narrow channel through the transmembrane helices (TM) 2, 3, 6 and 7. In contrast, if E90 deprotonates after retinal isomerization, the primary proton acceptor is D253, and an almost-open channel through TM1, 2, 3 and 7 is generated. The channel diameter is very close to the experimental value. The potential mean force (PMF) suggests that the free energy is extremely low for ions passing through this channel.

With E90 protonated, the proton acceptor of RSBH⁺ is E123 with a narrow channel along TM3; while with E90 deprotonated, proton transfer from RSBH⁺ to D253 generates an approximately open channel along TM2.     

Shedding light on the structural properties of lipid bilayers using molecular dynamics simulation: a review study

In recent years, a massive increase has been observed in the number of published articles describing accurate and reliable molecular dynamics simulations of lipid bilayers. This is due to several reasons, including the development of fast and efficient methods for treating long-range electrostatic interactions, significant progress in computer hardware, progress in atomistic simulation algorithms and the development of well-validated empirical molecular mechanical force fields. Although molecular dynamics is an effective approach for investigating different aspects of lipid bilayers, to the best of our knowledge, there is no review in the literature that explains the different analyses that can be carried out with membrane simulation. This review gives an overview about the some of the most important possible analyses, technical challenges, and existing protocols that can be performed on the biological membrane by molecular dynamics simulation. The reviewed analyses include the degree of membrane disruption, average area per lipid, probability distributions for the area per lipid molecule, membrane thickness, membrane area compressibility, lateral diffusion, rotational diffusion, order parameters, head group tilt, electron density profile, mass density profile, electrostatic potential profile, ordering of vicinity waters, number of hydrogen bonds, and radial distribution function.

This review gives an overview about the some of the most important possible analyzes, technical challenges, and existing protocols that can be performed on the biological membrane by the molecular dynamics simulation.     

Influence on ferric chloride aqueous solution caused by external electrostatic field: a molecular dynamics simulation study

A detailed analysis of structural properties and dynamic properties of ferric chloride aqueous solution under external electrostatic fields with different intensities was performed by molecular dynamics (MD) simulations. The effects on the ferric chloride aqueous solution caused by using an electrostatic field were examined in terms of the radial distribution function of the Fe³⁺ ion and water molecule/Cl⁻, coordination number of water/Cl⁻ around the Fe³⁺ ion, characteristics of hydrogen bonds, solution viscosity, and how these effects influence the hydrolysis process of the Fe³⁺ ion. The goal behind the study is to attain additional insights into the mechanism of electrocoagulation when ferric chloride is used as coagulant, and provide a fundamental basis for the practical use of this technology.

A detailed analysis of structural properties and dynamic properties of ferric chloride aqueous solution under external electrostatic fields with different intensities was performed by molecular dynamics (MD) simulations.     

Molecular dynamics simulation of four typical surfactants in aqueous solution

The thermodynamic values of the four surfactants, anionic surfactants, nonionic surfactants, zwitterion surfactants and gemini surfactants, were calculated by molecular dynamics simulation. The calculated results of thermodynamic parameters showed that the four surfactant can form micelles spontaneously. The mainly force for micellization process is entropy-driven, and as the temperature increases, the entropy-driven contribution is gradually reduced. There are linear enthalpy–entropy compensation phenomena for the four surfactants. Among the studied four surfactants, the gemini surfactant is the easiest to form micelles and has good stability, the zwitterion surfactant is the second, and the anionic surfactant is the least stable.

The thermodynamic values of the four surfactants, anionic surfactants, nonionic surfactants, zwitterion surfactants and gemini surfactants, were calculated by molecular dynamics simulation.     

Single-layer membranes for organic solvent nanofiltration: a molecular dynamics simulation and comparative experimental study

