Key-lock Mechanism Research Articles

Drug delivery strategies for porphyrin-based photosensitizers in photodynamic antimicrobial chemotherapy

In the face of increasing antimicrobial resistance (AMR) and the looming threat of a return to a pre-antibiotics era, the exploration of alternative antimicrobial strategies becomes imperative. Among these, Photodynamic Antimicrobial Chemotherapy (PACT) stands out as a promising solution due to its multi-target principle, diverging from the key-lock mechanism inherent in conventional antibiotics. However, the hydrophobic nature, non-targeted distribution, stability issues, and limited tissue penetration of photosensitizers (PSs), particularly the extensively studied porphyrin-based compounds, pose structural limitations impacting their bioavailability and effective delivery to target sites. Therefore, various delivery strategies are adopted to improve their effectiveness in PACT. This includes attaching the PS to a variety of delivery vehicles such as nanoparticles, and liposomes, or encapsulating them in nanostructures, such as micelles or dendrimers. This helps protect the PS from degradation, improve their solubility and bioavailability, and enhance their photophysical and photochemical properties, ultimately improving their effectiveness in PACT. In this paper, recent studies focusing on strategies used to improve the delivery of porphyrin-based PS in PACT are reviewed.

The hydroisomerization of n-hexadecane over Pd/SAPOs bifunctional catalysts with different opening size: Features of the diffusion properties in pore channels and the metal-acid synergistic catalysis

In this work, SAPO-11, SAPO-31 and SAPO-41 with one-dimensional channels are synthesized hydrothermally by employing a di-n-butylamine (DBA) template, industrial silicon and aluminum sources, and the corresponding Pd/SAPOs bifunctional catalysts are prepared by loading 0.5 wt% Pd via the wet impregnation method. The diffusivity of n-hexadecane and 2-methylpentadecane in the micropores of different SAPOs is determined by molecular dynamics (MD) simulation, which indicates that the opening size has strong effects on the diffusion property of reactants and intermediates in the micropore channels. The calculated self-diffusion coefficients (Ds) of both n-hexadecane and 2-methylpentadecane based on MD simulation of three SAPOs decrease as SAPO-31 > SAPO-41 > SAPO-11, which is consistent with their minor axis size of micropores. The results of n-hexadecane hydroisomerization test indicate that the Pd/SAPO-31 catalyst shows the highest activity and iso‐hexadecane yield of 85.0% due to the significantly improved diffusion and favorable metal-acid balance. Different from Pd/SAPO-11 and Pd/SAPO-41, hydroisomerization over Pd/SAPO-31 occurs via the key lock mechanism, which leads to an increased multi-branched iso‐hexadecane proportion of 66.3% at the n-hexadecane conversion of 95.3%. The Pd/SAPO-31 catalyst is proven to be a highly effective bifunctional catalyst for the industrial production of bio-diesel with excellent low-temperature fluidity.

Manipulation of hydroisomerization performance on Pt/ZSM-23 by introducing Al2O3

ZSM-23 zeolite was successfully synthesized in a dual-template system, and ZSM-23-Al2O3 composites with different ratios were also prepared. The hydroisomerization performance of Pt/ZSM-23 catalyst was manipulated by introducing Al2O3, and the influence of Al2O3 on physicochemical properties was investigated by XRD, SEM, TEM, N2 physical adsorption-desorption and NH3-TPD characterizations. The results showed that Al2O3 improved the dispersion of Pt, significantly reduced the acid sites concentration of the catalyst, and regulated the metal-acid balance in quantitative. The suitable metal-acid balance concentration could improve the selectivity of isomers and suppress the cracking reactions. Meanwhile, Al2O3 dispersed the ZSM-23 grains, which improved the dispersion and increased the number of exposed pores in ZSM-23. Thus the diffusion efficiency of reactants and intermediates could be promoted and the isomer products selectivity could be improved. All composite catalysts showed high selectivity of isomer products, among which, Pt/(9Z-1Al) had the highest yield of isomer products due to its suitable metal-acid concentration balance, reached 60% at 340 °C, which was a significant improvement compared with Pt/ZSM-23 (42%). When the reaction temperature was lower than 310 °C, the pore mouth mechanism dominated in Pt/ZSM-23, while the key-lock mechanism was significantly strengthened at higher reaction temperature. After the introduction of Al2O3, more adjacent pores in ZSM-23 were exposed and the key-lock mechanism became the domination, which led to a large number of 7/8Me-C15 isomers.

The final step of 40S ribosomal subunit maturation is controlled by a dual key lock.

Preventing premature interaction of pre-ribosomes with the translation apparatus is essential for translational accuracy. Hence, the final maturation step releasing functional 40S ribosomal subunits, namely processing of the 18S ribosomal RNA 3' end, is safeguarded by the protein DIM2, which both interacts with the endoribonuclease NOB1 and masks the rRNA cleavage site. To elucidate the control mechanism that unlocks NOB1 activity, we performed cryo-electron microscopy analysis of late human pre-40S particles purified using a catalytically inactive form of the ATPase RIO1. These structures, together with in vivo and in vitro functional analyses, support a model in which ATP-loaded RIO1 cooperates with ribosomal protein RPS26/eS26 to displace DIM2 from the 18S rRNA 3' end, thereby triggering final cleavage by NOB1; release of ADP then leads to RIO1 dissociation from the 40S subunit. This dual key lock mechanism requiring RIO1 and RPS26 guarantees the precise timing of pre-40S particle conversion into translation-competent ribosomal subunits.

