High-throughput screening (HTS) is an integral part of early drug discovery. Herein, we focused on those small molecules in a screening collection that have never shown biological activity despite having been exhaustively tested in HTS assays. These compounds are referred to as 'dark chemical matter' (DCM). We quantified DCM, validated it in quality control experiments, described its physicochemical properties and mapped it into chemical space. Through analysis of prospective reporter-gene assay, gene expression and yeast chemogenomics experiments, we evaluated the potential of DCM to show biological activity in future screens. We demonstrated that, despite the apparent lack of activity, occasionally these compounds can result in potent hits with unique activity and clean safety profiles, which makes them valuable starting points for lead optimization efforts. Among the identified DCM hits was a new antifungal chemotype with strong activity against the pathogen Cryptococcus neoformans but little activity at targets relevant to human safety.
Quality control results. For 623 compound structures identified as dark chemical matter in the Novartis data set, results from our quality control experiments are reported. Purity, identity, concentration, and comments about how to interpret the observed data for special cases (e.g. highly fluorinated compounds) are given. Compounds are represented by InChI keys and SMLES strings. (XLSX 54 kb)
Dark chemical matter Bayes classifier. We attach the naive Bayes model trained on the PubChem data set as Pipeline Pilot component (xml file). This component returns a dark matter score for each molecular data record sent to it. (XML 2227 kb)
Everything you hear, see, smell, taste, and touch involves chemistry and chemicals (matter). And hearing, seeing, tasting, and touching all involve intricate series of chemical reactions and interactions in your body. With such an enormous range of topics, it is essential to know about chemistry at some level to understand the world around us.
Although there are countless types of matter all around us, this complexity is composed of various combinations of some 100 chemical elements. The names of some of these elements will be familiar to almost everyone. Elements such as hydrogen, chlorine, silver, and copper are part of our everyday knowledge. Far fewer people have heard of selenium or rubidium or hassium.
And so it is with chemistry, understanding the basic properties of matter and learning how to predict and explain how they change when they react to form new substances is what chemistry and chemists are all about.
Matter is anything that takes up space and can be weighed. In other words, matter has volume and mass. There are many different substances, or types of matter, in the universe. Chemists describe matter based on both physical characteristics, such as color or mass, and chemical characteristics, such as how one type of matter interacts with another type of matter. There are many ways to describe and classify matter.
Fundamentally, matter is composed of elementary particles called quarks and leptons, both of which are considered elementary particles in that they aren't made up of smaller units of matter. Quarks -- groups of subatomic particles that interact by means of a strong force -- combine into protons and neutrons. Leptons -- groups of subatomic particles that respond to weaker forces -- belong to a class of elementary particles that includes electrons.
Atoms are the building blocks of matter. A combination of atoms forms a molecule. Large groups of atoms and molecules form the bulk matter of day-to-day life in the physical world. There are more than 100 different kinds of atoms listed in the periodic table, with each kind constituting a unique chemical element.
All matter consists of atoms, which, in turn, consist of protons, neutrons and electrons. Both protons and neutrons are located in the nucleus, which is at the center of an atom. Protons are positively charged particles, while neutrons are neutrally charged. Electrons are negatively charged, and they exist in orbitals surrounding the nucleus.
Depending on temperature and some other factors, matter can exist in several states. The three most common states are known as solid, liquid and gas. A single element or compound of matter might exist in more than one state, depending on the temperature and pressure conditions. One common example is water, which can exist in solid, liquid and gaseous forms and can be readily observed in each of these states.
The state of matter can be changed by heating or cooling it or by changing the pressure conditions on it. When a material changes state, its molecules behave differently but don't break apart. Since they remain essentially the same, they don't form a different material but simply change the state of the existing material.
All solids have a definite shape, mass and volume, which prevents them from conforming to the shape and volume of a container where they are kept. This is one of the properties that differentiates solid matter from liquid matter.
Unlike solids, particles in liquid matter are more loosely packed. This enables them to flow around each other, which gives the liquid an indefinite shape. It is this lack of a specific shape that enables liquids to conform to the shape of containers. Liquids are also less dense than solids. Both solids and liquids are difficult to compress.
In unconfined gaseous matter, particles are spread out indefinitely since they have a lot of space between them. This space is also why atoms in gases have large vibrations, and particles have high kinetic energy.