Organic solvents are widely used in pharmaceutical and chemical industries. Their separation and recovery account for a large part of energy consumption and capital cost in many industrial processes. MoS₂ membranes with varying pore sizes (0.6 nm pore with S atoms, 0.7 nm pore with Mo atoms, 1.3 nm pore with S atoms, 1.4 nm pore with Mo atoms) were investigated as organic solvent nanofiltration (OSN) membranes using molecular simulation in this study. The fluxes of five polar solvents (methanol, ethanol, propanol, acetonitrile and acetone) and a nonpolar solvent (n-hexane) were predicted. Although the 0.6 nm S pore has a smaller pore size, it has a better flux for some organic solvents than the 0.7 nm Mo pore. This selective behavior of molybdenum disulfide was confirmed by calculating the potential of mean force (PMF) of each solvent molecule. The PMFs show that polar solvents face a higher energy barrier through the pore, and greater resistance needs to be overcome. After testing the permeability of solvent by experiment and simulation, the flux changes of different solvents have the same trend in experiment and simulation. The solvent permeability was slightly affected in the presence of solute (acetaminophen), and MoS₂ membranes with small pores demonstrated 100% rejection rate for acetaminophen. This study confirmed that pore chemistry and pore size play important roles in OSN, and MoS₂ is a promising OSN membrane for the recovery of organic solvents.

Both simulated and experimental results demonstrated a good correlation between solvent permeances and solvent properties for the single-layer MoS₂ membrane.     

Unidirectional transport of water nanodroplets entrapped inside a nonparallel smooth surface: a molecular dynamics simulation study

The unidirectional transport of liquid nanodroplets is an important topic of research in the field of drug delivery, labs on chips, micro/nanofluidics, and water collection. Inspired by nature a nonparallel surface (NPS) is modelled in this study for pumpless water transport applications. The dynamics of water transport is analyzed with the aid of Molecular Dynamics (MD) simulations. There were five different types of NPSs namely A1, A2, A3, A4, and A5 utilized in this study, with separation angles equal to 5°, 7°, 9°, 11°, and 13° respectively. The water droplet was placed at the beginning of the open end of the NPS and it moved spontaneously towards the cusp of the surface in all cases except for the 13° NPS. The size of the water droplet, too, was altered and four different sizes of water droplets (3000, 4000, 5000, and 6000 molecules) were utilized in this study. Furthermore, the surface energy parameter of the NPS was also changed and four different values, i.e. 7.5 eV, 17.5 eV, 27.56 eV, 37.5 eV were assigned to the surface in order to represent a surface with hydrophobic to hydrophilic characteristics. In addition the importance of water bridge formation for its spontaneous propulsion with the influence of surface energy and droplet size is also discussed in this study. Moreover, a unique design is modelled for the practical application of water harvesting and a large size water droplet is formed by combining two water droplets placed inside a NPS.

Two water nanodroplets spontaneously move towards the cusp of nonparallel surfaces and coalesce to form a large size nanodroplet.     

Correction: Shedding light on the structural properties of lipid bilayers using molecular dynamics simulation: a review study

Correction for ‘Shedding light on the structural properties of lipid bilayers using molecular dynamics simulation: a review study’ by Sajad Moradi et al., RSC Adv., 2019, 9, 4644–4658.

The authors regret that incorrect details were given for ref. 22, 26 and 81 in the original article. The correct versions of ref. 22, 26 and 81 are given below.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

The effect of misclassification in screening trials: a simulation study

BACKGROUND: Misclassification of study endpoints in randomized clinical trials of screening tests has been well documented, yet its effect on study power, type I error rate, and risk ratio estimate have not been studied in depth. METHODS: We constructed a Markov model to depict the natural history of disease and the effect of screening on it. Using this model we simulated subjects in a two-arm RCT. We varied the type and amount of misclassification, and studied the effect on two endpoints--disease-specific mortality and the incidence of disease-specific symptoms. RESULTS: Failure to identify disease-specific events in a RCT of screening has a small effect on the risk ratio estimate and study power. In contrast, the false identification of events as being attributable to the target disease greatly reduces study power. CONCLUSIONS: Investigators of RCTs of screening tests should carefully consider the potential for misclassification and the type of misclassification that their study is as risk for. Studies should be designed to minimize misclassification. The effect of misclassification on power should be considered in sample size calculations.     