Hydroisomerization of Biomass Derived n-Hexadecane Towards Diesel Pool: Effect of Selective Removal External Surface Sites from Pt/ZSM-22

Abstract Influence of dealumination of zeolite ZSM-22 (Si/Al ratio of 45) by treating it with oxalic acid on its catalytic performance in n-hexadecane hydroisomerization reaction was studied. This reaction is an attempt in the direction of green and sustainable source of diesel via improving the cold-flow properties of deoxygenated vegetable oils. Pt (0.5 wt%) on ZSM-22 treated with 1 M oxalic acid afforded highest yields of the mono-branched paraffins. This improved is attributed to selective removal of active sites on external surface of zeolite crystals (responsible for undesired cracking reactions) using the bulkier dealuminating agent, oxalic acid. Thus, pore-mouth key-lock mechanism was brought to play the role to cause high selectivity to mono-branched isomers. Preferential external site deactivation was inferred from mesitylene cracking results. Effects of operating parameters such as temperature, and space velocity on product distribution also were studied. Also, kinetics of the reactions involved too has been in brief reported.

Particle selection through topographic templates in nematic colloids.

Liquid crystal colloids have been proposed as suitable candidates for responsive photonic crystals. Large scale growth of such colloidal systems is, however, a challenge and recently template-assisted assembly has been proposed to guide the growth of colloidal crystals, with controlled symmetries, in nematic liquid crystals. Known for their long-range anisotropic interactions, these colloidal systems are stabilized typically at the center of the cells due to strong particle-wall repulsion from the confining substrates. This behaviour is dramatically changed in the presence of topographic patterning. Here we propose the use of topographic modulation of surfaces to select and localize particles in nematic colloids. By considering convex and concave deformations of one of the confining surfaces we show that the colloid-flat surface repulsion may be enhanced or switched into an attraction. In particular, we find that when the colloidal particles have the same anchoring conditions as the patterned surfaces, they are strongly attracted to concave dimples, while if they exhibit different anchoring conditions they are pinned at the top of convex protrusions. Although dominated by elastic interactions the first mechanism is reminiscent of the depletion induced attraction or of the key-lock mechanism, while the second is specific to liquid crystal colloids. These long-ranged, highly tunable, surface-colloid interactions contribute to the development of template-assisted assembly of large colloidal crystals, with well defined symmetries, as required for applications.

New insights on the interface between metal oxide and biosystem.

The interface between titanium dioxide and biological solution is relevant for the bioactivity of titanium implants. Adhesion phenomena between inorganic solids are of general interest for mineralization and bone formation processes. Such interfaces are complex systems with many constituents including the hydroxylated metal oxide support, hydrocarbon contamination, ionic water solution and a variety of biopolymers. Our computational methods comprise classical molecular dynamics with around 106 atoms in the 10-100 ns range and ab initio molecular dynamics wit 100-200 atoms for some ps. • Electronic structure calculations show that even very thin layers of TiO2 on Ti metal may be commensurate and crystalline [1]. A variety of smooth and rough surfaces are implemented in force field simulations. • The oxide is hydroxylated and its surface charge density correlates with the pH-value. The highly hydrophilic TiO2 is in practice screened by hydrocarbons, which may enhance inflammatory complications of implants [2]. Simulations on the nature of this contamination are presented. • Sequence specific protein adsorption on inorganic surfaces was found in several experiments on inorganic surfaces, even though no key-lock mechanism is conceivable. We propose two effects [3]: (i) Contacts of single amino acid side chains to local charges in the surface have rupture energies, which sensitively depend on the electrostatics. The adhesion of appropriate double contacts is very strong exceeding simple hydrogen bonding. (ii) Soft motifs of proteins easier attach to the surface than rigid helices or strands. • Close to solids water has an ordered structure, which only slightly depends on the surface charge density. These layers hinder protein adsorption. A major difference to the bulk is the reduced water mobility there.

Impact of cationic surfactant chain length during SAPO-11 molecular sieve synthesis on structure, acidity, and n-octane isomerization to di-methyl hexanes

The structure, acidity, and n-octane di-branched isomerization of SAPO-11 synthesized with surfactants of different chain lengths in water–propanol system were investigated. The results showed that with the increasing chain length of surfactants, the crystallite size of SAPO-11 firstly decreased and then increased, but the external surface area and the active B acid sites of SAPO-11 firstly increased and then decreased. The smallest crystallite, the highest external surface area, and the most B acid sites were obtained simultaneously with the surfactant of 12 carbon atoms. The isomerization results of n-octane indicated that among the series Pt/SAPO-11 catalysts, the catalyst with DoTAB-directed SAPO-11 as support had the highest selectivity to di-branched isomers and the lowest cracking selectivity due to the largest external surface area that created more active sites to promote the formation of di-branched isomers by the key-lock mechanism and improve the diffusion of intermediates and products for reducing cracking reactions.

