Abstract

A molecular machine is a group of molecular components that are able to produce quasi-mechanical movements when exposed to specific stimuli. There are three broad divisions of the molecular machines, namely natural or biological, synthetic, and natural-synthetic hybrid machines. Biological motors convert chemical energy to produce linear or rotary motion as well as controlling many biological functions. Examples of the linear motions are proteins, muscle contraction, intracellular transport, signal transduction, ATP synthase, membrane translocation proteins and the flagella motor. The rotary motor example of biological molecular machines is the synthesis and hydrolysis of ATP. Synthetic molecular machine includes motors, propellers, switches, shuttles, tweezers, sensors, logic gates. Natural-synthetic hybrid systems are mechanical motor such as those inspired from DNA-based structures.

1. Types of Molecular Machines

Biological motor is a natural device in a molecular scale that is able to convert a definite amount of chemical energy to produce linear or rotary motion as well as controlling many biological functions.

The benefit of biological motors is its performance of complex functions, while the major disadvantage is their instability against the environmental operation conditions ¹. Understanding biological systems provides many ideas to design effective nanometric-constructions which are able to operate molecular machines ². Scientists hope to use biological machines in nanomedicine field to detect and destroy cancer cells ^{3, 4} and introducing nanorobots into the body to detect any failure.

There are two types of the output motions obtained from a biological motor, namely linear and rotary motions. Examples of the linear motions are proteins, contraction of muscles, transportation between cells, signal transduction, synthase of ATP ^{2, 5, 6, 7}, membrane translocation proteins, the bacterial flagella motor ⁸, and proteins that can chelate and release objects through chemo-mechanical motion ^{2, 6}. The rotary motor example is the synthesis and hydrolysis of ATP ^{2, 5, 6, 7}.

There are several protein-based biological molecular machines have constructed for example but not restricted to the following:

a) Myosin, the protein molecule responsible for contraction of muscles,

b) Kinesin, which is responsible for the cargo movement within cells apart from the nucleus along microtubules, and

c) Dynein, which produces the axonemal beating of motile cilia and flagella. These proteins are far more complicated than any artificial molecular machines.

d) Motile cilia are a molecular machine constituted of more than 600 kind of proteins in molecular complexones ⁹.

e) Ribosome: It is a complex molecular machine in all living cells serving as the protein synthesis (translation) sit. The ribosome task is to thread amino acids in an identified sequence by messenger RNA (mRNA) molecules. Ribosomes consist of two princible components, namely the small (for reading the RNA), and the large ribosomal (for conjugating amino acids to form a polypeptide chain. Each component is composed of one or more ribosomal RNA (rRNA) molecules and different ribosomal proteins.

Biological materials such as DNA-based structures have been inspired to construct various mechanical biological motors ^{10, 11, 12} to construct sensors, actuators and transporters ^{13, 14}. The most important benefit of the synthetic molecular machine is that they can endure broader range of rigor conditions than biological machines. From a synthetic view, there are seven essential types of molecular machines as follow:

They are molecules that are able to make uni-directional rotation when gained an external energy (input). A number of molecular motors have been synthesized else powered by light or chemically when reacted with other molecules.

Molecular propeller (Figure 1) is a molecule that can push or propel fluids meanwhile its rotating, due to it is designed analogous to commercial propellers ^{15, 16}. Really, it has several blades, in the angstromic-scale, arranged at a definite pitch angle around its nano-sized shaft.

It is a molecule that can be shifted between more than one stable state reversibly due to changes in pH, light, temperature, an electric current, etc. When the stimuli effect is removed, it liberates energy to the system. Furthermore, switches cannot reuse the released chemical energy for frequent and progressive driving their systems apart from equilibrium state but a molecular motor can do this task.

As shown in Figure 2, a molecular machine consisted of an azo-benzene molecule can be switched between cis and trans isomers in a completely controlled manner in frequent mechanical cycles. Since the trans form has massive groups on opposite sides of the π bond while the cis has massive groups on the same side, the massive groups can be turned closer together or further apart by switching between the cis and trans isomers. This switching process can be controlled by using light of two different wavelengths, one to go transfrom cis to trans and the other to reverse the process.

The molecular shuttle or rotaxane (Figure 3) is construction consisting of two components, namely dumbbell-like molecule and macro-cycle. The dumbbell is threaded through the macro-cycle (Figure 3, Figure 4a and Figure 4b). The ends of the dumbbell are bigger than the internal diameter of the macro-cycle and prevent dissociation of the components. This molecular device can shuttle molecules or ions from one station to another. The macro-cycle can move between two stations along the dumbbell axle.