Molecular mechanism of the skin permeation enhancing effect of ethanol: a molecular dynamics study

Ethanol is widely used in various pharmaceutical and cosmetic formulations in order to enhance skin penetration of active ingredients. While it is well known that ethanol partitions into the skin and enhances the permeation of both polar and nonpolar molecules, the exact mechanisms by which it enhances skin permeability are not fully understood. Several mechanisms have been proposed including lipid extraction from the stratum corneum (SC), fluidisation of SC lipid bilayer, alteration of SC protein conformation and enhancement of the drug solubility in the SC lipids. In this study, we performed molecular dynamics (MD) simulations of SC lipid bilayers comprised of an equimolar mixture of ceramides, cholesterol and free fatty acid in the presence of aqueous mixtures of ethanol. Various unrestrained MD simulations were performed in the presence of aqueous ethanol solution at molar ratios (x) ranging from x = 0 to x = 1. It was found that ethanol enhances bilayer permeability by dual actions (a) extraction of the skin lipids and (b) enhancing the mobility of lipid chains. Ethanol''s permeation enhancing effect arises from its superior ability to form hydrogen bonds with headgroup atoms of skin lipids. Further, the free energy of extraction of ceramides (CER) and fatty acids (FFA) from the lipid bilayer was studied using umbrella sampling simulations. The free energy of extraction of CER was found to be much higher compared to FFA for all ethanol concentrations which shows that CER are difficult to extract as compared to FFA. Finally, the permeation of benzoic acid drug molecules through the skin lipid bilayer is shown in presence of ethanol molecules. It was found that ethanol selectively targets the FFA of the skin lipid bilayer and extracts it out of the lipid bilayer within few microseconds. Further, ethanol penetrates inside the lipid layer and creates the channels from which drug molecules can easily cross the lipid layer. Our observations (both in unrestrained and umbrella sampling simulations) are consistent with the experimental findings reported in the literature. The simulation methodology could be used for design and testing of permeation enhancers (acting on skin SC lipid lamella) for topical and transdermal drug delivery applications.

Concentration dependent action of mechanism of ethanol on skin SC lipid barrier.     

The effect of mutation in the stem of the MicroROSE thermometer on its thermosensing ability: insights from molecular dynamics simulation studies

A large number of bacteria have been found to govern virulence and heat shock responses using temperature sensing RNAs known as RNA thermometers (RNATs). They repress translation initiation by base pairing to the Shine–Dalgarno (SD) sequence at low temperature. Increasing the temperature induces the RNA duplex to unfold and expose the SD sequence for translation. A prime example is the ROSE thermometer module known to regulate the production of the ROSE heat shock protein in Bradyrhizobium japonicum. The unfolding of a 29-nucleotide long MicroROSE RNA element which forms a critical component encompassing the SD sequence, and three mutants that differ from it by deletion of a guanine nucleotide or mutations near the SD and stem regions have been studied using high temperature molecular dynamics simulations. The simulations reveal the progressive manner in which a biologically functional RNA thermometer unfolds. Our simulations reveal that deletion of the highly conserved G10 residue, opposite to the SD region leads to the formation of a stable RNA helix that has lost its thermosensing ability. Mutations of bases A5 → U5 and U25 → A25 near the stem increase the thermosensing ability due to the allosteric effect which leads to a global destabilization effect on the structure. The temperature-dependant regulation of this thermometer has been investigated by estimation of differences in the unfolding paths by calculating individual residue fluctuation, stacking energy, the contact map plot and the lifetime dynamics plot of non-Watson–Crick hydrogen bonds at three different temperatures. Results reveal that partial unfolding at higher temperature starts from the hairpin tetra loop end and terminates at the stem region through the SD associated region. Two canonical hydrogen bonds between U9–A22 and four non-canonical hydrogen bonds between G10–G21 and U6–U24 around the internal loop play an important role in partial melting of the RNA helix. These results demonstrate how small alterations in RNA structure can regulate gene expression and illuminate the molecular basis of the function of an important bacterial regulatory motif.

Mutation induced thermosensing ability of MicroROSE thermometer.     

Molecular dynamics simulation study of adsorption of anionic–nonionic surfactants at oil/water interfaces

Four anionic–nonionic surfactants with the same headgroups and different units of oxygen ethyl (EO) and oxygen propyl (PO) were adopted to investigate the influence on oil/water interfacial tensions in this article. Molecular dynamics (MD) simulations were conducted to study the interfacial property of the four surfactants. Four parameters were proposed to reveal the effecting mechanism of molecular structure on interfacial tension, which included the interfacial thickness, order parameter of the hydrophobic chain, radial distribution function, and the solvent accessible surface area. In addition, the electrostatic potential of the four surfactants was calculated. The research results indicated that the interface facial mask formed by the surfactants, which contained three EO or three PO units was more stable, and it was easier for the surfactants of six EO or six PO units to form a microemulsion at higher concentrations. The adsorption mechanism of the anionic–nonionic surfactant systems at the oil/water interfaces was supplemented at a molecular level, which provided fundamental guidance for an in-depth understanding of the optimal selection of the surfactants in enhancing oil recovery.