Three-Dimensional Morphology of Iron Oxide Nanoparticles with Reactive Concave Surfaces. A Compressed Sensing-Electron Tomography (CS-ET) Approach

In this paper, we apply electron tomography (ET) to the study of the three-dimensional (3D) morphology of iron oxide nanoparticles (NPs) with reactive concave surfaces. The ability to determine quantitatively the volume and shape of the NP concavity is essential for understanding the key-lock mechanism responsible for the destabilization of gold nanocrystals within the iron oxide NP concavity. We show that quantitative ET is enhanced greatly by the application of compressed sensing (CS) techniques to the tomographic reconstruction. High-fidelity tomograms using a new CS-ET algorithm reveal with clarity the concavities of the particle and enable 3D nanometrology studies to be undertaken with confidence. In addition, the robust performance of the CS-ET algorithm with undersampled data should allow rapid progress with time-resolved 3D nanoscale studies, 3D atomic resolution imaging, and cryo-tomography of nanoscale cellular structures.

A novel key–lock mechanism for inactivating amino acid neurotransmitters during transit across extracellular space

There are two kinds of neurotransmissions that occur in brain. One is neuron to neuron at synapses, and the other is neuron to glia via extracellular fluid (ECF), both of which are important for maintenance of proper neuronal functioning. For neuron to neuron communications, several potent amino acid neurotransmitters are used within the confines of synaptic space. However, their presence at elevated concentrations in extra-synaptic space could be detrimental to well organized neuronal functioning. The significance of the synthesis and release of N-acetylaspartylglutamate (NAAG) by neurons has long been a puzzle since glutamate (Glu) itself is the "key" that can interact with all Glu receptors on membranes of all cells. Nonetheless, neurons synthesize this acetylated dipeptide, which cannot be catabolized by neurons, and release it to ECF where its specific physiological target is the Glu metabotropic receptor 3 on the surface of astrocytes. Since Glu is excitotoxic at elevated concentrations, it is proposed that formation and release of NAAG by neurons allows large quantities of Glu to be transported in ECF without the risk of injurious excitotoxic effects. The metabolic mechanism used by neurons is a key-lock system to detoxify Glu during its intercellular transit. This is accomplished by first synthesizing N-acetylaspartate (NAA), and then joining this molecule via a peptide bond to Glu. In this paper, a hypothesis is presented that neurons synthesize a variety of relatively nontoxic peptides and peptide derivatives, including NAA, NAAG, homocarnosine (gamma-aminobutyrylhistidine) and carnosine (beta-alanylhistidine) from potent excitatory and inhibitory amino acids for the purpose of releasing them to ECF to function as cell-specific neuron-to-glia neurotransmitters.

A pharmaco-EEG study on antipsychotic drugs in healthy volunteers

Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle). We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle. Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands. Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1. The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics.

Effect of roughness on particle adhesion in aqueous solutions: A study of Saccharomyces cerevisiae and a silica particle

An atomic force microscope (AFM) has been used to quantify the adhesion of living cells Saccharomyces cerevisiae on three different silica surfaces with defined roughness. The effects of support roughness on the adhesion forces of a smooth silica particle were studied in addition. A living single cell was immobilized at the apex of a tipless AFM cantilever using a key–lock mechanism. Adhesion was quantified from the force–distance data measured on a smooth silica substrate and two substrates coated with hydrophilic monodisperse silica particles with 110 and 240 nm in diameter to study the effect of roughness on particle adhesion. The AFM technique gives unique insight into the primary colonization event of biofilm formation. The new knowledge helps substantially to design surface coatings relevant for biotechnology, medicine and dentistry.

Key-lock mechanism in nematic colloidal dispersions.

We consider the interaction between two-dimensional nematic colloids and planar or sculpted walls. The elastic interaction between colloidal disks and flat walls, with homeotropic boundary conditions, is always repulsive. These repulsions may be turned into strong attractions at structured or sculpted walls, with cavities that match closely the shape and size of the colloids. This key-lock mechanism is analyzed in detail for colloidal disks and spherocylindrical cavities of various length to depth ratios, by minimizing the Landau-de Gennes free energy functional of the nematic orientational order parameter. We find that the attractions occur only for walls with cavities within a small range of the colloidal size and a narrow range of orientations with respect to the cavity's symmetry axis.

Key-lock pair mechanism for access control using tribes of Farey fractions

We propose a new single key-lock mechanism based on the concept of an access control matrix. In this system, each file is given a lock and each user is given a key and through simple operations on keys and locks the user access privilege can be revealed. We use Chinese Remainder theorem and tribes of Farey fractions in this method instead of the method based on Euler’s Theorem of Number Theory used by Chang [2]. An advantage of our method is the ease with which coding can be done for the locking mechanism and for the much larger number of users and files.