The molecular shuttle shown in Figure 4c is drawn as a molecular thread consisted of an ethylene glycol chain carrying two arene groups (the stations). The terminal units (the stoppers) on this wire are triisopropylsilyl groups. The bead is a tetracationic cyclophane based on two bipyridine groups and two para-phenylene groups. The bead is locked to one of the stations by pi-pi interactions but since the activation energy for migration from one station to the other one is only 13 kcal/mol, the bead shuttles between them. We can note from Figure 4a and Figure 4b that the stoppers are obstacles of slipping the bead from the thread.

It is a molecule capable of catching objects in its open cavity between its own double arms (Figure 5) using non-covalent bonds such as hydrogen bonds, metal coordination, hydrophobic forces, van der Waals forces, π interactions, or electrostatic forcess. The famous molecular tweezers are inspired from DNA natural machine.

It is a molecule that affected by an analyte to produce a measurable signal ²¹. Early constructions of them are crown ethers with high affinity to N⁺ but not for K⁺. This system can be used for metal detection as pH indicators by forming complexones modified by grafting certain molecular groups sensitive to metals.

Through a logic operation, the molecular logic gate molecule can produces a single output when responded to one or more logic inputs and produces a logic output. Differing from the molecular sensor, the molecular logic gate will only output when a all the inputs are present.

Molecular logic gates depend on chemical input signals and with spectroscopic output. As indicated from Figure 6a and Figure 6b ²², the compound presented is consisted of two parts: 1) top receptor containing four carboxylic acid anion groups able to conjugate calcium, and 2) the bottom section that contains a tertiary amino group also able to bind H⁺.

For the chemical system presented at Figure 6a, the logic gate molecular machine operates as follows: Without any chemical input of Ca²⁺ or H⁺, the chromophore shows a maximum absorbance in ultra violet/visible light range at 390 nm. When Ca²⁺ is introduced, a blue shift is occurred and the absorbance at 390 nm is decreased. In addition, the addition of H⁺ causes a red shift and when Ca²⁺ and H⁺ are present in the water, absorbance in UV/VIS region at the original 390 nm is shown.

For the chemical system presented at Figure 6b, fluorescence only occurred when both Ca²⁺ and H⁺ are available (the output is “1”) that prevent transferring of electrons induced by light (photo-inducion). In the absence of one or both cations, fluorescence is stopped by the PET, from either the nitrogen or the oxygen atoms or both, to the anthracenyl group. When both receptors chelate to Ca²⁺ and H⁺ respectively, both PET channels are shut off.

They are mechanical motor such as those inspired from DNA-based structures ^{10, 11, 12}.

A light-actuated nanovalve was constructed to control photochemical transportation of solutes through a bilayer lipid solution. This valve is consisted of a channel protein grafted with spiropyran switch which is a photochemically active ²³. It acts as a valve control for the 3 nm channel and can be opened and closed by using UV and visible light, respectively. This system allows to external photo-control of the transportion process through the channel.

When UV energy is focused on the protein, it is converted from its neutral hydrophobic state to a charged polar state. This change in hydrophobicity leads to opening of the channel. In addition, this molecular vale can be closed by using visible light (Figure 7).

2. Molecular Motions

The biological motor is a device that imparts motion by converting a chemical fuel, thermal or light, into kinetic energy under controlled conditions ²⁴. Frequently, biosystems depends on adenosine triphosphate (ATP) as their energy source ⁵.

To build synthetic molecular rotary motors, three concepts must be considered: 1) repetitive 360° rotation, 2) energy consumption, and 3) control over directionality.

A major difficulty for artificial molecular machines is the controlling of their operation and directionality. Asymmetry is a stone key to the successful design and operation of directionally controlled molecular machines. In terms of machine size, bigger devices are not always better. Indeed, smaller molecular devices offer clear benefits comparing to larger assemblies. Finally, several molecular motors should be able to operate cooperatively to translate molecular movement to macroscopic levels.