Four anionic–nonionic surfactants with the same headgroups and different units of oxygen ethyl (EO) and oxygen propyl (PO) were adopted to investigate the influence on oil/water interfacial tensions in this article.     

The transport of a charged peptide through carbon nanotubes under an external electric field: a molecular dynamics simulation

The study of interactions between biomolecules and carbon nanotubes (CNTs) is of great importance in CNT-based drug delivery systems and biomedical devices. In this work, the transport of polyarginine (R8) peptide through CNTs under an external electric field was investigated via all-atom molecular dynamics (AAMD) simulation. It was found that the electric field can assist the R8 peptide to overcome the resistance and make the transport smooth. Moreover, the efficiency of transport was improved with the increasing intensity of the electric field in a suitable range. In addition, we also investigated the effects of different types of CNTs on the transport of the R8 peptide and found that the single-walled carbon nanotube (SWCNT) was more suitable for transporting the R8 peptide than the double-walled carbon nanotube (DWCNT) due to its lower energy barrier to the R8 peptide. All these findings shed light on the role of the electric field on the transport of the R8 peptide through CNTs and also gave some valuable insights into the effects of CNT types on the transport process of the peptide.

The role of electric field and types of carbon nanotube influencing the delivery process of peptide through CNTs were studied via all-atom molecular dynamics simulation.     

The penetration of a charged peptide across a membrane under an external electric field: a coarse-grained molecular dynamics simulation

The processes of single polyarginine (R8) peptide penetration through planar and vesicle membranes under an external electric field are simulated via a coarse-grained molecular dynamics (CGMD) simulation. The results show that the external electric field can greatly enhance the penetration possibility of the R8 peptide through membranes. For different membranes (planar membrane and curved vesicle membrane), the amplitudes of electric fields needed for penetration are different. The penetration time of the R8 peptide across membranes decreases with the increasing amplitude of the external electric field applied. Under a constant electric field, the length of penetration time for different membranes is also different. For a better understanding of the mechanism of the penetration, we analyzed the Potential Mean Force (PMF) of the R8-membrane systems and found that the PMFs of the planar membrane and the curved vesicle membrane have a large difference. This may be one of the main factors that induces the different penetration processes of the R8 peptide across membranes when they respond to the same external electric field. All these findings shed light on the role of external electric field on the penetration of R8 peptide through membranes and also give some insights into the effects of membrane curvature on the transportation processes of the peptide carriers.

The processes of single polyarginine (R8) peptide penetration through planar and vesicle membranes under an external electric field are simulated via a coarse-grained molecular dynamics (CGMD) simulation.     

The liquid–amorphous phase transition,slow dynamics and dynamical heterogeneity for bulk iron: a molecular dynamics simulation

Based on molecular dynamics (MD) simulations, we investigate the liquid–amorphous phase transition, slow dynamic and dynamical heterogeneity (DH) for bulk iron in temperatures ranging 300–2300 K. The structure of obtained models is explored through the pair radial distribution function (PRDF) and simplex statistics. It was shown that the splitting of a PRDF second peak appears when the liquid transforms to an amorphous solid. This feature is originated from the transformation of simplexes from strongly-to weakly-distorted tetrahedron type. Further, we reveal that the diffusivity in the liquid is realized through the local density fluctuations (LDF) which are strongly correlated with each other. The diffusion coefficient is found to be a product of the rate of LDF act and mean square displacement of particles per LDF act. The later quantity mainly contributes to the slow dynamics and DH in the liquid. We found that the mobile atom clusters move during relaxation time, but mobile atoms do not tend to leave their cluster. Our work is expected to contribute a pathway to determine the liquid–amorphous phase transition and DH heterogeneity of bulk metal.

Based on molecular dynamics (MD) simulations, we investigate the liquid–amorphous phase transition, slow dynamic and dynamical heterogeneity (DH) for bulk iron in temperatures ranging 300–2300 K.     