In some situations, matter is converted into energy by atomic reactions, also known as nuclear reactions. Nuclear reactions involve changes in the nuclei of atoms. This makes them different from normal chemical reactions.
Melting occurs when heat is applied to a solid. The solid matter's particles start to vibrate rapidly and move apart from each other. This process increases the distance between them. Once specific temperature and pressure conditions are achieved, the solid transforms into a liquid. This specific point is known as the solid's melting point.
Similarly, the proton has an antimatter twin called an antiproton, and the neutron has an antimatter twin called an antineutron. Einstein's formula states that, if a particle of matter encounters its antiparticle, both are converted entirely to energy. In this case, m is the combined mass of the particle and the antiparticle.
Small amounts of antimatter have been isolated in laboratory conditions, but no one has yet succeeded in creating a controlled matter/antimatter reaction or even an uncontrolled reaction of significant size.
Main outcome measures: Estimates of gray and white matter concentrations for choline-containing compounds (Cho), creatine plus phosphocreatine, N-acetylaspartate (NAA), and myo-inositol (mI). Transverse relaxation times for Cho, creatine plus phosphocreatine, and NAA expressed relative to control subjects with TD were examined to evaluate tissue compactness.
Results: The children with ASD demonstrated decreased gray matter concentrations of Cho (P < .001), creatine plus phosphocreatine (P = .02), NAA (P = .02), and mI (P = .008) compared with children with TD. Gray matter Cho transverse relaxation was also prolonged for the ASD sample compared with the TD group (P = .01). The children with ASD demonstrated significantly decreased levels of Cho (P = .04) and mI (P = .008) and trend-level NAA (P = .09) in gray matter compared with the DD group. For white matter, both children with ASD and children with DD showed a similar pattern of NAA and mI level decreases (for children with ASD vs children with TD: NAA, P = .03; mI, P = .04; for children with DD vs children with TD, NAA, P = .03; mI, P = .07). In several analyses, cerebral volume contributed significantly as a covariate.
Conclusions: Reduced gray matter chemical concentrations and altered Cho transverse relaxation, in a pattern distinct from that in children with DD, suggest decreased cellularity, or density, at this early time point in ASD. Possibly reflecting shared developmental features, white matter results were common to ASD and DD groups. The relationship between cerebral volume and neurochemistry at this early time point may indicate processes related to unit scaling.
All matter is made from atoms. Every substance (oxygen, lead, silver, neon ...) has a unique number of protons, neutrons, and electrons.Oxygen, for example, has 8 protons, 8 neutrons, and 8 electrons.Hydrogen has 1 proton and 1 electron.Individual atoms cancombine with other atoms to form molecules.Water molecules contain two atoms of hydrogen H and one atom of oxygen Oand is chemically called H2O.Oxygen andnitrogen are the major components ofairand occur in nature asdiatomic (two atom) molecules.Regardless of the type of molecule, matter normallyexists as either a solid, a liquid, or a gas.We call this property of matter the phase of the matter.The three normal phases of matter have unique characteristics which are listed on theslide.
Any substance can occur in any phase. Under standard atmospheric conditions,water exists as a liquid. But if we lower thetemperature below 0 degrees Celsius, or 32 degrees Fahrenheit, water changes itsphase into a solid called ice.Similarly, if weheat a volume of water above 100 degrees Celsius, or 212 degrees Fahrenheit,water changes its phase into a gas called water vapor.Changes in the phase of matter are physical changes, notchemical changes. A molecule of water vapor has the same chemicalcomposition, H2O, as a molecule of liquid water or a moleculeof ice.
The three normal phases of matter listed on the slide have been known for many years and studied in physics and chemistry classes. In recent times, we have begun tostudy matter at the very high temperatures and pressures which typically occur on the Sun, or during re-entry from space. Under these conditions,the atoms themselves begin to break down; electrons are stripped from their orbit around the nucleus leaving a positively charged ionbehind. The resulting mixture of neutral atoms, free electrons, and chargedions is called a plasma. A plasma has some unique qualities thatcauses scientists to label it a "fourth phase" of matter. A plasma isa fluid, like a liquid or gas, but because of the charged particles presentin a plasma, it responds to and generates electro-magnetic forces. Thereare fluid dynamic equations, called the Boltzman equations, which includethe electro-magnetic forces with the normal fluid forces of the Navier-Stokesequations. NASA is currently doing research into the use of plasmas for an ion propulsion system. 2b1af7f3a8