Designs of molecular rotor systems depending on thermal random brownian motion are available widely, ^{25, 26}. In contrast to ordinary motors, in which energy input induces motion, biological motors consume energy to restrict brownian motion selectively ²⁷. In a biological system, the random-motion is utilized to obtain net directional movement in linear or rotary motions progressively and not reversibly

Examining Figure 8b, the upper and lower carborane can ligand to a nickel ion. Oxidation and reduction of the nickel center through Ni³⁺ / Ni⁴⁺ ions can rotate the upper ligand in relation to the lower ligand, changing the relative position of the alkyl groups (R₁–R₄) attached to the carborane ligands. Although the most investigations have worked on aqueous systems, recent works on crystalline molecular rotors ^{29, 30} was done with fast free rotation. For instance, a fast rotary motion around a carbon-carbon bond was achieved with uncontrolled directionality of the rotation ³⁰. It is worth to mention that molecular machines and are not rigid, but changable in their shape continuously. Accordingly, design of artificial systems must take the dynamics of molecular flexibility under consideration ³¹.

Although randomness of direction of the motion featured by these systems, good design must focus on the manner of controlling the rotary motion. For instance, in the carborane molecular rotors ²⁸ shown in Figure 8b, the unidirectionality of rotation might be obtained by grafting further massive groups to increase the asymmetry of the molecular machine. However, researches must restrict the brownian turbulence by immobilizing the molecular machines through membranes as well as on surfaces. In addition, design and synthesis of these machines must be large enough to overcome the brownian motion.

Multimetallic systems can be done by using two kinds of metals: 1) A catalyst to decompose of H₂O₂ that can be considered as a chemical fuel, and 2) a relatively inert metal to generate local gradients in O₂ concentration and/or surface tension. Accordingly, both metals help to generate propulsion stimulus leading to move the metallic object ^{32, 33} as shown in Figure 9.

There two techniques can be performed to produce a movement of an object: 1) Pressure from bubble formation, and 2) Oxygen gradients/surface

The size of the object determines the technique type ³⁴ as follow: 1) For objects having a size of >50 μm, the movement induced by oxygen release is related to the effect of bubble formation,

2) For particles <1 μm in size, we cannot distinct between the real particles motion brownian motion in the same environment.

3) Between 1 and 20 μm, particles motion is powered only by oxygen concentration gradients, while brownian motion and bubble formation had no effect on their motion ³⁵. The accurate control of the directionality in such systems is a hard task but possible. Some researchers succeeded in this task magnetically by using metallic rods made up of platinum-nickel-gold rods ³⁴. Furthermore, powering motion in molecular systems can be performed by chemical fuels such as hydrogen peroxide, pH and redox changes or by light ³⁶.

A modified molecular motor powered by phosgene as an internal chemical fuel was constructed. The motor was rotated unidirectional by “120°” around its carbon–carbon bond axle ³⁷. In addition, when using a sequence of chemical conversions as a system fuel, a 360°-unidirectional rotation was achieved ³⁸. Importantly, this highlights importance of accurate selection of chemical reagents that act as powering fuels to control the rotor movement. The next rotor example use four distinct stations to produce an unidirectional rotation. Within each station the rotor's brownian motion relative to the stator is restricted by structural features.

Based on Figure 10a, the molecular structure of the molecular motor driven by chemical energy is presented. The unidirectional movement along the ring is governed by sequential chemical and photochemical reactions (Figure 10b-d). At each stage, one ring prevents the reverse rotation of the other ring ensuring unidirectionality over the entire cycle ³⁹.

All the above mentioned-molecular motors convert chemical or light energy into either directional linear o rotary or linear motion operates in solution. Although brownian motion can be overcome by building micrometer-scaled devices, scientists tried to use another technique to overcome the brownian motion by immobilizing these machines on a surface without losing functionality when immobilized. Anchoring and addressing molecular machines on surfaces is a key stone to the successful interfacing of nanomechanical systems with the macroscopic scale ²⁴.

3. Conclusions

• There are three broad divisions of the molecular machines, namely natural or biological, synthetic, and natural-synthetic hybrid machines.

• Biological motors convert chemical energy to produce linear or rotary motion as well as controlling many biological functions.

• Examples of the linear motions are proteins, muscle contraction, intracellular transport, signal transduction, ATP synthase, membrane translocation proteins and the flagella motor.

• The rotary motor example of biological molecular machines is the synthesis and hydrolysis of ATP.

• Synthetic molecular machine includes motors, propellers, switches, shuttles, tweezers, sensors, logic gates. Natural-synthetic hybrid systems are mechanical motor such as those inspired from DNA-based structures.

A phosgene-molecular motor was constructed to rotat unidirectional by “120°” around its carbon–carbon bond axle.

• Using a sequence of chemical conversions as a system fuel, a 360°-unidirectional rotation was achieved which highlights the importance of accurate selection of chemical reagents that act as powering fuels to control the rotor movement.

• To overcome the brownian motion, scientists immobilized molecular machines on a surface without losing functionality when immobilized.

References