Temperature dependence of the interfacial bonding characteristics of silica/styrene butadiene rubber composites: a molecular dynamics simulation study

Based on our previous studies on the modification of in-chain styrene butadiene rubber (SBR) using 3-mercaptopropionic acid as well as its composites filled with silica, we further constructed two types of models (amorphous and layered) to investigate the temperature dependence of the interfacial bonding characteristics of silica/SBR composites via molecular dynamics (MD) simulation. The competing effects of rubber–rubber interactions and filler–rubber interactions were identified, and the relationship between the competing effects and the temperature was determined. Besides this, the effect of temperature on the mobility and distribution of SBR chains on the surface of silica was investigated. It was found that the stronger the interfacial interactions, the less sensitive the motion of SBR chains to temperature. Finally, the number and length of hydrogen bonds as a function of temperature were analyzed. These simulated results deepened the understanding of interface temperature dependence of the silica/SBR composites and gave a molecular level explanation for the existence of an optimum modifier content (14.2 wt%) that is temperature independent.

Temperature dependence of the interface between silica and styrene butadiene rubber modified by 3-mercaptopropionic acid was investigated by molecular dynamics simulation.     

Bioinspired pressure-sensitive adhesive: evaluation of the effect of dopamine methacrylamide comonomer as a general property modifier using molecular dynamics simulation

The use of catechol-containing comonomers as a general property enhancer to achieve unique properties has received particular attention for designing bioinspired polymeric materials. In this study, molecular dynamics simulation was used to investigate the role of dopamine methacrylamide (DMA) and N-phenethyl methacrylamide (PMA) comonomers in chain conformation and their effects on the mechanical properties and adhesion of poly(n-butyl acrylate-co-acrylic acid) copolymer. Addition of 4% by weight of DMA comonomer in the terpolymer structure reduces the gyration radius of the poly(n-butyl acrylate-co-acrylic acid) copolymer. This reduction is due to the formation of intramolecular hydrogen bond interactions. A further increase in the DMA up to 12.2% by weight increases the radius of gyration by 5%. The effect of PMA on the gyration radius of the poly(n-butyl acrylate-co-acrylic acid) copolymer is more extensive, compared to DMA. While DMA enhances both van der Waals and electrostatic components of the cohesive energy density through increasing π–π interactions and hydrogen bond formations, PMA only improves the van der Waals component. Assessment of mechanical properties revealed that the addition of DMA comonomer resulted in a transition from brittle to tough behavior in poly(n-butyl acrylate-co-acrylic acid) pressure-sensitive adhesive. Ductility index improvement by DMA is higher than that by PMA. DMA comonomers accumulate on the silica surface resulting in the terpolymer chains approaching the dry silica surface from the hydroxyl groups of the catechol. Accumulation of DMA only enhances the cohesive energy and does not improve the adhesive energy.

The use of catechol-containing comonomers as a general property enhancer to achieve unique properties has received particular attention for designing bioinspired polymeric materials.     

The effect of porphyrins on cellular redox systems: a study on the dark effect of porphyrins on phagocytes

Abstract. Erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) are characterized by skin morbidity, induced by pro-inflammatory reactive oxygen species generated by the photosensitizing properties of protoporphyrin IX and uroporphyrin I. How these porphyrins exert a toxic effect on the liver in the absence of light is poorly understood. We tested the hypothesis that porphyrins can interference with cellular redox systems, by studying the dark effects of protoporphyrin (PP), haematoporphyrin (HP), deu-teroporphyrin (DP) and uroporphyrin (UP) on the cellular redox system of phagocytes, and on enzymatic oxyradical generating systems. Both in phagocytic cells and enzymatic systems, a dose-dependent inhibition of chemiluminescence was observed by all porphyrins added. Catalase and SOD-like activity of porphyrins was excluded by oxygraph and ferricyto-chrome c reduction. However, ferrocytochrome c oxidation was inhibited by porphyrins indicating ferrireductase-like activity. In a Fenton type reaction between H₂O₂ and PP, we could demonstrate the generation of *OH, or an electronically excited por-phyrin species. No influence on phagocyte chemotaxis, phagocytosis and killing-capacity was observed. We conclude that porphyrins do interfere with (cellular) redox systems and can both inhibit and enhance oxygen free radical generation, dependent on the type of redox reaction. Porphyrins can thus affect cellular metabolism. Since H₂O₂ and PP both readily dissolve in biological membranes, their interaction in the presence of transition metals may contribute to the toxic dark effects of porphyrins as observed in patients with EPP and PCT.